THE PREPARATION AND REACTIONS OF KETONES CONTAINING THE DINEOPENTYLCARBINYL GROUP

DOCTORAL DISSERTATION SERIES
mg me itm r d in m J fttAckm o f Kdonci
Ctrlmm i
AUTHOR
tBMeirPiiy! Group
Chirks Turn Lester
UNIVERSITY.
DATE
M
fi. S id e College
DECREE
PUBLICATION NO;
li1 a *
'I1'I1'I1
# UNIVERSITY MICROFILMS
ANN ARBOR • M ICHIGAN
THE PENNSYLVANIA STATE COLLS03
The Graduate School
Department of Chemistry
The Preparation and Reactions of Ketones
Containing the Dlneopentylearbinyl Group
by
Charles Turner Lester
Submitted In p a r t i a l fu lfillm e n t
of the requirements fo r the degree of
DOCTOR OP PHILOSOPHY
August 1941
/
Approved
Organic Chemistry
Head of Department
of Chemistry
1941
Acknowledgme nt
The author wiahea to express h is g ratitu d e to
Dr* F. C. Whitmore, d irecto r of th is research, fo r his
unfailing
I n te r e s t, patience, and timely suggestions;
to P rof. H* 5* Marker for many valuable techniques; to
C* E* Lewis for h is help with active hydrogen determina­
tio n s ; to D. O. Clarke fo r hie assistance In various
phases of th is work*
Table of Contents
page
Introduction • • • • • •
H isto ric a l
.
.
.
.............................................
.
1
...............................................................................................
7
Discussion ................................................................
.
.
. .
•• • • • . . . .
15
................................................................................................22
Experimental
I . D escription of
Apparatus U s e d ..................................................22
A. Columns U s e d .................................. . . . . . . . .
B• Zerewitlnow
22
D e te r m in a tio n s ............................................22
I I . Preparation of S ta rtin g M aterials
..................................
22
A. Preparation of Dineopentylacetlc Acid • • •
22
1. Oxidation of Dlneopentylethylene with
Chromic Oxide and Acetio Acid . . • . .
22
2. Oxidation of Dlneopentylethylene with
Chromic Oxide and Acetic Anhydride
• •
24
B. Preparation of Dineopentylacetyl Chloride
•
25
......................
27
1. Preparation of Methylm&gnesium Bromide.
27
2. Preparation of Ethylmagneslum Bromide •
28
C. Preparation
o f Orignard Reagents
3. Preparation of iso-Propylm&gnesium
Brom ide...........................................................................................28
4. Preparation of lso-Butylmagneslum
Bromide . . . . . .
28
5. Preparation of t-Butylmagneslum Bromide
28
6.
Preparation of Phenylmagneslum Bromide.
29
7. Preparation of p-Tolylmagneslum Bromide
29
8.
29
Preparation of o-Tolylmagneslum Bromide
page
I I I . R e a c tio n s ........................................................................................
30
A. Addition o f Dineopentylacetyl Chloride to
M
ethy lmagne slum Brom ide.........................................................30
B. Addition of Methylmagnealum Bromide to
Dineopentylacetyl Chloride
........................................
31
C. Preparation of Dlneopentyloarbinyl Methyl
Ketone . . . . . . . .
.
34
D. Reactions of Dlneopentyloarbinyl Methyl
Ketone
* .................................................
35
.
1. Preparation of Dineopentylcarbinylm e t h y lc a r b l n o l...........................
35
2. Reduction of Dlneopentyloarbinyl Methyl
Ketone with Sodium and Bthanol
• • • •
36
3. Reaction of Dlneopentyloarbinyl Methyl
Ketone with Aluminum lso-Propylate
• •
38
4. The Reaction of Dlneopentyloarbinyl
Methyl Ketone with Grignard Reagents.
40
•
a. Reaction of Dlneopentyloarbinyl
Methyl Ketone with iao-Propylmagneslum Bromide...................................................40
b* Reaotlon of Dlneopentyloarbinyl
Methyl Ketone with iao-Butylmagnesium Bromide • . . • • • • • •
41
c. Reaction of Dlneopentyloarbinyl
Methyl Ketone with t-Butylmagneslum
Chlor i d s .........................................................................42
5. Reaction of Dlneopentyloarbinyl Methyl
Ketone with Sodium Hypobromite.............................43
6.
Preparation of the Monobromoketone
7. Reactions of the Monobromoketone
• •
. . .
45
46
a. Reaotlon of the Monobromoketone
with Zinc and Acetic A c id .............................46
b. Reaction of the Monobromoketone
with P y r i d i n e ..............................................................47
o. Reaotlon of the Monobromoketone
with Aloohollo PotassiumHydroxide*
47
d. Reaotlon of the Monobromoketone
with Potassium Acetate - Acetic
A o l d ..........................................................................49
8 . The Reaction o f Dlneopentyloarbinyl
Methyl Ketone with SodiumHydroxide
.
.
50
9. Attempted Alkyl&tlon of Dineopentylcarblnyl Methyl Ketone
.......................................
50
10. Attempted Oxidation of Dlneopentylcarblnyl Methyl Ketone
.......................................
51
11. Reaction o f Dlneopentyloarbinyl Methyl
Ketone with Sodium Hypolodite • • • • •
52
B. The Reactions of the Bromomagneslum Bnolate
of Dlneopentyloarbinyl Methyl Ketone. . . .
53
1. The Gilman Grignard T e s t ........................................53
2. The Preparation o f Acetyldlneopentyl.........................................................53
ace tylme thane
3. The Preparation of Benzoyldineopentylacetylose thane
...........................
54
4. Preparation of Methyl-t-butylneopentylacetyldlneopentylaoetylme thane.............................55
5. Preparation of Phenyl- (beta-keto-gansna,
gamma-dineopentylpropylj-carbinol . . .
6.
Preparation of Diphenyl-(beta-ketogamma,gaxnma-dlneopentylp:ropyl)-oarblnol
56
57
7. Preparation of beta-Keto-gamma,gammadineopentyl-butyric Acid..............................................58
8 . Attempted Alkylatlon of the Enolate of
Dlneopentyloarbinyl Methyl Ketone . . .
59
F. Preparation o f Dlneopentyloarbinyl Ethyl
K e t o n e ....................................................................................................60
page
G. Rea c tio n s or Dlneopentyloarbinyl Ethyl
Kstono
• • • • .............................................
63
1 . Reaotlon of Dlneopentyloarbinyl Ethyl
Ketone with Sodium Hydroxide. . . .
•.
63
2 . P reparation of Monobromoketone....................64
3 • Reaction of D lneopentyloarbinyl Ethyl
Ketone with Sodium Hypobromlte....................66
4 . Reaction of Dlneopentyloarbinyl Bthyl
Ketone with t-B uty lmagne slum Chloride •
H. Reactions of the Bromomagneslum Snolate of
Dlneopentyloarbinyl Ethyl Ketone • •
• • •
1 . The Oilman Grlgnard Test
. . . . . . .
67
68
68
2 . Preparation o f l p1 -B is-(dlneopentyla c ety l)-eth an e
.
..........................................................68
3 . Preparation of alpha-Me thy 1-b eta-k eto gamna, gamma-dlneopentylbutyrlc Acid •
4 . P reparation o f 1-D ineopentylacetyl-lbenzoyl-ethane
............................
• 69
70
5. Preparation o f Phenyl-(alpha-methylb et a-ke to-gamma, gamma-dine open ty lp ro p y l)carb in o l
............................
71
6 . Preparation o f D iphenyl-(alpha-methyl-
beta-keto-gamma,gamma-dineopentylpr o p y l ) - c a r b i n o l ................................................................72
I.
Preparation of Dlneopentyloarbinyl Phenyl
Ke t o n e .......................................................................................................73
J.
Reactions of Dlneopentyloarbinyl Phenyl
Ketone
. . . . . . .
74
1. Attempted Bromlnation of Dineopentyloarbinyl Phenyl Ketone.....................................................74
2 . Attempted Oxidation of Dineopentyloarbinyl Phenyl Ketone.
.................................
75
3 . Reaction of Dlneopentyloarbinyl Phenyl
Ketone with Methy lmagne s ium Iodide. • •
76
Preparation of Dlneopentyloarbinyl o-Tolyl
Ketone
• ..............................................................................................78
Reactions of Dlneopentyloarbinyl o-Tolyl
K e t o n e ....................................................................................................79
1* Attempted Bromlnation of Dlneopentyloarblnyl o-Tolyl Ketone .......................................
79
2. Oxidation of Dlneopentyloarbinyl o-Tolyl
K e t o n e .........................................................................................79
Preparation of Dlneopentyloarbinyl p-Tolyl
K e t o n e ....................................................................................................81
Reactions of Dlneopentyloarbinyl p-Tolyl
K e t o n e ....................................................................................................81
1. Attempted Bromination of Dineopentylcarbinyl p -to ly l Ketone
........................................81
2* Oxidation of Dlneopentyloarbinyl p-Tolyl
K e t o n e ...................................................................... . . . 82
The Preparation of Dlneopentyloarbinylglyoxal
. . . . .
Reactions of 1 ,3-Diketones
................................
1. Alkylatlon of 1 ,3-Diketones
83
.
84
. . . . . .
84
a. The Methylation of Bis-(dineopentylacetyl) -me thane
...................................................34
b. The Attempted Ethylatlon of Bls(dineopentylacetyl)-methane
. . . .
85
c. The Methylation of 1 ,l-B is-(dineopentylacetyl)-ethane
..................................
86
d. The Attempted Ethylatlon of 1,1-Bis(dineopentylacetyl)-ethane. . . . .
86
e. The Methylation of Benzoyldineopentylacetylmethane .......................................
87
2. The Bromination of Bis-(dineopentyla c e ty l)-methane . . . . . . . . . . . .
87
page
3# Action of Sodium Hydroxide on 1,3Diketones .............................. . . . . . . . . .
88
Suggestions for Further In v e stig a tio n .............................................90
B ib lio g rap h y ..............................................................................................................92
Introduction
With the large q u a n tities of 1 ,1 -dlneopentylethylene
available in t h i s laboratory, i t
seemed possible th a t th is
m aterial could be used to synthesize other in te re s tin g
hydrocarbons.
The following se rie s of reactio n s offered
an apparently sloqple route for such a synthesis.
RgCsCHg
LO]^ RgCHCOGH
S0C1g ) RgCHCOCl
CHgMgBry
CH3
RgCHCOH(CH3 )g
RgCsC(CHs )g
(R*neopentyl, CHg-C—CHg-)
ch3
The f i r s t two reactions in th is series have been
thoroughly investigated in t h i s laboratory ( l)
no d if f ic u lty .
and offered
However, when dineopentylaoetyl chloride
reacts with methy lmagne slum bromide, there is no t e r t i a r y
alcohol formed, regardless of the excess of Orignard reagent
used,
a
careful examination of the reaction shows th a t the
acid chloride re a c ts with one equivalent of methylmagnesium
bromide to form the ketone, dlneopentyloarbinyl methyl
ketone.
This ketone, Instead of adding one equivalent of
the Grlgnard reagent, lib e ra te s one equivalent of methane
and forms the b*?omomagnesium enolate of the ketone:
RCOCl+CHgKgBr = RCOCH3
_CH5M
^ r >
> CH4 +(RC0 CH2)MgBr
CH3
CH3
e
The reaction of the methyl ketone is lik e th a t of aoetomesitylene (2)*
This reactio n i s termed enolization and is
a ttrib u te d to e te rio hindrance (2 )*
With e th y l, iso-propyl,
iso -b u ty l,
and t-b u ty l
Orignard reagents, dlneopentyloarbinyl methyl ketone under­
goes th is same type of reactio n :
RC0CH3+R *HgX a (RC0CH2 )MgX+R,H
(RSdineopentyloarbinyl; R♦■methyl,ethyl,iso-propyl,iso­
butyl, or t-b u ty l)
In each case the addition of water to the halomagneslum
enolate regenerates the ketone.
In many of i t s
other reactions dlneopentyloarbinyl
methyl ketone shows indications of a s te r io a lly hindered
carbonyl group.
I t Is hydrogenated only slowly even at
high temperature and p ressure; i t
is reduced by aluminum
iso-propylate only a fte r eight days of heating; to form a
2 , 4 -dlnitrophenylhydrazone derivative requires refluxlng
for fiv e weeks; with sodium hypobromite only two of the
methyl hydrogens are replaced by bromine; i t i s unaffected
by sodium hypoiodlte; and i s to ta lly r e s is ta n t to a lk a li
a fte r refluxing for ten days.
ever, i t
Like acetomesltylene, how­
read ily re a c ts with bromine ( 3 ) and is e a sily r e ­
duced with sodium and ethanol (4).
The bromomagnesium enolate of dlneopentyloarbinyl
methyl ketone gives reactio n products which indicate th a t
3
i t baa the stru c tu re of a tru# a n guard reag en t, RCOCHgHfiBr
(Rsdlneopentylearblnyl) •
With a c e ty l,
bensoyl, and dineo-
pentylaoetyl chlorides th e snolate gives tho corresponding
1 , 3-di ke ho no • t
RCOCHgJigBr-eR’C O C l « RCOCHs COR»
(Rsdl neopent y lo a rb in y l; R •smethyl, phenyl, or dineo­
pent yloarb in f 1 )
When oarton dioxide l a passed In to the enolate,
a beta-keto
aoid i s obtained:
RCOCHgMgBr-f G Og 5 RCOCHgCOOH.
(R=dlneopentyloarbinyl)
With bensaldehyde and bensophenone the enolate gives a keto
secondary and keto t e r t i a r y alcohol re sp e c tiv e ly :
RCOCHgMgBr+CgEgCHO
* RCOCH^CHOHC^g
RCOCH2MgBr+(C6 H5) 2CO S RCOCH2COH(CgH5 )2
(Rs di neope nt yla arb i n y l )
F inally, th e h r omoniagneslxim enolate give* a pos 1t i r e Oilman
te s t,
c h a ra c te ris tic of a tru e Orlgnard reagent (5) •
When dlneopentylacetyl chloride la tr e a te d with excess
ethylmagmeslum bromide,
reaotlon also re s u lts
th e e th y l ketone I s
obtained.
This
In the formation of the bromomagneslum
enolate by the action of the excess e f reag en t.
ketone rea cts w ith methyl,
eth y l,
The ethyl
suid t- b u ty l arignard
reagents In the same manner as the methyl ketone:
R C O C i^ C H ^ R *KcpC ■ RCOCH (C H a) HgX+R »H
4
(R-dlnaopentylcarbinyl; R*smethyl, eth y l, or t-b u ty l)
The bromomagnesium enolate undergoes a l l the reactions
indicated for the enolate or the methyl ketone.
The enollzation or the methyl and ethyl ketones orrers
an in te re s tin g problem.
Since the dlneopentyloarbinyl
group contains a t e r t i a r y hydrogen, th is hydrogen could
conceivably be the one Involved in the enollzation or the
ketone.
That i s ,
the enolate might be rormed by e ith e r
or the rollowing methods:
(CH^CORg) MgBr
+ R»H
RgCHCOCHg ♦ R’MgBr
(RgCHCOCHg)MgBr + R»H
(Rsneopentyl; R*» alkyl)
However, a l l the experimental evidence shows that the
t e r t ia r y hydrogen or dlneopentyloarbinyl group is extremely
d i m cult to remove, whereas, the hydrogens
or the methyl
and ethyl groups are very rea d ily removed.
When dineopentyl-
carblnyl phenyl, dlneopentyloarbinyl o -to ly l,
and dineo­
pen ty lcarb in y l p -to ly l ketones are placed in the Orlgnard
"machine" no enollzation occurs,
in these ketones the only
hydrogen available ro r enollzation i s the t e r t i a r y hydrogen
or the dineopentylcarbinyl group.
Furthermore, the methyl and eth y l ketones react with
bromine so vigorously th a t they must be cooled during the
re actio n .
The phenyl, o - to ly l, and p -to ly l ketones do not
re a c t with bromine a r te r ten hours heating at 80°.
5
One compound has been made In whlob th e te r t ia r y
hydrogen of the dlneopentyloarbinyl group la Involved In
enollxatlon.
The treatment of the bromomagnesium enolate
of dlneopentyloarbinyl ethyl ketone with dlneopentylaoetyl
chloride produoea 1 , 1-bis-(dlneopentylaoetyl)-ethane,
RgCHCOCH( CH3 ) COCHRg:
RgCHCOCHCH^MgBr ♦ RgCHCOCl m RgCHCOCH( CH3 ) COCHRg
(Rsneopentyl)
The 1 ,1-bls-(dineopentylaoetyl)-ethane can be methylated ( 6)
to produce 2 , 2-bls-(dlneopentylaoetyl)-propane,
RgCHCOC(CHj)gC0CHR2 (R'neopentyl)•
The only available
alpha-hydrogens In t h i s compound are those of the di neo­
pent ylearbinyl groups,
pound shows
in the Orignard machine th is com­
en olisatio n and 1 3 6 % addition (calculated
as moles of Orignard reagent per mole of dlketone).
The s te r lc e ffe c t of the dlneopentyloarbinyl group on
the carbonyl group Is fu rth er emphasised by an examination
of the properties of dineopentylcarblnylglyoxal, RCOCHO
(Rsdlneopentyloarblnyl) •
This compound can be prepared
from the bromomethyl ketone by the method of Relohsteln:
0HC#,H<
4H(CH3)o
jj-----RCOCHgBr+CgHgH • RCOCHgNCBr^sHg -------RCOCH H ( 0 ) C 6 H4 N (C H 3 > 2
„HC1
(Rcdlneopentyloarbinyl)
y
RCOCHO
(7)
6
The aldehyde carbonyl la rery reactiv e in th is compound.
I t read ily gives a p o sitiv e aldehyde t e s t with F ehllng's
and Tollens* solution and forms a 2,4-dinitrophenylhydrasone d eriv ativ e very e a s ily .
A f in a l Indication of the s te rlo effe o t of the dlneo­
pentyloarbinyl group can be observed In the reaction of
certain 1,3-dlketones with sodium hydroxide.
Ordinary
1 , 5 -dlketones are re ad ily cleaved with d ilu te
sodium
hydroxide ( 8 ) (9 ).
Compounds of the type (RCO^CHg,
(RC0)2 CHCH3 , and (RCO)gC(CH3 ) 2
(Rrdineopentylcarbinyl)
are t o t a l l y unaffected a f te r twenty-four hours of refluxlng
with 60£ a lk a li.
▼
H isto rica l
The In e rt carbonyl group of acetomesltylene has been a
subject of In te re s t for some years*
form an axlme (10)*
This compound does not
When heated with hydroyl amine for a
prolonged period at 160°, I t gives Instead acetylmesldlne
(11).
This Indicates a Beckman rearrangement of the oxlme,
which Is presumably formed very slowly(2 )s
(C H jJjC g H g C O C H j + MHgOH
CHjj JjC g H g C ^ C H j
(ch3 )3 c6h2 nhcoch3
£*»£>
—
Sodium hypobromite reac ts with ace tome s i tylene to g lre
a trlbromoketone Instead of the usual acid and bromoform(3) •
The ketone Is very r e s is ta n t to a lk a li
even a fte r a l l
(4) and remains so
the hydrogens of the methyl group are
replaoed by halogens (3 )*
Aeetomesitylene i s re a d ily reduoed to the secondary
alcohol with sodium and ethanol (4) and, according to
Klages rea cts with ethylmagnesium iodide to form an addi­
tio n complex, which can regenerate the ketone when tre a te d
with water*
He pictured th e formation of the addition
ooiqplex as follows ( 1 2 ):
OHs OO CgHjj ( C H j ) 3 +C 2 H5 M gI+ <C2 H6 ) 8 0 .
H<K ^
a
<cV s c 6H2/Nol<eC2H5- ^ a V a 0
8
Klages, however, fa ile d to notloo the evolution of goo
during the reao tlo n .
When Kohler made an active hydrogen
determination on aoetomesitylene in hie Orignard "maohlne",
he discovered th a t a q u an titativ e evolution of methane gas
occurred (13).
This Indicated th a t aoetomesitylene r e ­
acted as an enol.
The produot formed In addition to
methane was accordingly the broraomagnesium enolate of the
ketone:
(CH3 )3 C6H2 C0CH3 +CH3MgBr « HCH^jC^HgCOCHg ]MgBr
Other Investigators had previously reported the forma­
tio n of sim ilar enolates.
Umnova had reported the follow­
ing reaotlon:
BrC(CH3 ) 2 COCBr(CH3 )2+2C6H6MgBr = HC(CH3 )2 C0C(CH3 ) 2C6H3
The lntersiedlate compound In t h i s reaotlon i s unquestion­
ably the bromomagneslum enolate of the ketone.
Since the
Intermediate compound formed an acid when treated with
carbon dioxide and produced the ketone when tre a te d with
water, Umnova assigned to i t
the following stru cture:
C6 H5 C(CH3 )gOOC(CH3 ) 2 MgBr
Lowenbeln and Sohuster have reported the following reaotlon
(15):
CgH3 C0CBr (CgH3 ) £+2C3H3MgBr - CgHg-C^Hg+CgHgCOCHfCgHg^
Finally, Pus on, Fisher, and Oakwood have Investigated the
action of Orignard reagent on alpha-bromo-iso-butyrylmesitylene.
This reaction prooeeds as the two above
9
reactions
(16):
(CH5)3C6B5COCBr ( CH5 )2^R1(gX * (CHs )5 C6HeC0CH(CHs )2
Th« intermediate bromomagnesium enolate forms an acid when
treated with carbon dioxide and produces the ketone when
watsr is added,
Kohler and Batsley (2) have reported some reactions of
the bromomagne alum enolate of acetomesltylene •
The enolate
reacts with acid chlorides to form trlk eto n es
( CHg ^C gH gC O C H gM gB r+B C gH gC O C l s
(CH5 ) 3 C6 H 2C0C H (C0C6 H5 ) g .
They were unable to is o la te any 1,3-dlketones from these
reac tio n s.
When tre a te d with carbon dioxide, the enolate
formed a p re c ip ita te , but no acid was id e n tifie d .
The
enolate was unaffeoted when treated with a stream of oxygen.
The reactions of the bromomagneaium enolates of
several a e s lty l ketones have been thoroughly investigated
by Fuson and co-workers.
Enolates of the type RCOCHgA
(Rwmesltyl; A-H, halogen, or alkyl group) re a c t to give
products which would indicate th a t the enolate has the
structure of a Orignard reagent, RCOCHAWgBr.
They have
found th a t the enolates give 1,3-diketones with acid
chlorides, beta-keto acids with carbon dioxide, keto
secondary alcohols with benraldehyde, and keto t e r t i a r y
alcohols with benzophenone (17).
Oilman has found th a t the
bromomagnesium enolate of acetomesltylene gives a p o sitiv e
te s t for a Orignard reagent (18).
10
Kohler and co-workere have shown t h a t th e en o la tss or
m esltyl ketones (19) of th e typo RCOCHAg (Rwmesltyl; A*
halogen, a lk y l,
dlketones
or a r y l group) and the en o la te s of 1,3-
(20) of the type -COCHCOCgHg(CHg)g re a o t with
aold ch lo rid e s to produce O-aoylated p ro d u cts, enol e s te r s ,
in c o n tra s t to th e C -acylated products foriaed from the
en o lates of m esltyl ketones which do not possess a t e r t i a r y
hydrogen*
That O -aoylatlon I s a ffe o te d by th e m esltyl
group as well as by th e presence of a t e r t i a r y hydrogen Is
shown by th e f a c t t h a t 1,3-dlketones of the type -COCHCOCgHg
give almost e x c lu siv e ly C -acylatlon (19)•
The two types of
ae y latlo n of the en o la te s of m esltyl ketones have also been
rep o rted by Fuson and co-workers ( 2 1 )*
The e f f e c t of th e m esltyl group on the r e a c t i v i t y of
an adjacent carbonyl group has been re p o rte d In many other
compounds.
Dlmesltyl ketone
and dlm esltylg ly o xal
(2 ) a l l
(2 ), m esltylbensylglyoxal (22),
show I n e r t carbonyl groups*
The e f f e c t of th e m esltyl group Is e s p e c ia lly n o ticeab le In
the behaviour of m esltylglyoxal
(23).
Reactions Involving
the aldehyde group proceed q u ite r a p id ly , b u t the ketone
oarbonyl I s completely In e rt*
When re a c te d with o-phenyl-
enedlamine, a S o h lff base is produced Insteaui of the qulnoxa lln e u s u a lly formed by 1 , 2 -dlcarbonyl compounds (24)s
11
8 (CH ) 0 H .C O C H O ^ A - A » = CH°0CeHa<CH3)5
5 8
A
H2 « 'N ^ j
k ^ M -C H C O C a H g ( CHs ) 3
Fuson and co-workers have round th a t aea tome s i tylene i s not
cleaved by alk a lin e hypochlorite or hypobronite (3 ),
(85)
but in ste a d , th e tr ic h lo r o - or trlbromomethyl ketone i s
formed.
They have also found th a t a lk a lin e hypolodlte
produces the monoiodo- or dllodo-, b u t newer the t r i lodomethyl ketone (26).
The in a c tiv a tio n of the carbonyl group is often caused,
however, by adjacent groups other than m e slty l.
Smith and
Quss (27) have examined a number of aoe to and dlaoeto poly­
su b stitu te d phenyl ketones in a Orignard "machine."
They
have found th a t a l l d lo rth o su b stitu te d phenyl ketones show
100£ e n o llz a tio n .
They also rep o rt th a t s u b s titu tio n of
methyl groups on the para and ortho p o sitio n of the phenyl
group g re a tly increases the ex ten t of e n o llz a tio n .
Kohler
has found th a t the replacement of methyl hydrogens by
phenyl groups gives an Increase in e n o llz a tio n of the monoaoetophenone s e rie s
(13).
Puson has found th a t d io rth o -
su b stltu te d phenyl methyl ketones show the same reaotlons
with a lk a lin e hypohalite as in the ease of acetomesltylene.
In fa o t, he was able to achieve stepwise halogenstion with
such a compound (28).
All the In v estig a to rs seem to agree th a t the abnormal
reaotlons of a l l these ketones are due to s te r lo hindrance
12
of the m esltyl or other d io rth o su b stitu te d phenyl groups.
Many other In te r* s tin g observations and speculations have
also been made in regard to these compounds*
Orignard and Blanohon (29) suggest th a t e n o llsatio n
may be lnduoed by the nature of the Grignard reagent i t s e l f ,
since they claimed to have obtained en o llsatio n when cer­
ta in ketonea were reacted with iso-propylmagneslum bromide
and no e n o llsa tio n when the same compounds were reacted
with methylmagneslum iodide*
Kohler and Thompson, however,
proved t h a t the reputed e n o lls a tio n was in r e a l i t y reduc­
tio n and maintain that the nature of the Grignard reagent
has no e f f e c t on enollsation*
They maintain th a t i t
induced by the d i f f i c u l t y of ad d itio n .
addition i s a ttrib u te d to
is
The d i f f i c u l t y of
s te r lc hindrance ( 3 0 )*
Kohler has suggested th a t the re a c tio n between a
ketone and a Grignard reagent may, much more often than i s
generally supposed, involve a competition between en o llsa ­
tio n and normal addition
(13).
This idea i s
supported by
experiments which show th a t many ketones undergo both
reaotlons simultaneously (13)
(27).
Kohler also contends th at the mesltyl group tends to
s ta b i l i s e
the enol form of the ketone (18)
(19).
This con­
ten tio n finds considerable support from other investigators*
Luts and Wood found th a t the introduction of the m esltyl
13
group g r e a tly s t a b i l i z e s
the enol form,
<CH3 )5 C6 H2 COC(OH)*CHCOC6H2 (CH3 ) 3 (31).
rep o rte d a s ta b le en o l,
Barnes has also
(CgHg^C^C (OH)COCgHg (CH3 )3 , due to
the Influence of the m esltyl group (32)•
Green (33) have been able to I s o la te
Barnes and
the e n e -d io l,
CgH^C(OH)*C(OH)COCgHg(^^2 ^3 * Fuson and Coose (34) aid
Thompson (35) have I s o la te d 1 ,2 -d im eslty l acety len e glycol
(ch3 )3 c 6h2 c(o h )«c(o h)c 6h2 (ch3 )3 .
In attem pting to explain the r e a c tio n s o f the bromomagneslum e n o la te which Involve C -a cy latio n ,
e tc .,
Kohler s t a t e s
C-condensatlon,
th a t t h i s type of r e a c tio n may be pre­
ceded by k e to n lz a tio n o f the
enolate o r I t s
Ion
(18).
He
a ls o m aintains t h a t th e d iffe re n c e In mode of ac y latlo n of
m eslty l ketones containing
a t e r t i a r y hydrogen, O -acylation,
and those co n taining primary or secondary,
probably not due to d iffe re n c e in s t e r i c
Puson ex p lains
hindrance.
He b elie v e s t h a t
halogen In to the molecule I s
step In th e s e r ie s
is
the a lk a lin e halogenation of ketones In
terms of the enol form.
of the f i r s t
C -acy latlo n ,
(28).
Support fo r t h i s
the In tro d u ctio n
the c o n tro llin g
Idea I s o ffered
th e findings of Kohler and Sonnichsen on the p ro p e rtie s
of alpha-brom o-beta, b eta-d lp h en y lp ro p lo n y lm sslty len e.
This compound Is
extremely so lu b le In a lk a lin e
methanol,
while b eta,b eta-d ip h en y lp ro p io n y lm esity len e I s n o t.
Kohler
th e re fo re concludes th a t halogen s u b s tit u tio n enhances
14
e n o llzatio n .
Therefore a f te r the f i r s t halogen has been
introduced Into a ketone, the Inoreased, tendenoy toward
eno llzation should made subsequent halogenatlon qu ite
easy (36).
All the methyl ketones found in the l i t e r a t u r e which
shoe these strong evidences of s te r lc hindrance have a
d lo rth o su b stitu ted phenyl group adjacent to the carbonyl.
No e n tir e ly a lip h a tic methyl ketones,
showing suoh an in e r t
carbonyl have been found.
However, q u ite recen tly in th is
laboratory Randall has
found th a t c e rta in highly branched a lip h a tic ketones show
s te r ic e f f e c ts
lik e those shown by ketones containing a
mesltyl group (37).
16
Discussion
The behaviour of ketones containing the dineopenty1carbinyl group adjacent to the carbonyl shows c le a rly th a t
th is group has an e f f e c t on the a c tiv ity of the oarbonyl.
Only the methyl ketone gives a ketone derivative*
All
attempts to make oxlmes and 2,4-dlnltrophenylhydra8ones of
the other ketones studied were unsuccessful.
The e f f e c t of the dlneopentyloarbinyl group on an
adjacent carbonyl i s also shown in the reactio n of 1 , 3 diketones with a lk a li*
Benzolydineopentylacetylmethane and
1 -bensoyl-l-dlneopentylaoetylethane
are cleaved q u a n tita ­
tiv e ly in six hours with 50# a lk a li
to give exclusively
benzoic acid and the methyl and eth y l ketones resp ectiv ely :
RC0CH2 C 0C 6 H5
= RCOCHg ^CgHgCOQH
rcoch(ch 3 )coc6h6 z rcoc 2%*.c6h5cooh
(Rrdineopentylcarbinyl)
As already mentioned 1,3-dlketones of the type (RCOjgCHg*
(RCO)gCHCH3 , and (RCO)gC(CH3 ) 2 (R-dlneopentylcarblnyl) are
unaffected a f te r twenty-four hours of reflu xing w ith 60#
a lk a li.
To make an evaluation of the ex tent of the s te r lc
e ffe c t of the dlneopentylcarblnyl group as compared to th a t
of the mesltyl group i s q uite d i f f i c u l t , as the following
ta b le shows:
16
Reagent
1. 2,4-dinltrophenylhydraiIn©
Product
Dlneopentyloarbinyl Acetomesltylene
Methyl Ketone
2 ,4-dlnltrophenyl-
hydrasone
----
2. Hydroyl amine
No reaotlon
5. RmgX
Bromomagnealum
enolate
Br omomagnes lua
enolate
4* NaOH
No reaotlon
No reactio n
5. Na and ethanol
Carbinol
Carbinol
6 . Bromine
Monobromoketone
Monobromoket one
7. NaOBr
Dlbromoketone
Trlbromoketone
8 . HaOI
No reaction
Dllodoketone
The f i r s t two reaotlons indicate th a t the carbonyl of
acetonesitylene I s le ss re a c tiv e ,
or more s te r le a lly
hindered than th a t of the dlneopentyloarbinyl methyl ketone.
The next three reactions show no appreciable difference,
while the l a s t two would seem to indicate th a t the dineo­
penty lcarb in y l group has a g reater s te rlo e ffe c t than the
mesltyl.
Randall (37) has found th a t methyl-t-butylneopentylcarblnyl methyl ketone shows g reater s te r lc effe c ts than
e ith er of these oompounda.
This ketone cannot be hydro­
genated c a ta ly tle a lly , cannot be reduced with sodium and
ethanol or aluminum iao-propylate.
I t forms no derivatives
and reacts with Orignard reagents as the mesltyl and
17
dineopentyloarblnyl ketones do*
I t s fa ilu re to reduce is
in d icative of a very high degree of s te r ic hindrance.
Furthermore, the various ketones containing the din e open tyloarblnyl group show considerable difference in
th e ir behaviour toward methyl Grlgnard reagents.
The
following series is from determinations in a Grlgnard
"machine1
* by C. E. Lewis of th is laboratory:(46)
Ketone
% en o lisatlo n
% addition
DineopentylcarbinylMethyl
100
0
Ethyl
100
0
Phenyl
0
100
o-Tolyl
0
100
p-Tolyl
0
100
63
136
2 , 2 -bis-(dineopentyl-
a c e ty l)-propane
An examination of these data shows th a t the enolizatio n of dineopentylcarblnyl ketones cannot be a ttrib u te d
to s te r ic hindrance alone•
The carbonyl groups of the
phenyl, o -to ly l, and p -to ly l ketones are c e rta in ly as
s te r lc a lly hindered as those of the methyl and ethyl
ketones, while the carbonyls of the 1,3-dlketones shculd
be much more hindered than any other*
18
I t was thought th a t the addition of the methyl
Grlgnard reagent to the phenyl ketone might be a 1,4addltlon involving the benzene ring*
Such a reaction has
been reported by Kohler (38):
CgHgCH—
C(CgHg)COCgHg + CgHgKgBr
^ r a ( C 6H5 )-C |I
C6H6CH=C(C6H6)C0H«C
However,
x
the product proved to be the tertiary alcohol,
dlneope ntylcarblnylmethylphenylcarblnol,
OH
(Rcneopentyl)
r2chc- c6h6
CHS
In discussing the reaction of aoetomesltylene with
methylllthlum and phenyllithium, Gilman proposes the
following mechanism (18):
r
: C: CHo
R: C:: CH2
:0:H
» :5:
+ R*H
• •
• •
Id R*
Li
(R*mesityl; R**methyl or phenyl)
According to t h i s mechanism, there are two a lte rn a tiv e
reactions*
I f the usual course, addition, is made d i f f i ­
c u lt due to s te r ic hindrance,
the other p o s s ib ility , enoli-
zatlon, may be quantitative*
The a lte rn a tiv e reactio n ,
enollzation, is dependent on the presence of an alphahydrogen*
Furthermore, t h i s alpha-hydrogen must be removed
more rapidly than addition can occur*
19
By means of t h i s mechanism the reactions of the
various ketones v lth methyl magnesium bromide can be ex­
plained*
In the case of the methyl and ethyl ketones,
the
removal of the alpha-hydrogen occurs much more rapidly than
addition to the carbonyl group*
The Influence of the adja­
cent dlneopentylcarblnyl group causes the l a t t e r reaction
to be d i f f i c u l t .
Accordingly, a q u an titativ e enollsation
occurs.
When the methyl magnesium bromide i s added to the
phenyl, o - to ly l, and p -to ly l ketones,
the only available
alpha-hydrogen i s the te r tia r y hydrogen of the dlneopentyl­
carblnyl group.
All the experimental evidence indicates
th at th is hydrogen i s removed with extreme d if f ic u lty .
It
is not surprising, therefo re, to find th a t no enollsation
occurs.
Although addition may be d i f f i c u l t ,
the removal of
the t e r t ia r y hydrogen is even more d if f i c u l t and therefore
there is no evolution of methane gas.
In a l l of the ketones above there is evidently a great
difference in the d if f ic u lty of addition and the d if f ic u lty
of en o llsation , since the methyl and ethyl ketones show
q uan titativ e en ollsatio n and the phenyl, o -to ly , and pto ly l ketones show q u an titativ e addition.
In the case of
the 1,3-dlketone, 2 ,2 -b is- (dlneopentylacetyl)-propane,
however, th i s difference is g re a tly reduced.
In the r e ­
action of methylmagneslum bromide with th is compound, both
20
ad d itio n and e n o liz a tlo n oocur.
The two competing r e ­
actions are demonstrated q u ite d e a r l y in the case of th is
compound*
The d iffe re n c e in th e ease of removal of the alphahydro gens of the various ketones i s q u ite e a s ily detected
in other r e a c tio n s .
The bromination of the ketones as
previously mentioned, i s in complete agreement with th e
r e s u lts obtained In th e Grlgnard "machine"•
Certain highly branched Grlgnard reagents a re known to
give red u ctio n products*
The reduction of ketones I s
thought to be a slow process (39)*
to fin d , th e r e f o r e ,
It
i s not su rp risin g
th a t the methyl and e th y l ketones are
not reduced by these highly branched Grlgnard reagents*
The ease with which e n o liz a tlo n can occur prevents the
slower process, red u ctio n , from occurring*
The re a c tio n s of dineopentyloarblnyl ketones with
Grlgnard reagents Involves a competition between en o liza­
tlo n ,
ad d itio n and reduction*
The course which is
followed
depends not only on the s t e r i c e f f e c t of the adjacent d i ­
ne opentylcarbinyl group b u t also on th e ease of removal of
the a v a ila b le alpha-hydrogens*
On the b asis
of th is
explanation the ketones in v e s ti­
gated may be c l a s s i f i e d as follows:
21
C lass I*
The ease w ith which an alpha-hydrogen Is
removed excludes any r e a c t io n w ith OrIgnard re a g e n ts save
e n o llsa tio n *
There Is
no a d d itio n and,
h ig h ly branched Grlgnard re a g e n ts ,
no redu ction *
methyl and e th y l ketones belong to t h i s
Class II*
even w ith the most
The
class*
D espite s t e r i c h in d ran ce, a d d itio n takes
place more e a s il y than th e removal of a v ery t i g h t l y bound
alpha-hydrogen*
In t h i s
c la s s are the phenyl,
o -to ly l,
and p - t o l y l ketones*
Class I I I *
There i s
a d d itio n and e n o lls a tio n *
an observable com petition between
The 1 ,3 -d ik e to n e ,
(d ln eo p en ty la cety l)-p ro p an e I s In t h i s
class*
2 ,2 - b is -
28
Experim ental
I.
D e s c rip tio n o r Apparatus Used*
A.
Columns Used
A ll m a te r ia ls were f r a c ti o n a te d through, two columns*
Column I was a 65 x 1*5 cm* column e q u iv a le n t to 15
t h e o r e t i c a l p la te s *
able
II
ta k e o ff
was the
I t was th e
to ta l
condensation,
type packed with g la s s h e l i c e s
same type
(4 0 ).
v a ri­
Column
of oolumn b u t was 1*1 x 42 cm*
e q u iv a le n t to 10 t h e o r e t i c a l p la te s *
B* Z erevtlnov D eterm inations*
The a c tiv e hydrogen d e te rm in a tio n s were made In an
apparatus designed by Block (41)
Lewis of t h i s
II*
la b o r a to r y
and m odified by C* E*
(46)*
P re p a ra tio n o f S t a r t i n g M a te r ia ls .
A* P re p a ra tio n
of D ln e o p e n ty la c e tlc acid
(42)•
1* O xidation of D ineopentylethylene w ith Chromic Oxide
and A cetic Acid*
To a s o lu tio n
o f 134g (1*33 moles)
250cc of w ater was added 1 l i t e r
In a 3 neck 3 l i t e r
o f chromic oxide In
of g l a c i a l
a o e tlc acid*
f l a s k was p laced a m ixture of 1 l i t e r
of a c e tic a c id and 170g (1 M) of d in e o p e n ty le th y le n e , b*p*
oo
1745, n D 1.4380,reco vered from P fa u d le r k e t t l e o x id a tio n o f
23
I
trlsobutylene by Miner (1)*
a dropping funnel,
The flask was equipped with
a mercury seal s t i r r e r , and a therxnom-
eter •
The chromic oxide solution was dropped Into the flask
with stirrin g *
The temperature of the reaction was kept
below 30° during the addition.
After a l l the oxidising
agent was added the mixture was s tir r e d for twenty-four
hours*
At the end of th is time I t was poured Into a
separatory funnel and allowed to stand over night*
Two
layers separated*
The lower layer was run into an earthen crock, diluted
with 3 l i t e r s
hours*
of water and allowed to stand for twelve
The white cry sta ls th a t separated a t the surface
were removed with a spatula, f il te r e d with suction, washed
with water and dried between layers of f i l t e r paper.
To
these were added additional c r y s ta ls obtained by f i l t e r i n g
the e n tire contents of the crook and washing the c ry s ta ls
obtained.
The upper layer, which separated In the funnel, was
placed In a 2 l i t e r round bottom fla sk ,
200cc of 20% sodium
hydroxide solution added, and the mixture heated with s t i r ­
ring on the steam bath fo r one hour.
The mixture was cooled
and placed in a separatory funnel and the lower layer drawn
o ff.
On a c id ific a tio n with d ilu te su lfu ric acid, additional
*
24
cry stals of a d d wars obtained*
end fractionated*
I t s b oiling point,
1*4230, Id e n tifie d i t
A to ta l
The upper layer was dried
76° a t 35mm and n20D
as unoxldised dlneopentylethylene*
of 85g of dry acid, m.p* 88-9°, was obtained*
This represents 42*5^ oxidation*
A to ta l of 48g«, 2B.2%
of unaxldlzed o lefin was recovered*
2* Oxidation of dlneopentylethylene with Chromic Oxide and
Acetic Anhydride (43).
A solution of 66g (0*66 mole) of chromic oxide d is­
solved in 250cc of acetic anhydried was added with stirring
to a mixture of 35g (0*5 mole) of dlneopentylethylene and
450co of acetic anhydride.
as in above oxidation*
The apparatus used was the same
The addition required two hours
and the temperature rose to 45°.
The mixture was s tirre d
overnight*
A solid and liq u id phase were formed during the over
night stirrin g *
The liq u id was decanted into a d i s t i l l i n g
flask , and excess acetic anhydride d i s t i l l e d off, the
residue steam d i s t i l l e d , and the d i s t i l l a t e extracted with
ether*
The ether extract was shaken with lOOoc of 20^
a lk a li and the a lk a li layer removed in a separatory funnel*
The a lk a li layer on acidifying with d ilu te su lfu ric acid
yielded c ry s ta ls of acid*
The ether solution was saved*
25
The so lid phase was placed in 2 l i t e r s of water,
s tir r e d , and allowed to stand to dissolve the soluble
chromium s a l t s .
The Insoluble m aterial was f il te r e d by
suction, dissolved in 200oc of 20% a lk a li and separated
from the o ily layer th at formed.
The a lk a li la y e r on
acidifying yielded cry stals of acid.
The solution of chromium s a l t s was steam d i s t i l l e d ,
the d i s t i l l a t e
extracted with ether and the ether solution
combined with th a t obtained from treatment of the liqu id
phase.
The ether was removed on the steam bath.
An oily
residue was obtained.
The oily residue and the o ily layer obtained from the
a lk a li ex tra c tio n of the solid phase were combined and
d is tille d .
This m aterial,
22g, 25.9%, was id e n tifie d by
b.p. and index as unoxidized o le fin .
The to ta l yield of acid, m.p. 88-9°, a f te r drying was
61g, 61% y ie ld .
All other dineopentylacetlc acid used was
obtained by the oxidation of trliso b u ty len e in the Pfaudler
k e ttle as described by Miner (1).
B. Preparation of Dineopentylacetyl Chloride.
Large q u a n titie s of th is m aterial have been prepared.
A typical 1 mole preparation Including the fraotionatlon
of the a d d chloride i s given.
26
In a 500eo round bottom f la s k was plaosd 200g (1 mole)
of dlneopentylaeetlc acid, m.p. 98-9°.
The fla s k was
stoppered with a 1 hole stopper containing a re flu x con­
denser*
Through th is was added as ra p id ly as possible,
179g (1.5 moles) of Eastman*s fellow Label thlonyl chloride.
The e x i t o f the re flu x condenser was then connected to a
gas absorption tower and the mixture allowed to s i t fo r
twenty-four hours.
At the end of t h i s time the fla sk was
placed on a steam bath and refluxed fo r two hours.
I t was
then remowed and placed under Column 1 and the excess
thlonyl chloride remowed by d i s t i l l a t i o n .
The acid
chloride remaining was then d i s t i l l e d under reduced pres­
sure.
The following outs were taken:
Col.
Temp •
Head
Temp.
Weight
Total
Weight
1
106
102
8:1
1.4399
2Oran
10. 3g
10.3g
2
106
103
8:1
1.4428
20mm
10.4
20.7
3
106
103
8:1
1.4430
20mm
11.3
32.0
4
106
103
8:1
1.4430
20mm
12.4
44.4
6
106
103
•:1
1.4430
20mm
12.8
57.2
6
106
103
8:1
1.4432
20ima
13.5
70.7
7
106
103
8:1
1.4431
20mm
16.8
87.5
8
106
103
8:1
1.4429
20mm
17.1
104.6
9
106
103
8:1
1.4428
20mm
17.0
121.6
10
106
103
8:1
1.4430
20mm
16.9
138.5
Cut
Reflux
Ratio
Ref.
Index
P re ss•
27
Cut
Col.
Teiqp.
Head
Teiqp.
Reflux
R atio
11
106
103
8 :1
12
106
103
13
106
103
Ref.
Index
Total
Weight
P ress.
Weight
1 .4 4 3 1
20 n aa
1 8 .3
1 5 6 .8
8 :1
1 .4 4 3 0
20nm
1 8 .2
1 7 5 .0
8:1
1 .4 4 3 0
2 Omm
1 7 .4
1 9 2 .4
This re p re s e n ts a y ie ld of 8 7 .6£ of the th o o re tlo a l
q u an tity of d in eo p e n ty lacety l c h lo rid e .
C• P rep aratio n ofOrlgnard Reagents.
1. P reparation of Methyl magnesium Bromide.
Many p re p a ra tio n s of t h i s m aterial were made.
A
ty p ic a l p re p a ra tio n i s d escrib ed .
In a graduated 2 l i t e r round bottom f la s k were placed
48g (2 moles) o f
e th e r.
magnesium tu rn in g s and 800cc of anhydrous
The f la s k was stoppered with a two-hole stopper
f i t t e d with a tube fo r bubbling the methyl bromide in to the
eth er and a t r i d e n t b earing a re flu x condenser, dropping
funnel and a mercury s e a l s t i r r e r .
The o u tle t of the
system was connected with a Oilman tra p to p ro te c t the mix­
tu re from m oisture.
To the so lu tio n was added 2oc of
methyl iodide and then the methyl bromide was bubbled in ,
with s t i r r i n g ,
a t such a r a t e as to produce a steady re flu x .
The a d d itio n was continued u n t i l the magnesium was used up.
At the end of t h i s time the mixture was s t i r r e d fo r an ad­
d itio n a l hour.
u su a l.
A sample was then removed and t i t r a t e d as
The y ie ld was 84£.
28
2* Preparation of Ethylmagneslum Bromide.
In a graduated 2 l l t a r round bottom fla s k , equipped
with a tr i d e n t bearing a mercury aeal s t i r r e r , dropping
funnel and a re flu x condenser, were plaeed 24g (1.0m) of
magnesium tu rn in g s and 500oe of anhydrous e th e r.
Into th is
was dropped with s t i r r i n g 109g (1.0m) of Eastman White
Label eth y l bromide dissolved in a lOOoo of anhydrous
e th e r.
The system was proteoted from moisture with a o i l ­
man tr a p .
The addition required approximately one hour
and was accompanied by a steady r e f lu x .
When a l l
the
bromide was added, the mixture was s tir r e d for one hour.
A sample was removed and t i t r a t e d .
The y ie ld of such a
preparation was 92j6.
3. Preparation of iso-Propylmagnesium Bromide.
The preparation was id e n tic a l with the procedure used
for preparing ethylmagneslum bromide.
mined by t i t r a t i o n
The y ie ld as d e te r­
was 83$t.
4. Preparation o f iso-Butylmagnesium Bromide.
The procedure was c arrie d out as with the ethyl and
iso-propyl Qrlgnard reagents save th a t the rea ctio n was
s ta rte d with 2oo of methyl io d id e.
The y ield was 70%,
5. Preparation of t-Butylmagneslum Chloride.
In a graduated 1 l i t e r round bottom fla s k equipped as
in the p rep aratio n of e thy lmagne slum bromide wore plaeed
29
lOOcc of anhydrous othor and 24g (1.0 mole) of magnesium
turnings.
To t h i s was addsd 2 ec of methyl Iodide.
the e th e r began to r e f lu x ,
a
59°, n
rin g .
20
When
lOco of t-b u ty l chlo ride, b.p.
D 1.3855, was dropped Into the mixture with s t i r ­
The remainder of 93g (1.0 mole) of t-b u ty l chloride
dissolved In 250cc of anhydrous ether was then added with
s tir r i n g a t a ra te
required two hours.
to produee steady re f lu x .
The addition
At the snd of th i s time the mixture
was s tir r e d for an additional hour.
T itra tio n of a sample
showed a y ield of 70$.
6. Preparation of Fhenylmagneslum Bromide.
The preparation was id e n tic a l with th a t for ethy l­
magneslum bromide.
The y ield was 99$.
7. Preparation of p-Tolylmagnesium Bromide*
The proeedure was the same as th a t used to prepare
phenylmagnesium bromide.
The y ield was 90$.
The p-
bromotoluene used In th is preparation was made from Eastman
Yellow Label p -to lu ld ln e according to the d ire c tio n s in
Organic Syntheses (44).
S. Preparation of o-Toly lmagne slum Bromide.
The procedure fo r the preparation of th is m aterial was
lik e th a t for the preparation of phenylmagnesium bromide.
Yield was 92$.
The o-bromotoluene was prepared from East­
man Yellow Label o -to lu id in e according to the d ire c tio n s
given In Organic Syntheses (45)
I I I . Reactions
A. Addition of Dineopentylacetyl Chloride to
Methylmagneslum Bromide
A 2.4 molar solution of methylmagnesium bromide d is ­
solved In 5 l i t e r s of anhydrous eth er was prepared as In­
dicated above.
Through the dropping funnel was added with
s t i r r i n g 219g (1.0 M) of dineopentylacetyl chloride, b .p .
103° a t 20mm, n2°D 1.4430-3, dissolved In 20Occ of anhydrous
e th e r.
A very mild reflux occurred.
When the addition was
complete the mixture was heated with s t i r r i n g in a water
bath a t 50° for ten hours.
The mixture was then s tir r e d for
an additional twenty-four hours a t room temperature.
The
mixture was then decomposed by pouring into a mixture of ice
and ammonium hydroxide.
The water and ether layers were
separated in a separatory funnel, the water layer extracted
with three lOOoc portions of eth er,
the ether layers com­
bined, and dried over anhydrous potassium carbonate.
The
ether was then stripp ed off through a 25nsn indented column
on the steam bath.
c ry sta ls separated.
When the residue was cooled white
These c ry s ta ls were f i l t e r e d and re ­
c ry s ta lliz e d from eth y l acetate, m.p. 140-1°, mixed ra.p.
with dineopentylacetamide, prepared by bubbling dry ammonia
gas through dineopentylacetyl chloride,
140-1°.
The liq u id
51
was d l s t i l l s d
through Column I*
Its
Index and b oiling
point id e n tifie d i t as a unreaoted acid chloride.
A to ta l
of 168g of amide was obtained, 84.4JC and a to ta l of 28.3g,
13£ of acid chloride was recovered.
of the m aterial used.
products.
This accounted for 91%
There was no in dicatio n of any other
Under these conditions,
the a d d chloride and
methylmagneslum bromide did not r e a c t.
B. Addition of Methylmagneslum Bromide to
Dineopentylacetyl Chloride.
In a 3 l i t e r fla sk f i t t e d with a tr id e n t, bearing a
dropping funnel, reflux condenser and mercury seal s t i r r e r
was placed 219g (IP mole) of dineopentylacetyl chloride
dissolved in 300cc of e th e r.
a Oilman tra p .
The system was connected to
To t h i s was added 133oc, 0.2 mole as
determined by t i t r a t i o n ,
of methylmagneslum bromide d is ­
solved in anhydrous e th e r.
The mixture was heated with
s t i r r i n g and samples removed a t in te rv a ls and te ste d for
unreaoted Grlgnard reagent by the method of Oilman (5 ).
In th i s manner aliq u ot portions of Grlgnard reagent were
added in 0.2 molar q u a n titie s when a sample showed a
f a in t ly p o sitiv e Gilman t e s t ,
p o s itiv e .
844 hours.
since the te s ts were always
The time required for the t o t a l addition was
When the f i f t h to tenth additions were made,
larg s q u a n titie s of gas were evolved through the Gilsuua
tra p .
A sample of the gas was subjected to an O rsatt
32
analysis#
The gas gave negative t e s t s for carbon dioxide
and unsaturated gases.
A Dumas molecular weight determina­
tio n Indicated th a t the gas was methane.
The mixture was decomposed with w ater, the water and
ether layers separated, the water layer extracted with
lOOcc of eth er,
the ether layers combined and dried over
anhydrous potassium carbonate.
The dbher was stripped o ff
through a 25cm Indented column.
On cooling the residue a large quantity of c ry s ta ls
separated from so lu tio n .
This was f i l t e r e d o ff by suction
and r e c r y s ta llis e d from methyl alcohol.
Two solid products were obtained,
a white s o lid ,
m.p. 96-7° and a pale pink solid m.p. 157-8°.
gave strongly p o sitiv e
Both so lid s
enol te s ts with f e r r ic chloride.
The liq u id residu e which was f i l t e r e d from the
c ry s ta ls was then d i s t i l l e d through Column I a t reduced
pressure.
Cut
Col.
Temp.
The following cuts were taken:
Head
Temp.
Reflux
Ratio
Ref.
Index
Press.
Weight
Total
Weight
8.8g
1
87
92
10:1
1.4335
21mm
8.7g
2
105
104
10:1
1.4355
21mm
5.6
14.4
5
107
104
10:1
1.4355
21naa
2.8
17.2
4
107
104
10:1
1.4555
21mm
9.4
26.6
33
Col.
Temp*
Head
Ten$>.
Reflux
Ratio
5
107
104
10:1
1.4356
2loin
9.2
35.8
6
106
104
10:1
1.4357
2Inn
10.1
45.9
7
108
104
10:1
1*4359
21ns
11.3
57.2
8
108
104
10:1
1.4356
21mm
9.2
66.4
9
108
106
10:1
1.4360
2Inn
7.4
73.8
10
114
110
10:1
1.4420
21mm
8.3
82.1
11
120
110
10:1
1.4440
21mm
4.2
86.3
Cut
Ref.
Index
Press.
Weight
Total
Weight
A to ta l of 106g of material m.p* 96-7° was obtained In
a pure state*
was 14g.
The yield of p urified c ry sta ls, m.p. 137-8°,
Cuts 2 to 9 of the liq u id product, a to ta l of 65g
was taken as pure liquid product.
A sample, 3co, of Cut 5 was placed In 25cc of absolute
alcohol, saturated with 2,4-dinitrophenylhydrazine.
The
mixture was refluxed on the steam bath for five weeks.
It
was cooled and five drops of concentrated hydrochloric acid
added, and the mixture f ilte r e d .
Prom the p recip itate was
obtained by re c ry s ta lliz a tio n a derivativ e, m.p. 137-8°.
A Zerevltlnov determination was then made on a sample
of Cut 5 In a Grlgnard machine of the type described by
Kohler and Block (13) (40).
The volume of gas evolved cor­
responded to 100JJ enollsation. (46)
34
To a *01 M so lution or e thylmagnes ium bromide In lOOce
anhydrous other was added with s tir r in g 2g (0.01 )0 of a
sample of Cut S.
Hie addition was accompanied by the
▼igorous evolution of gas*
hour*
The mixture was s tir r e d for one
At the end of t h i s time a white p re c ip ita te was ob­
served in the reaction mixture*
Into th is with s t i r r i n g
was added 2*2g (0*01 M) of dineopentylacetyl chloride*
The
mixture was heated for one hour in a water bath and poured
into an Ice su lfu ric acid mixture.
The ether layer was
separated and dried over anhydrous potassium carbonate*
The ether was evaporated on a steam bath and the residue
ch ille d In an ic e - s a l t bath*
Hie so lid separating was
f i l t e r e d and re c ry s ta lllx e d from methyl alcohol*
The
needles obtained gave a p o sitiv e enol t e s t with f e r r i c
chloride*
A m.p. and a mixed m.p. with the white c ry s ta ls ,
obtained by adding methylmagneslum bromide to dineopentyl­
acetyl ch lo rid e, showed the two compounds to be id e n tic a l.
C* Preparation of Dlneopentylcarbinyl Methyl
Ketone, [ (CH^CCHg]gCH-C0-CH3 .
The preparation of the ketone was accomplished by
preparing a 2*4 molar solution of methylmagneslum bromide
and evaporating the eth er u n ti l the re su ltin g so lution was
a t le a s t 6 molar by t i t r a t i o n
per 166oc of solution)*
To th is was added 2l9g (1 M) of
dineopentylacetyl ch lo rid e.
under these conditions*
(1 mole of Orlgnard reagent
The reactio n was vigorous
The mixture was s tir r e d for one
35
hour a f t« r
the a d d itio n was complete*
i!he s o lu tio n v a t
than d ll u ta d w ith 1 11 tar* o f anhydrous o th e r and decomposed
by pouring onto an i c e - s u l f u r i c
ware se p a ra te d .
acid mixture*
The la y e rs
The e th e r la y e r and e th e r e x tr a c ts of the
w ater la y e r were then d rie d over anhydrous potassium c a r ­
bonate*
The e th e r was s trip p e d o f f in th e u su a l manner and
the resid u e f r a c tio n a te d
through Column X*
142*6g of th e ketone, b .p .
obtained*
In t h i s way
104° 21mm, n2°D 1*4355-60 was
This r e p r e s e n ts a 1 2 % yield*
In a d d itio n 32g
8*4£ of th e 1 ,5 -d lk e to n e , b is-(d in e o p e n ty la c e ty l)-m e th a n e ,
m*p* 96-7°,
was obtained*
D* R eactions of D lneopentylearblnyl Methyl Ketone
1* P re p aratio n o f D ln eo p en ty lcarb ln y lm eth y lcarb ln o l9
t <ch 5 > 3 CCH2 32 chohch 3 •
A 50g
sample
(0*25 M) o f the d ln e o p e n ty le a rb ln y l
methyl ketone washydrogenated by
Cook o f t h i s
laboratory*
A p re ssu re of 1500 lbs* of hydrogen fo r fo u r hours a t 200°
and 1500 lbs* f o r
two hours a t 200-52° was used*
c a t a l y s t was a c o p p er-sin e chromite complex.
absorbed a t o t a l o f 101 lbs*
f o r a 0*25 M sample I s
The aanple
The t h e o r e t i c a l ab so rp tio n
75 lbs*
a te d through Column I*
The
The m a te ria l was f r a c ti o n ­
The follow ing c u ts were ta k e n :
Col*
Head
Temp* Temp.
Reflux
R atio
1
105
lOO
6:1
1*4342
20mn
6*7
6*7
2
115
105
6:1
1*4381
20nm
3*1
9*8
Cut
Ref*
Index
Press*
Weight
Total
Weight
56
Col.
Temp.
Head
Tenp.
3
120
110
4
120
5
Reflux
Ratio
Ref.
Index
P ress.
6:1
1.4410
20mm
3.0
12.8
112
6:1
1.4419
20mm
3.6
16.4
120
113
6:1
1.4437
20mm
3.2
19.6
6
119
113
6:1
1.4445
20mm
2*6
22.2
7
119
113
6:1
1.4460
20mm
4.8
27.0
8
119
113
6:1
1.4467
20nu
4.7
31.7
9
118
113
6:1
1.4467
20mm
4.6
36.5
10
118
113
6:1
1.4468
20mm
4.6
41.1
11
118
113
6:1
1.4454
20mm
4.5
45.6
Cut
Weight
Total
Weight
A See sample of Cut 8 was placed In lOee of pyridine
To th i s was added 4g of 3,5-dlnltrobenmoyl chloride.
The
mixture was refluxed on the hot p la te fo r fo rty -eig h t hours.
A s o lid benzoate m.p. 97-8° was thus obtained.
I f Cuts 6
to 11 oan be considered as reasonably pure carblnol, t h i s
represents a 52% y ie ld .
2. Reduction of Dlneopentylearblnyl Methyl Ketone with
Sodium and Bthanol.
A mixture of 500eo of 95% ethanol and 25g (0.125 M)
of dlneopentylearblnyl methyl ketone
was plaeed In a 2
l i t e r fla s k equipped with a reflu x condenser.
Into th is
was added a t In terv als 50g (2.1 M) o f m etallic sodium out
Into small pleees.
37
When a l l the sodium was added, the mixture was re fluxed
on the steam bath for three hours*
The excess ethanol was
removed under reduced p ressu re, 200cc of water added and
the fla s k cooled*
The mixture was then a c id ifie d with 200ec of concen­
tra te d hydrochloric a d d and extracted with ether*
The
ether e x tra c t was washed several times with water and dried
over anhydrous potassium carbonate*
The dry solution was then placed under Column I ,
the
ether strip p ed off and the residue fractio n ated a t 20mm*
The following cuts were taken:
Col •
Temp,
Head
Temp*
1
111
104
2
111
3
Ref.
Index
Press*
8:1
1*4368
20mn
2*2
2*2
108
8:1
1*4405
20mm
4*0
6*2
116
116
8:1
1.4443
20mm
1.1
7.3
4
115
116
8:1
1.4448
20mm
1.8
9.1
5
115
116
8:1
1*4459
20mm
2*8
11.9
6
116
116
8:1
1.4459
20mm
3*3
15*2
7
116
116
8:1
1.4460
20mm
3*3
18*2
8
116
116
8:1
1.4461
20mm
1.9
21.1
9
116
117
8:1
1.4466
20mm
1.0
22.1
10
116
118
8:1
1.4481
20bsb
0.5
22*6
Cut
Reflux
Ratio
Weight
Total
Weight
38
Cuts 5 to 9,
13.5g, bA% y ield , represent the dineopen t yl-
carblnylmethylcarblnol.
A sample of Cut 7 gave s 3,5-
dlnltrobensoate, m.p. 97-8°, which showed no deprssslon
with the hsnsoats from the hydrogenation of dlneopentylearbinyl methyl ketone.
3. Reaction of Dlneopentylearblnyl Methyl Ketone with
Aluminum iso-P ropylate.
A mixture of 25g (0.125 M) of dlneopentylearblnyl
methyl ketone, 13g (0.063 M
) of aluminum Iso-propylate, and
18g (0.32 M) anhydrous lsopropyl alcohol were placed In a
lOOcc round bottom fla s k .
The fla s k was plaeed under
Column I I and heated to b o ilin g fo r tw enty-fire hours.
There was no re flu x a t the top of the column.
The lsopropyl alcohol was then d i s t i l l e d off and the
residue poured Into w ater.
The water solution was ex­
tra c te d three times with ether and the ether ex tract washed
seven times with water and dried over anhydrous potassium
carbonate.
The eth er was removed on the steam bath and the r e s i ­
due d i s t i l l e d
through Column I I .
A recovery of 22g QQ% of
o
unreacted dlneopentylearblnyl methyl ketone, b .p . 104 at
20
2lima, n*wD 1.4355-61 was obtained.
The reactio n waa repeated using the same molar quan­
titie s
of m ate rials.
The mixture was placed under ColumnII
39
and boiled fo r alght days with the coluan sa t for to t a l
take-off*
During th i s time a small amount of d i s t i l l a t e
with the odor of aoatone was obtained.
The reactio n mixture was then tre a te d in the same
manner as before and the dry ether solution was placed
under Coluan I I .
The ether was stripped off and the r e s i ­
due fractio n ated a t 40asn.
The following cuts were taken:
Col.
Temp*
Head
Temp.
1
120
118
8:1
1*4366
2*1
2.1
2
120
118
8:1
1.4379
2*5
4*6
3
120
118
8:1
1*4395
0.8
5.4
4
120
120
8:1
1*4423
0*8
6.2
5
120
124
8:1
1*4455
0.8
7.0
6
123
127
8:1
1.4457
1.1
8.1
7
123
127
8:1
1.4456
2*2
10.3
8
123
127
8:1
1*4460
3.5
13.8
9
123
127
8:1
1*4461
4.1
17.9
10
123
127
8:1
1.4459
4.1
22*0
11
123
128
8:1
1*4464
0.9
22.9
Cut
Reflux
Ratio
Ref.
Index
Weight
Total
Weight
Cuts 5 to 10, 15.8g, 63# y ield represents the carblnol*
sample of Cut 8 gave a 3,5-dinitrobenzoate, m.p. 97-8°,
which gave no depression with the benzoates previously
prepared*
A
40
4* The Reaction of Dlneopentylearblnyl Methyl Ketone with
Grlgnard Reagents.
a. Reaction of Dlneopentylearblnyl Methyl Ketone
with 1ao-Propy lmagne slum Bromide.
To a 0.2 Mso lu tio n of lso-propylmagneslum bromide In
a 500oc fla s k with dropping funnel, mercury seal s t i r r e r ,
and reflux condenser was added with s tir r in g 20g (0.1 M) of
dlneopentylearblnyl methyl ketone.
The o u tle t tube from
the condenser was connected to a dry lee trap and a d ilu te
solution of potassium permanganate.
During the addition a vigorous evolution of gas
occurred.
The potassium permanganate solution was not
decolorized.
After a l l the ketone was added,
the mixture
was s tir r e d for one hour, then poured onto ic e -s u lfu ric
acid mixture.
The ether layer was separated, the water
layer extracted with 50cc of ether,
the ether layers com­
bined and dried over anhydrous potassium carbonate.
The
dried solution was then placed under Column I I , the ether
removed a t atmosphere pressure, and the residue d i s t i l l e d
a t 22xtm pressure.
The following cuts were taken:
Reflux
Ratio
Ref.
Index
Total
Weight
Cut
Col.
Temp.
Head
Tenp •
1
106
104
8:1
1.4355
1.8
1.8
2
106
106
8:1
1.4356
1.9
3.7
3
106
105
8:1
1.4358
1.8
5.5
4
106
105
8:1
1.4358
1.7
7.2
Weight
41
Cut
Col*
Temp*
Head
Temp*
5
106
105
8:1
1*4558
1.9
9*1
6
107
105
8:1
1*4558
2*1
11.2
7
107
106
8:1
1*4558
1.6
12.6
8
107
106
8:1
1*4559
1.6
14.4
9
107
107
8:1
1*4560
1.9
16.5
10
107
107
8:1
1*4561
1.0'
17.5
Reflux
Ratio
Ref*
Index
Weight
Total
Weight
This represents by b .p . and index an 86.5# recovery of the
dlneopentylearblnyl methyl ketone*
b. Reaction of Dlneopentylearblnyl Methyl Ketone
with 1a o-Butylmagne alum Bromide.
Proceeding In the same fashion as above and with the
same set up 20g (0.1 M) of dlneopentylearblnyl methyl
ketone were added to a 0.2 M solution of iso-butylmagneslum
bromide.
The addition was accompanied by a rapid evolution
of gas* which did not decolorise the potassium permanganate
solution*
When the addition was conflated,
the solution was
s tir r e d fo r one hour and then poured onto an lo e-su lfu rlc
acid mixture*
The ether layer was separated* the water
layer extracted with ether and the e x tra c ts added to the
o rig in al ether layer* and the whole ether solution dried
over anhydrous potassium carbonate.
The ether was then
stripped off through Column I I and the o ily residue fra c ­
tionated a t 21mm*
The following outs were taken:
42
Cut
Col*
Temp*
Head
Temp*
1
103
104
8 il
1*4354
1.5
1.6
2
103
104
8:1
1*4357
1.4
2.9
3
103
104
8:1
1*4358
1.6
4*5
4
103
104
8:1
1.4357
1.7
6*2
5
103
104
8:1
1*4358
1.7
7.9
6
103
104
8:1
1.4360
1.4
9.3
7
103
105
8:1
1.4360
1.4
10.7
a
103
105
8:1
1.4360
1.2
11*9
9
104
105
8:1
1*4360
1.6
13.5
10
105
105
8:1
1*4359
1.8
15*3
11
105
106
8:1
1*4360
1.6
16*9
Reflux
Ratio
Ref*
Index
Weight
Total
weight
This rep resen ts, by index and b .p ., an 84.5£ recovery of
dineopentylcarblnyl methyl ketone*
o. Reaction or Dineopentylcarbinyl Methyl Ketone
with t-Butylmagneslum Chloride.
To a 0.2 M solution of t-butylmagneslum chloride,
prepared in the usual manner,
was added 20g (0.1 M) of
dineopentylcarbinyl methyl ketone.
the same as above.
The apparatus used was
During the addition there was a vigor*
ous evolution of gas.
The potassium permanganate solution
was not decolorised*
After the addition was complete, the mixture was
poured onto an lee-sulfuric acid and worked up in the usual
manner*
The re su ltin g ether solution was thsn plaoed under
Column I I , the ether stripped o ff, sad the residu al o il
fractio n ated a t 21mm pressure*
The following cuts were
taken:
Cut
Col.
Tea*.
Head
Temp,
1
103
103
9:1
1*4352
1*6
1.6
*
104
104
9:1
1*4365
1.7
3.3
3
104
104
9:1
1.4369
1.7
5.0
4
103
104
9:1
1.4358
1.3
6.3
5
105
104
9:1
1*4360
1.6
7.9
6
105
104
9:1
1*4357
1*5
9.4
7
105
106
9:1
1.4360
1*3
10.7
8
105
105
9:1
1.4360
1.4
12.1
9
106
106
9:1
1.4361
1.5
13.6
10
106
106
9:1
1.4360
1.6
15.2
11
106
106
9:1
1*4560
1.1
16.3
12
106
106
9:1
1*4361
1.0
17.3
Reflux
Ratio
Ref*
Index
Weight
Total
Weight
residue of 1 •lg which would not d i s t i l l a t 191° at a
pressure of 21ns was l e f t In the p o t.
The amount of
recovered ketone was 17.8g, 89£.
5* Reaction of Dlneopentyloarblnyl Methyl Ketone with
Sodi u m Hypobromite:
Preparation of the Dibroaioketone,
[ ( CHj)jCCHg]gCHCOCHBrg•
In a 500co three neok fla s k , with mercury seal stirrer,
reflu x condenser, and dropping funnel, was placed 200co of
44
an lea water solution or 16g (0.4 M) of sodium hydroxide.
The fla sk was ismmrsed In an loa s a lt bath and s tirre d for
th ir ty minutes.
At the and of th i s time 32g (0.2 M) of
Dow*s bromine was added dropwise with s t i r r i n g .
After the
addition of the bromine was completed, the mixture was
s tir r e d for one hour.
To th is was added with s tir r i n g
20g (0.1 M) of dineopentylcarbinyl methyl ketone.
The
mixture was then s tir r e d for fo rty -e ig h t hours and allowed
to come to room temperature*
The mixture was then steam d i s t i l l e d u n til no more o il
passed over In the d i s t i l l a t e .
Hie d i s t i l l a t e was extracted
with e th e r, the ether solution dried over anhydrous potas­
sium carbonate, and the ether stripped off through a 25cm
Indented column.
The residue was unreacted ketone.
bromoform was found.
No
Left in the flask during the steam
d i s t i l l a t i o n was a white s o lid .
This was f il te r e d off and
r e c ry s ta llis e d from methyl alcohol showing a m.p. 62-63°.
The f i l t r a t e
was a c id ifie d with d ilu te sulfu ric acid
and the bromine vapors removed in the hood by blowing a
stream of a ir over the surface of the mixture.
The solid
separating was f i l t e r e d and re c ry s ta llis e d from methyl
alcohol.
There was no dlneopentylaoetic acid found.
The
solid showed a m.p. 62-3°, no depression with the so lid
obtained above.
Calculated for bromine: 44.9; Found: 44.6.
Mol. Wt. Calculated: 356; Pound (in bensene) 353.
45
6. Preparation of the Monobromoketone, £ (CH^J^CCHg J^CBCOCiyEk*.
In a 1 11t a r ,
three neok fla s k vara plaoed 150g of
dlneopentylcarblnol methyl ketone.
The flask was equipped
with a mercury seal s t i r r a r In one neck and a re flu x con­
denser in another neok.
The th ir d naok supported a drop­
ping funnel end in le t tuba.
The dropping funnel was
charged with 160g (0.57 M) of Dow's bromine.
was added with vigorous s t i r r i n g .
The bromine
The reaction was very
rapid and the hydrogen bromide lib e ra te d was removed by a
stream of dry carbon dioxide bubbled through f o r an addi­
tio n a l hour.
The mixture was then placed in a separatory funnel and
washed with three portions of water, three portions of
d ilu te potassium carbonate solution, and again with three
portions of water.
The pale yellow o i l was then dried over
anhydrous potassium carbonate.
The o il was then c h ilie d in an ic e - s a lt bath and the
c ry sta ls separating were f il te r e d o ff.
This process was
repeated u n t i l c h illin g produced no fu rth er o ry s ta ls .
The
solid obtained was re o ry s ta llis e d from methyl alcohol,
m.p. 33-4°•
A to ta l of 103g of so lid was obtained.
The re sid u al o il was d i s t i l l e d through a Clalsen flask
a t 20nsn and separated into the following fra c tio n s:
46
1. Bolling below 170°
-- 33g
2. Bolling below 170-180° — 24g
5. Bolling below 180-1909 - - 21g
Each of the three cuts wee ohilied in an le e - s a l t
bath*
Fran Fraction 1, 17g; from Traction 2,20g;
from Fraction 3,
19g of s o lid , m.p.
and
33-4°, wereobtained.
This represents a 76.2 yield of pure product.
Calculated: 277; Found (in bensene) 281.
Mol. Wt.
Br. Calculated:
28.88^; Found: 28.37£.
7. Reactions of the Monobromoketone.
a. Reaction of Monobromoketone with Zinc and Acetic
Acid.
In 2&oc of g la c ia l aoetlo sold In a 50cc Bhrlenmeyer
fla sk were plaoed 2.77g (0.01 M) of the bromoketone, m.p.
32-3°, obtained by d ir e c t bromlnatlon of dineopentyl­
carbinyl methyl ketone and 2.6g (0.04 M
) of sine dust.
The mixture was plaoed on a hot p la te and refluxed for
twelve hours.
At the end of th is time the solution was decanted
from the so lid m aterial and d ilu ted with lOOcc of water.
I t was then extraoted with 50oc of ether and the ether
washed with d ilu te potassium carbonate solution u n ti l a l l
the acetic acid was removed.
The ether solution was then
dried over anhydrous potassium carbonate.
47
The ether was removed under reduced pressure and the
on
re su ltin g o i l showed n D 1.4358 and negative halogen t e s t .
Yield of o i l ,
16g, 80*.
The s o lid residue was Shaken with water and the excess
sine removed by f i l t r a t i o n .
The water solution gave a
p o sitiv e halogen t e s t .
b. Reaction of Monobromoketone with Pyridine.
A mixture of 2.77g (0.01 M
) of the broaoketone and
16g (0.2 M) of dry pyridine was placed in a lOOcc Khrlenmeyer flask and refluxed fo r twelve hours.
action a s o lid separated out.
During the r e ­
The liq u id material was de­
canted and the solid re e ry s ta llls e d from bensene, m.p.
214-5°.
The y ield was 2.6g, 91*, which Is more than the
th e o re tic a l yield of pyridine hydrobromide which could be
formed by dehydrohalogenation.
i
The m aterial was soluble in water, and d ilu te hydro­
chloric acid.
When tre a te d with d ilu te sodium hydroxide, a
bright yellow p re c ip ita te was formed.
could be detected.
Mo odor of pyridine
This is the pyridlnlum s a l t ,
( (CH^CCH^gCHCOCHg-MCgHg
Br
c. Reaction of Monobromoketone with Alcoholic
Potassium Hydroxide.
A mixture of 2.77g (0.01 M
) of the bromoketone, 2g of
potassium hydroxide (0.04 M) and 25cc of absolute alcohol
48
were plaoed In * 100cc Bhrlenmeyer fla sk and refluxed on
the steam bath for twenty-four hours.
The solution was do-
canted fro* the so lid which separated, d ilu te d with lOOoc
of water and then extracted with 25ce of eth er.
The ether
extraot was washed with water to remove the alcohol, dried
over anhydrous potassium oarbonate and the ether evaporated
on the steam b a th .
In t h i s way was obtained 1.8g of o i l .
A mixture of 0.9g of the above o il , 0.5g of ehromlo
oxide and 50oc of g la c ia l aoetlo acid was allowed to stand
for twenty*four hours a t room temperature.
The mixture was
d ilu te d with lOOcc of water and extracted with eth er.
The
ether was washed repeatedly with water u n til a l l the
chromic oxide and aoetlo aold were removed.
shaken with 25cc of 10^ a l k a l i .
I t was then
The a lk a li layer was re­
moved, heated on the steam bath fo r five minutes, and
a c id ifie d with d ilu te su lfu ric acid.
The solid separating
was f i l t e r e d and c r y s ta llis e d from methanol, m.p. 88-9°,
no depression when mixed with a saaple of dine opentylaoe ti c
acid.
A mixture of another 0.9g of o i l , 0.5g of Eastman
White Label acetyl chloride, and lOcc of dry pyridine was
refluxed on a hot p late fo r twenty-four hours.
The solution
was d ilu te d with 25oc of water and extracted with e th e r.
The mixture was washed with d ilu te hydrochloric aold, water,
d ilu te potassium carbonate solution, and water successively.
49
The ether solution was dried over anhydrous potassium
earbonate, the other removed on the steam b ath, and the
residue c ry s ta llis e d from methyl alcohol, yield 0.4g,
o
m.p. 40-1 .
d. Reaction of Monobromoketone with Potassium
Acetate-Acetic Acid.
A mixture of 3g (0*04 M) of fused potassium acetate,
2.77g (0*01 M) of the bromoketone, and 20oc of g la c ia l
acetic a d d was refluxed on a hot p la te for twelve hours.
The mixture was f il te r e d , diluted with 50cc of water, and
extracted with e th e r.
The ether solution was washed with
water, dried over anhydrous sodium sulphate, and the ether
removed on th e steam b ath.
The residue was c ry sta lliz e d
from methyl alcohol, y ield 0.2g, m.p. 40-1°, no depression
when mixed with the product from the reaction of the
hydroxy compound with acetyl chloride.
The combined acetoxy compound obtained was heated with
lOco of \0% alcoholic potassium hydroxide for twenty-four
hours on the steam bath.
The mixture was d ilu te d with
15oc of water and extracted with eth er.
The ether solution
was washed with water, dried over anhydrous potassium
carbonate, and the ether removed on the steam bath.
When
the o ily residue was oxidized with chromic oxide, dlneopentylacetlo acid, m.p. 88-9°, was obtained.
50
8* The Reaction of Dineopentylcarbinyl Methyl Ketone
with Sodium Hydroxide*
A mixture of 25g (0.125 M) of dineopentylcarbinyl
methyl Icetone and 50oo of
sodium hydroxide solution In
a 250oc Bhrlenmeysr flask was plaoed on a hot plate and
refluxed for ten days.
*Bie mixture was cooled, neutralized
with d ilu te su lfu ric acid and extracted with e th e r.
The
ether solution was washed with water and dried over anhy­
drous sodium s u lfa te .
The ether was removed on the steam
bath and the residue fractionated through Column I I a t
20m«
The following cuts were taken:
Cut
Col.
Temp •
Head
Temp.
Ref. Index
1
IOO
102
1.4349
2-10
101
105
1.4354-60
Weight
Total
Weight
1.2
1.2
21.7
22.9
Residue l . l g
On a basis of Index and boiling po int, the ketone Is un­
affected .
Recovery 86.8^6.
The above process was repeated using 10#, 20#, and 25#
solutions of sodium hydroxide.
reaction In any ease.
lhere was no Indication of
The recovery was 85-90# In each case.
9. Attempted Alkylatlon of Dineopentylcarbinyl Methyl Ketone.
In a 500cc flask was placed 25g (0.125 M
) of dineo­
pentylcarbinyl methyl ketone.
To th is was added 2»5g
(0.125 M) of sodium shavings.
The addition was accomp&iriad
51
by the slow evolution of gas.
tbs sodium disappeared.
methyl iodide.
The mixture was heated u n til
To th is was added 25g (0.15 M) of
The mixture was connected to s u lfu ric acid
trap and refluxed for f ir e hours.
the mixture was then d iluted with lOOeo of water and
extracted with e th e r.
The ether solution was dried over
anhydrous potassium carbonate.
The dried ether solution
was placed under Column I I , the ether stripped o ff and the
residue fractio n ated a t 20mm.
The following cuts were
Cut
Col.
Teaq?.
1
lOO
96
8:1
1.4351
3.2
3.2
2
102
lOO
8:1
1.4358
2.8
6.0
3
105
lOO
8:1
1.4357
2.9
8.9
4
105
103
8:1
1.4358
3.0
11.9
5
106
103
8:1
1.4356
2.9
H
6
106
103
8:1
1.4357
2.7
17.5
7
106
104
8:1
1.4358
2.7
to
O
•
to
takens
8
106
105
8:1
1.4358
3.0
23.2
Head Reflux
Tenp • Ratio
Ref.
Index
Weight
Total
Weight
00
4
*
The b o ilin g point and index Indicate th at no alkylatlon
occurred.
10. Attempted Oxidation of Dineopentylcarbinyl Methyl Ketone.
A mixture of lOg (0.5 M) of dineopentylcarbinyl methyl
ketone, lOg (0.1 M) of chromic oxide, and lOOoc of 90%
52
a c e tic acid was plaoad in a 260oo Shrlenmeyer fla sk and
heated a t 60° for twenty-four hour*.
The mixture was
cooled, diluted with 100cc of water and extracted with
50cc of ether*
The ether extract was washed with water
several tin es to remove the chromic oxide and acetic acid*
I t was then washed with 2&oc of 1.0% sodium hydroxide*
The
sodium hydroxide layer was aoid ified with d ilu te su lfu ric
add*
No c ry s ta ls separated*
The acid ified waterlayer was then extracted with ether
and the ether removed on the steam bath*
heated under reduced pressure u n til
was dry*
The residue was
the containing flask
There was no evidence of any dlneopentylaoetle
acid*
The o rig ln al eth er extract was dried and the ether re ­
moved through Column I I .
The residue was fractio nated .
«
20
to t a l of 7.3g of m aterial, b.p* 104-6° at 20mm, n
1.4349-61 was obtained.
A
D
This represents a 1Z% recovery of
ketone•
11* Reaction of Dineopentylcarbinyl Methyl Ketone with
Sodium Hypolodite*
The procedure of Puson (26) was used three d iffe re n t
times in an e f f o r t to prepare an lododerlvative.
There was
no indication that an lododerlvative was formed at any time.
The treatment gave only unreacted ketone*
69
The procedure used wee as follows:
To a solution of
lg of methyl ketone In a mixture of 50cc of dloxane and
lOeo of 10* sodium hydroxide was added with shaking, 4g of
Iodine*
The solution was shaken fo r an additional fifte e n
minutes u n t i l a l l the Iodine oolor disappeared*
The solu*
tlon was then diluted with 50ee of water and extracted with
bensene*
pressure*
The bensene solution was removed under reduced
The o ily residue contained no c ry s ta ls , and gave
a negative halogen t e s t when a sodium fusion was done*
8. The Reactions of the Bromomagneslum Enolate
of Dineopentylcarbinyl Methyl Ketone*
1* The Oilman Or1guard Test*
To a 0*05 M solution of ethylmagneslum bromide In
lOOce of anhydrous ether was added with s tir r i n g 20g (0*111)
of dineopentylcarbinyl methyl ketone*
The mixture was
heated a t reflux for fiv e days, while protected from mois­
ture with a su lfu ric acid trap*
At the end of t h i s time
the mixture was cooled and a 0*5oc sample removed and sub­
jected to the Oilman t e s t for a Orlgnard reagent*
The
sample gave a very strongly positiv e test*
2* The Preparation o f Acetyldlneopentylacetylmethane,
CI^COCHgCOCHl CHgC(
)s ]g .
Into a 0.1 Msolution of ethylmagneslum bromide in
lOOcc of anhydrous ether was added with s tir r i n g 20g (O.IM)
of dineopentylcarbinyl methyl ketone*
The addition was
54
accompanied by a rapid evolution of gas*
After tha addi­
tion was complete, the mixture was a tlr r a d for one hour,
a t which time the bromomagneslum enolate separated as a
white e ry s ta llln e mass.
To th is mixture was added with
s tir r i n g 7.0g (0.1 M) of Eastman White Label acetyl
chlo ride.
The mixture was s tir r e d for two hours a f te r the
addition was complete and then poured onto an ic e -s u lfu ric
acid stixture.
The ether layer and ether ex tra c ts of the
water layer were combined and dried over anhydrous potas­
sium carbonate*
The ether was stripped o ff on the steam
bath and the residue d i s t i l l e d from a Clalsen fla sk at 5mm
pressure* The portion b o ilin g 134-7° gave a po sitive enol
te s t with f e r r ic chloride and formed a 2,4-dinitrophenyl
hydrazone immediately on shaking with the reagent*
The
d eriv ative melted 134-5°*
3* The Preparation of Benzoyldlneopentylaoetylmethane,
CeHgCOCHgCOCHL ch2 c (
)3 ] .
The same procedure and molar q u a n titie s as above were
used.
The re su ltin g product, a so lid , m.p* 73-4°, gave a
p o sitiv e enol te s t and a 2,4-dinitrophenylhydrazone deriva­
tive melting 177-8°.
Yield 12.3g, 40 .7£.
Mol. Wt. Calcd.
302; Found (In benzen£ 299.
A lOg sample of the m aterial was placed In a 50oc
flask and 25oc of 60# sodium hydroxide solution added.
mixture was refluxed on a hot p la te for six hours.
The
The
55
mixture mas then cooled end extracted with e th e r.
The
water solution was heated to remowe the ether and a c id ifie d
with d ilu te eu lfu rio acid .
The crystal*which formed were
f i l t e r e d and re cry a t a i n t e d from hot water, m.p. 121-2°,
without depression when mixed with an authentic saiqple of
benzoic acid.
Yield 3*9g, 94#.
The ether layer was washed with water and dried over
anhydrous potassium carbonate*
The ether was removed under
Column I I and the residue fractio n ated a t 20mn.
3.1g of m aterial, b .p .
A t o t a l of
104-6°, n20D 1.4350-60 was obtained*
This represents a S2% y ie ld of dineopentylcarbinyl nmthyl
ketone*
4. Preparation of M ethyl-t-butylneopentylacetyldineopentylacetylmethane,
C(CH,)I
v
3
( CHg)3CCH2C(CH3 )COCHgCOCHl CHgC(
>3 ]
A 0.05 M solution of the bromomagneslum enolate of d i­
neopentylcarbinyl methyl ketone was prepared in the usual
way.
To th is was added with s tir r i n g ll g
(0.05 M) of
m ethyl-t-butylneopentylacetyl chloride, prepared by Randall
of th is laboratory.
The mixture was heated for fcur hours
and decomposed In the usual fashion.
From the dried ether
layer was obtained, a f t e r strip p in g off the eth er, whits
c ry s ta ls , m*p. 89-90°,
Yield 9.3g, 49$£.
376, 384.
showing a positiv e enol test*
Mol. Wt.: Calcd. 380; Pound (in benzene)
56
A 0*05 M solution of the brononagnesluiD enolate of
methyl-t-butylneopen tylcarbinyl methyl ketone, prepared by
Randall o f t h i s laboratory, was then treated with l l g
(0.05 M) or dlneopentylacetyl chloride.
This reactio n
yielded on tre a tin g as above, c r y s ta ls , m.p. 89-90°, giving
a p o sitiv e enol t e s t .
A mixed melting point with the
m aterial obtained above showed no depression.
5. Preparation of Phenyl-(beta-keto—
gamma,gamma-dineopentylpropyl)-carbinol, C6H5CHOHCHgCOCH[CHgC(CH3 )s ]g.
To a 0.05 Msolution or the bromomagneslum enolate or
dineopentylcarbinyl methyl ketone In SOcc or anhydrous
ether was added with s t i r r i n g 5.5g (0.05 M) or rresh ly
d i s t i l l e d Eastman White Label bensaldehyde•
The mixture
was heated at reriux ror three hours and then poured onto
an lce-B u lfu ric acid mixture.
I t was then treated In the
usual fashion and when the ether was removed the residue
s o lid if ie d . The crude material was re c ry sta lU se d from
methanol to a constant melting p o in t,
89-90°.
Yield 8.5g,
54.9*.
A 5g sample of th is m aterial was mixed at room tempera­
ture with 5g of chromic oxide in 50cc of 90* a c e tic acid.
At the end of three hours there was no indication of oxida­
tio n .
hours.
The mixture was then heated a t 60° for twenty-four
On working up In the usual manner, 3.3g of material,
melting a t 73—
4° were obtained.
A sanple of th is m aterial
57
gave no depression In melting point vhen mixed with a
sample of benzoyldlneopentylacetyi methane previously
prepared.
Preparation of Diphenyl-(beta-keto-gamma,gamma-dineopentylpropyl) - oarbinol, (CgHg)gC0HCH2C0CH[CHgC(CH3 )g]g.
To a 0.05 M so lu tio n of the bromomagneslum enolate of
dlneopentylearblnyl methyl ketone In 50oe of eth er was
added with s t i r r i n g lOg (0.05 M) of Eastman White Label
benzophenone dissolved In 25oc of anhydrous e th e r.
The
mixture was refluxed fo r twenty-four hours and then worked
up In the usual manner.
The ether was removed under re ­
duced pressure and th e residue s o lid ifie d .
The crude
m aterial was re o ry s ta lllz e d from methanol to a constant
melting point,
87-8°.
Yield 11.2g, 56£.
380; Pound (In benzene) 373.
Analysis;
Mol. Wt. Calod*
Calcd. fo r
CggHggOgS C: 82.1; H; 9 .6 ; Pound C: 81.8; Hs 9.8.
A lg sample of th is m aterial was dissolved In 25cc of
anhydrous ether In a t e s t tube and a dry hydrogen chloride
bubbled through the so lu tio n .
The solution became cloudy
and eventually droplets of water could be seen on the sides
of the te s t tube.
had evaporated.
The gas was run In u n til a l l the ether
A yellow so lid remained in the te s t tube.
This so lid was re c ry s ta lliz e d from methanol, melting 73-4°
and glvii^s a p ositiv e t e s t for halogen when fused with
8odium.
58
A sample of th e m ateriel wee then run In the Grlgnard
“machine".
At room temperature I t evolved 1.34 equivalents
of methane (enolination of keto group) and a t the boiling
point of dibutyl ether I t evolved an additional 0.75
equivalents (hydrogen of t e r t ia r y hydroxyl group).
7. Preparation of beta-Keto-gamoa,gamma-dlneopentylb utyric Acid, [ (CH^CCHgJgCHCOCHgCOOH.
Into a 0.1 Msolution of the bromomagneslum enolate of
dineopentylcarbinyl methyl ketone was bubbled, with s t i r ­
rin g , a stream of dry carbon dioxide gas.
flask was immersed In an ic e - s a lt bath.
The reaction
The carbon dioxide
was run in u n t i l the mixture became too viscous for fu rth e r
stirrin g *
The coolir^ bath was removed and the mixture
d ilu ted with lOOcc of anhydrous e th e r.
The material was
then poured onto an lc e -su lfu rio acid mixture.
The ether
layer and ether ex trac ts were then combined and shaken with
2O0cc of 20j6 cold sodium hydroxide solution.
The water
layer was then removed and a c id ifie d with cold d ilu te s u l­
fu ric aoid.
The white cry sta ls which separated were f i l ­
tered, washed with water and re c ry s ta lliz e d from methyl
alcohol.
The yield of m aterial was 12.2g, 49%.
A 3g
sample of the m aterial was dissolved in 5co of ether and
placed In a small bulb with a c a p illa ry e x i t .
The ether
was removed on the steam bath and then the solid residue
heated with a small flame.
When the material began to de­
compose, the end of the cap illa ry tube was dipped into a
59
fre sh ly prepared lime water so lu tio n .
Hie solution became
cloudy during the decomposition of the acid.
When the
m aterial had a l l melted and no fu rth e r evidence of decompo­
s itio n was apparent, the bulb was broken and the liquid
f ilte re d o ff.
1.4558.
The index of the re s u ltin g m aterial was
This Is the Index of the dineopentylcarbinyl
methyl ketone.
The acid on standing a t room temperature
slowly deconq?osed.
I t melted a t 84-5° with deoosqposltion.
Neutral equivalent of the acid:
245.
Calculated 242.
Pound 244,
Mol. wt. Calculated 242; Pound (in bensene) 250.
8. Attempted Alkylatlon of the Enolate with Methyl Iodide.
In to a 0.5 Mso lu tio n of ethylmagneslum bromide was
added 40g (0.2 M) of dineopentylcarbinyl methyl ketone.
The mixture was s tir r e d u n ti l the evolution of gas had
ceased.
To th is mixture was then added 57g (0.4 M) of
methyl Iodide.
The mixture was then refluxed on the steam
bath f o r ten days, protected from the a i r by a s u lfu ric
acid tra p .
At the end of th is time I t was worked up in the usual
manner and the dry eth er solution placed under Column I I ,
the eth er stripped o f f , and the residue fractionated a t
SOasn.
The following cu ts were taken:
60
Cut
Col.
Temp •
Head
Temp.
1
126
110
6:1
1.4370
2.4
2.4
2
118
HO
6:1
1.4370
2.5
4.9
3
121
116
6:1
1.4372
2.7
7.6
4
121
117
6:1
1.4360
2.3
9.9
5
121
119
6:1
1.4360
2.3
12.2
6
121
119
6:1
1.4358
2.2
14.4
7
121
119
6:1
1.4360
2.5
16.9
8
121
119
6:1
1.4358
2.4
19.5
9
122
120
6:1
1.4358
2.3
21.6
10
122
120
6:1
1.4355
2.2
23.8
11
122
120
6:1
1.4356
2.8
26.6
12
122
120
6:1
1.4360
2.6
29.2
13
124
122
6:1
1.4360
2.0
31.2
14
126
124
6:1
1.4562
2.7
33.9
15
128
125
6:1
1.4372
2.4
36.3
Reflux
Ratio
Ref.
Index
Weight
Total
Weight
high index of Cut 8 1 to 3 is probably due to a small
int of methyl iodide , index 1.5290.
The only evidence
ilkylation is found in the l a s t out •
F. Preparation of Dineopentylcarbinyl Ethyl Ketone,
[ (CH3 )3CCH2 ]gCHCOCH2CH3 .
To a solution of 2.46 M of ethyluegnesium bromide die*
solved in 300cc of anhydrous ether was added with 109g
(0,5 M) of dineopentylacetyl chloride,
20
n
D 1•4430*40.
b.p. 109° at 20mm,
During the addition there was a rapid
61
evolution of gas.
After the addition was complete the mix­
ture was s tir r e d for twelve hours.
I t was then poured onto
an Ic e -s u lfu ric acid mixture.
The water layer was drawn
off and extracted with e th e r.
The e x tra c t was added to
the o rig in a l eth er layer,
washed with water,
the combined ether so lution
and dried over anhydrous potassium
carbonate.
The dried ether solution was decanted from the drying
agent and the ether removed on the steam bath through a
25cm Indented column.
The residue was then fractio n ated
through Column I a t 27mm.
Head
Temp.
The following cuts were taken:
Cut
Col.
Temp.
1
lOO
95
10:1
1.4378
2.3
2.3
2
129
125
10:1
1.4370
3.1
5.4
3
128
126
10:1
1.4380
3.8
9.2
4
128
125
10:1
1.4380
3.2
12.4
5
128
126
10:1
1.4380
3.4
15.8
6
128
126
10:1
1.4380
3.3
19.1
7
128
126
10:1
1.4380
3.9
23.0
8
128
126
10:1
1.4380
3.8
26.8
9
128
126
10:1
1.4378
3.4
30.2
io
128
126
10:1
1.4378
3.2
32.4
11
128
126
10:1
1.4379
3.3
35.7
12
128
126
10:1
1.4380
3.1
38.8
Reflux
Rati o
Ref.
Index
Weight
Total
Weight
62
Cut
Col.
Temp.
Head
Temp.
Reflux
Ratio
13
128
126
10:1
1.4380
3.0
41.8
14
128
126
10:1
1.4380
3*3
45.1
15
128
126
10:1
1.4378
3*7
48*8
16
128
126
10:1
1.4378
3*6
52.4
17
128
126
10:1
1.4379
3.9
56.3
18
128
126
10:1
1.4379
3.7
60.0
19
128
126
10:1
1.4378
3.8
63.8
20
128
126
10:1
1.4379
3.6
67.4
21
128
127
10:1
1.4380
3.0
70.4
22
128
127
10:1
1.4378
3.1
73.5
23
128
130
10:1
1.4380
3.0
76.5
24
128
130
10:1
1.4381
3.5
80.0
25
128
131
10:1
1.4383
3.5
83.5
26
128
131
10:1
1.4401
3.9
87.4
A ta rry resid u e,
Ref.
Index
Total
Weight
10.3g, giving a po sitiv e enol t e s t
with f e r r ic chloride was obtained.
obtained in 82^ yield*
Weight
The ethyl ketone was
An attempt to make an oxlme In a
sealed tube at 125° for twenty-four hours was unsuccessful*
No fu rth e r attempt was made, although i t Is quite possible
th a t longer heating might produce a derivative*
A Zerevitinov determination was run in the Grlgnard
"machine"•
A q u a n tita tiv e evolution of methane gas and
no addition was obtained* (46)
65
G. Reactions of Dineopentylcarbinyl Ethyl Ketone
1, Reaction of Dineopentylcarbinyl Ethyl Ketone with
Sodium Hyiroxide.
A mixture of llg
(0*05 M) of dineopentylcarbinyl
ethyl ketone and 50cc of 25^ sodium hydroxide was refluxed
on a hot p la te fo r twenty-four hours.
Hie solution was
cooled, neutralized with an ice water solution of 20^ su l­
fu ric acid and extracted with e th e r.
The ether solution
was dried over anhydrous sodium s u lfa te , the solution de­
canted from the drying agent, and the ether removed
through Column I I .
Hie residue was fractio n ated a t 20mm.
The following c u ts were taken:
Cut
Col.
Temp .
Head
Ten*>.
Ref. Index
1
112
117
1.4569
0.8
0.8
2
114
117
1.4376
1.1
1.9
3
114
137
1.4378
0.9
2.8
4
114
117
1.4380
1.3
4.1
5
114
117
1.4380
1.5
5.6
6
114
117
1.4381
1.8
7.4
7
116
118
1.4380
1.9
9.3
8
115
118
1.4382
0.6
9.9
Weight
Total
W ei^t
Residue l . l g
This represents a t le a s t an 83^ recovery of unchanged
ethyl ketone.
64
2 . Preparation of the Monobromoketone,
[ (CH3 )5CCH2]2CHC0CHBrCH5 .
To 21g (0.1 M) of dineopentylcarbinyl ethyl ketone In
a 200cc three neok flask with mercury seal s t i r r e r , dropping
funnel, and reflux condenser, was added with s tir r in g 16g
(0*1 M) of Doer *s bromine.
The reaction was so vigorous
th a t the mixture was cooled In an Ice bath.
The reactio n
seemed to be catalyzed by one of the reactio n products,
since I t became noticeably more rapid as I t proceeded.
When a ll the bromine was added, the mixture was shaken
with water, the heavy o il separated and washed with d ilu te
sodium carbonate solution, d ilu te sodium th lo su lfa te solu­
tio n , and water successively.
The conqpound was then dried
over anhydrous potassium carbonate.
This oonpound Is very unstable.
standing fo r one day.
I t becomes colored on
I t cannot be fraotlonated without
decomposition even at lmm of pressure.
However, I f I t
is
d i s t i l l e d a t lnza through a small column such as Column I I ,
as rap id ly as possible,
of p u rity .
I t may be obtained In a f a ir degree
The decon^osltlon evidently Involves dehydro-
halogenation,
since the product of decomposition gives a
negative halogen t e s t and absorbs bromine without the evo­
lu tio n of hydrogen bromide.
This phase of the problem,
however, was not further investigated.
65
By th is method of rapid d i s t i l l a t i o n was obtained 20g
of m aterial, b .p . 90° a t lam, n2°D 1.4665*
Analysis:
Halogen
Calcd. for Br: 27.5#; Pound 26.4#.
Yield 68.9#.
3. Reaction o f Dineopentyloarbinyl Bthyl Ketone with
Sodium Hypobromite.
In a 500co three neek fla s k , equipped with mercury
sea l s t i r r e r ,
dropping funnel, and reflu x condenser, was
placed 200cc of an ice water solution of 16g (0.4 M) of
sodium hydroxide.
The fla sk was surrounded by an Ic e - s a lt
bath and s tir r e d for t h i r t y minutes.
At the end of th is
time the dropping funnel was charged with 32g (0.2 M) of
Dow's bromine.
The bromine was added slowly with vigorous s tir r in g
to the sodium hydroxide solu tion , keeping the flask and
contents cold during the ad d itio n .
When a l l the bromine
had been added, the mixture was s tirre d for an additional
hour.
Hie ethyl ketone s o lid if ie s well above the tempera­
ture of such a mixture.
Accordingly, llg
(0.05 M
) of the
ketone was dissolved in 50cc of dloxane and th is solution
added to the sodium hypobromite dropwise with s t i r r i n g .
When a l l the dloxane solution was added, the mixture
was s tir r e d fo r fo rty -e ig h t hours, allowing i t
room temperature.
to come to
I t was then steam d i s t i l l e d u n til no
more o ily drops came over with the steam.
66
The resid ual alkaline solution was acidified with
d ilu te su lfu ric acid*
There was no organic material
Isolated from th is acidified mixture.
was extracted with 200cc of ether.
The steam d i s t i l l a t e
The ether solution was
washed with ten portions of lOOcc of water, su ffic ie n t
ether being added a f te r each washing to keep the volume
of ether solution a t 200cc.
In th i s way almost a l l the
dloxane was removed from the e th e r.
The ether solution was dried over anhydrous potassium
carbonate and the ether removed through Column II a t 20mm.
The residue gave a positive halogen t e s t .
The materiel
did not so lid ify on standing, contrary to expectations.
I t was accordingly d i s t i l l e d through Column II
The following cuts were obtained:
Cut
Col• Tenp •
Head Tenp •
Ref. Index
1
78
81
1.4388
3.3
2
85
90
1.4601
H
3
87
90
1.4660
o»
rapidly as possible.
at 1mm as
4
87
90
1.4663
3.4
.
to
6
H
Black residue
Weight
2.0
The Index and boiling point Indicate th at the product
of th is reaction i s
the monobromoketone.
Yield 45.5^.
A
longer reaction time and a larger quantity of sodium hypo­
bromite might possibly produce the dibrorao compound.
67
4. The Reaction of Dineopentyl earblnyl Bthyl Ketone with
t-ButylmagnesIum Chloride*
To a 0*1 M solution of t-butylmagnesium chloride was
added with s t i r r i n g
eth y l ketone*
21g (0.1 M) of dlneopentylcarblnyl
The gas which, was evolved during t h i s addi­
tio n was led through trap cooled in an I c e -s a lt bath and
then bubbled through a d ilu te solution of potassium per­
manganate*
The potassium permanganate solution was not
decolorized*
After a l l
was s tir r e d overnight*
the ketone was added, the solution
Next morning i t was poured onto an
ic e - s u lf u r ic acid mixture and worked up In the usual manner*
The dried eth er solution was plaoed under column I I
and the eth sr
stripped off at atmospherlo pressure.
residue was then fractio n ated a t 20mm.
The following cuts
Cut
Col.
Temp •
Head
Temp •
Ref.
Index
1
113
111
1.4367
1.8
1.8
2
113
114
1.4374
1.4
3.2
3
113
116
1.4378
2.1
5.3
4
113
115
1*4380
2.4
7.7
5
113
115
1.4379
•7
•
01
10.1
6
113
115
1.4330
2.6
12.7
7
113
115
1.4330
2.3
15.0
8
113
115
1.4381
to
•
■
*
3
>taken:
17.7
9
114
116 1.4383
Residue
0.6
l.lg
Weight
The
Total
Weight
18.3
68
This represents an &1% recovery of ketone*
There i s
no evidence of any other produot.
H. Reactions of the Bromoroagneslum Enol&te of
Dineopentylc&rblnyl Ethyl Ketone.
1* The Gilman Grignard Test*
To a 0*05 M solution of ethylmagneslum bromide d is­
solved in lOOco of anhydrous ether was added with s tir r i n g
21g (0.1 M
) of dineopentylcarblnyl ethyl ketone*
The solu­
tion was s tir r e d fo r twenty-four hours a t reflux tempera­
ture a f te r the ad ditio n was complete*
The solution was
oooled and a 0.5cc sample was removed and subjected to the
Gilman Grignard test*
The sanple gave a strongly positive
te s t *
2. Preparation of 1 ,1-Bis-(dineopentylacetyl)-ethane,
CCH212CHCOCHCH3GOCH*CH2C(CH3 ^3 ^2 #
To a 0*02 M solution of ethylmagneslum bromide was
added 4.24g of dineopentylcarblnyl ethyl ketone.
tio n was accompanied by the evolution of gas.
The addi­
When a l l the
ketone was added the mixture was s tir r e d u n til the magnesium
enolate precipitated*
To th is was added 4.3g of dineo-
pentylacetyl ch lo rid e.
The mixture was s tir r e d with heat­
ing for twenty-four hours*
I t was then deoonposed in the usual manner.
The ether
was evaporated on the steam bath and the residue d i s t i l l e d
through a Claisen flask*
The solid collected was
69
c r y s ta llis e d from methyl alcohol, m.p. 86-7°.
was 3.6g,
49^.
with f e r r i c
The yield
The crystals gave a p o sitiv e enol te s t
chloride.
Molecular Wt* Calculated, 380;
Pound (in benzene) 391.
C, 79.2; H, 12.7.
Pound:
Analysis:
Calod. for C©aHcaOa :
*D 50 2
C, 79.0; H, 12.7.
3. Preparation of alpha-Methyl-beta-keto-gaosna,gamma—
dlneopentylbutyrlo Acid, [ (CH^^CCHg^CHCOCHCCI^COOH.
To a 0.05 M solution of ethylmagneslum bromide In a
lOOco of anhydrous ether was added with s t i r r i n g llg
(0.05 M) of dineopentylcarblnyl ethyl ketone.
was accompanied by a vigorous evolution of gas.
Hie addition
The mix­
ture was s tir r e d overnight during which time the enolate
separated as white o ry s ta ls .
In to t h i s mixture was added
24g (1.0 M) of so lid carbon dioxide.
The mixture was
allowed to a l t u n til a l l the dry ice had disappeared.
At the end of t h i s time the mixture was poured onto
an Ic e -s u lfu ric acid mixture,
extracted with eth er,
ether e x tra c t washed with water,
the
and then with 25cc of 10%
8odium hydroxide.
The sodium hydroxide layer was separated and heated to
remove the e th e r.
fu ric ac id .
I t was then ac id ifie d with d ilu te su l­
The so lid separating was f il te r e d by suction
and re c ry s ta lllz e d from methyl alcohol to constant melting
point,
89-90°, with evolution of gas.
70
A 2g sample was heated and the gas evolved led Into
lime water.
A white p re c ip ita te of calcium carbonate
confirmed the presence of carbon dioxide.
residue showed a re fra c tiv e
The liq u id
index at 20° of 1.4378. the
index of the dineopentyloarblnyl ethyl ketone.
acid 6.4 (48£).
Neutral equivalent:
Yield of
Calcd. for
*C6H11^2CHCOCHCH3COOH# 256; Found 2 b s » 264*
4. Preparation of 1-Dlneopentylacetyl-l-benzoylethane.
t ( CHg) 3 c c h 2 ] 2 c h c o c h ( c h ^ ) c o c 6 h 5 .
To a 0.05 Msolution of ethylmagneslum bromide d lssolved in anhydrous ether was added l l g
neopentyloarblnyl eth y l ketone.
added the mixture was s tir r e d
(0.05 M) of d i­
When a l l the ketone was
overnight.
The next morning 7g (0.05 M) of Sastman Kodak White
Label benzoyl chloride was added with s t i r r i n g .
The mix­
tu re was then decomposed by pouring onto an ic e -su lfu ric
acid mixture ex tractin g with eth er and washing the ether
e x tra c t with d ilu te potassium carbonate.
The ether solution was dried over anhydrous potassium
carbonate mud the ether removed under Column I I .
The o ily
residue was then heated under reduced pressure u n t i l the
benzoyl chloride and ethyl ketone were removed.
residue s o lid if ie d on cooling.
The pot
The resulting solid was reorystallised from nwthyl
alcohol to a constant m.p. 81-2°.
Yield 6.0g, 39jt.
Molecular weight, Calculated 316; Pound (in benzene) 323,
326.
A 5g sample of the material was heated at reflux for
six hours in a 125cc flask with 20cc of 60% sodium
hydroxide.
The solution was cooled, diluted with 50oc of
water, and extracted with ether.
The ether extract was
dried and the ether removed under Column I I .
was fractionated through Column I I .
The residue
A to ta l of 1.9g of
material, b.p. 114-6° at 20wm, n20D 1.4376 was obtained.
This represents a 69% yield of dineopentyloarblnyl ethyl
ketone.
The alkaline water solution was acidified with dilute
sulfuric acid and filte re d .
The white crystals were re-
crystallized from boiling water, melting point 121-3°, no
depression when mixed with an authentic sanple of benzoic
add.
Yield l.&g, 69%.
5. Preparation of Phenyl-(alpha-methyl-beta-keto-gamma,
gamna-dine ope ntylpropyl) - oarbinol,
[(C H 3 ) 3 C C H g ] 2 CHC0CH (CH5 )C H 0H C 6 Hg .
To a 0.05 M solution of the bromoraagneslum enolate of
dineopentyloarblnyl ethyl ketone, prepared in the usual
way was added 6g (0.05 M
) of freshly d is tille d Eastman
White Label benzaldehyde, dissolved in 25cc of anhydrous
72
e th e r .
The mixture was heated a t r e f lu x fo r six hours
deooaqposed In th e usual fash io n .
The e th e r so lu tio n was
d rie d over anhydrous potassium carbonate and the ethor
removed through Column I I .
The re sid u e was then heated a t 60° fo r t h i r t y minutes
under a pressu re of 20mm.
the pot re s id u e s o l i d i f i e d .
On cooling to room tem perature,
The s o lid resid u e was r e -
e r y a t a l l l s e d from methanol to co n sta n t m.p. 82-3°.
8»7g# 54^,
Yield
Mol. Wt. Calcd. 317; Pound (In benzene) 321.
323.
A l.O g sample was oxidized w ith l.Og of chromic oxide
in 2&oe of 9
acet i c a c id .
the u s u a l fa sh io n .
A to ta l
81-2° was o btain ed .
The product was Is o la te d In
of 0.6g of m a te ria l,
This m aterial
melting
showed no depression
w ith a sample of the 1,3-diketone prepared above.
sample o f th e unoxldlsed k eto -alco ho l i t
With a
gave a mixture,
melting 63-78°.
6. P rep aratio n of Diphenyl-(alpha-methyl-beta-keto-gainraa,
gamma-dineopentylpropyl)- c a r b ln o l,
[ ( CH3 ) 3 CCH2 J g C H C O C H ( C H ^ ) C O H ( C g H g ) 2 .
To a 0.05 M so lu tio n of the broraomagnesium en o late of
dineop enty loarb ln yl e th y l ketone was added 9g (0.05 M) of
Eastman White Dabel bensophenone, d isso lv ed In 25cc of
anhydrous e th e r .
Ihe mixture was re fluxed fo r twelve hours
and decomposed in the usual manner.
The eth e r so lu tio n of
75
the product was dried over anhydrous potassium carbonate
and the ether remowed through Column I I .
ether was removed,
When a l l the
the residue s o lid if ie d .
The product
was re c ry s ta lliz e d from methanol, m.p. 122-5?
60*.
Mol. Wt. Calcd. 594; Pound 534, 588.
Yield 12g,
Analysis:
Calod. fo r C27H3802, C: 82.2; H: 9 .6 ; Pound C: 82.0;
H: 9 .7 .
A 0.2g sample of the product was dissolved In 25co of
anhydrous e th e r.
Into t h i s solution was bubbled a stream
of dry hydrogen chloride gas.
A cloudiness appeared and,
on continued heating, d ro p lets of water separated.
The
hydrogen chloride was run In u n ti l a l l the ether had
evaporated, th e yellow residue dried by f i l t e r i n g , and
c r y s ta llis e d from methanol, m.p. 110-1°.
The nmterlal was
yellow and gave a po sitiv e halogen te s t .
A sample of the t e r t i a r y carblnol was run in the
Grignard "machine".
At roam temperature i t
evolved 1.14
equivalents of methane and a t the boiling point of dlbutyl
ether I t evolved an additional 0.89 equivalents.
I . Preparation of Dineopentyloarblnyl Phenyl Ketone,
[ ( ch5 )3 cch2] 2coc6h6 .
A solution of 0.48 M of phenylmagneslum bromide d is ­
solved in lOOec of anhydrous ether was added with s t i r r i n g
to llOg (0.5 M) of dineopentylacetyl ch lo rid e.
The re ­
sulting mixture was s tir r e d with heating for twenty-four
74
hours•
th* end of t h i s time the mixture was cooled and
poured onto an Ice*sulfuric acid mixture.
I t was then
worked up in the manner previously described.
nie dry eth e r solution obtained was placed under
Column I and the ether removed under reduced pressure*
The
c ry s ta ls which separated when the ether was removed were
f i l t e r e d and re c ry s ta lliz e d from methanol, melting point
64-5°; y ield llOg, 84*.
Molecular Weights Calculated 560;
Pound (in benzene) 568.
In the Grignard "machine" the
ketone showed q u an titativ e addition with no enollzatlon.(46)
The compound did not give a ketone derivative with
2,4-dinitrophenylhydrazine or hydroxyl amine •
I t s ketonio
nature was estab lish ed , however, by i t s reaction with
methylmagneslum iodide.
J . The Reactions of Dineopentyloarblnyl Phenyl Ketone
1. Attempted Bromlnation of Dineopentyloarblnyl Phenyl
Ketone•
In a 125oo Bhrlenmeyer flask was plaoed a mixture of
6.5g (0.025 M) of dineopentyloarblnyl phenyl ketone, 25oe
of earbon te tra c h lo rid e , and 8g (0.05 M) of Dos’* bromine.
The fla s k was f i t t e d with a reflux condenser and the mix­
ture heated at 80° for ten hours.
The mixture was then
washed with water, d ilu te potassium carbonate solution,
d ilu te sodium th io s u lfa te solution, and water successively.
Xt was tto n d ried over anhydrous potassium carbonate.
The dry solution s t i th ss plaoed undsr Column I I sad
heated a t SOmm to rtaovi tha oar bon te tra c h lo rid e .
s o lid rssid u a was r e e r y s ta llls e d from methanol.
The
All tbs
c ry s ta ls obtained s e l t t d 64-5° and. gave a negative halogen
te st*
The mother liquor was evaporated to dryness and the
residua te s te d far halogen by a sodium fusion.
residue gave a negative t e s t .
covered.
Even the
A t o t a l of 6.2g was r e ­
Since the d if f ic u lty of bromination was cle a rly
estab lish ed by th is method, no fu rth e r attempt was made
to prepare the bromoketone •
2. Attempted Oxidation of Dineopentyloarblnyl Phenyl Ketone.
A mixture of 6.5g (0.025 M) of dineopentyloarblnyl
phenyl ketone. lOg (0.1 M) of chromic oxide, and lOOcc of
95% a c e tic acid was placed In a 250cc Bhrlenmeyer fla s k .
The mixture was allowed to s i t a t room temperature for
twenty-four hours.
with water.
A Sec sample was removed and d ilu ted
There was no green color to Indicate oxidation.
The mixture was then heated a t 60° for an additional
nineteen hours.
A sample was again removed and showed no
in d icatio n of oxidation.
The mixture was then heated for
an ad d itio n al nineteen hours a t 85°.
The solution a t th is
point was green In c o lo r.
The mixture was then cooled and diluted with 500cc of
water arwi extracted w ith e th e r.
The ether solution was
76
vt«h*d with wtt*r i e w a l
times to remove the ehromlo
oxide end the a c e tic acid .
The ether solution was then
extracted with 50cc of 10# sodium hydroxide.
The alkaline
1 » 7 « was separated, heated to remove the eth er, and
a c id ifie d with d ilu te s u lfu ric acid.
There was no organic
m aterial obtained from the a c id ifie d solution.
The eth er so lu tio n , a f te r extracting with a lk a li, was
dried over anhydrous potassium carbonate and the ether
evaporated.
The so lid residue was re o ry s ta llls e d from
methanol, melting p o in t 64-5°.
m aterial was obtained.
A t o t a l of 6.0g of sta rtin g
No other products were found.
5. Reaction of Dineopentyloarblnyl Phenyl Ketone with
Methylmagneslum Iodide.
To a 0.1 M solution of methylmagneslum iodide In lOOoc
of anhydrous dlbutyl eth er was added with s t i r r i n g a solu­
tio n of 15.0g (0.05 M) of dineopentyloarblnyl phenyl ketone
in 25oc of anhydrous e th e r.
The re s u ltin g mixture was
heated a t reflu x for twelve hours, being protected from
moisture by a su lfu ric acid trap .
At the end of t h i s time the mixture was cooled and
poured onto Ice.
The water layer was separated and ex­
tra c te d with d iethyl e th e r.
The e x tra c t was added to the
d ib u tyl e tto r layer and the mixture washed with sodium
th io s u lfa te and dried over anhydrous potassium carbonate.
The ether was removed through Column IX, the d ieth y l ether
77
at atmospheric pressure and the dibutyl ether a t 20ina.
The residue was d i s t i l l e d through a Clalsen fla s k , the
portion b o ilin g a t 140-5° a t 5mm was oolleeted and placed
overnight in the Ice box.
The c ry sta ls which separated
were f il te r e d and re ery stal lized from methanol.
A to t a l
of 8.4g, 61% y ie ld , of m aterial, smiting 42-3° was obtained.
Molecular Weight Calod. 276; Pound (in benzene) 284.
Analysis:
Calcd. for C19H32°* Cs 82.6; Hx 11.6; Pound
C: 82.4; H: 11.5.
In the Grignard "machine" the oompound evolved one
equivalent of methane gas.
one active hydrogen.
This indicates the presence of
A lg sample, on oxidation a t room
teog>erature with lg of chromic oxide in 55cc of 96% aoetlc
acid,
yielded 0.6g of the phenyl ketone, m.p. 63-4°, no
depression with a sample of the phenyl ketone prepared as
previously reported and 0.17g of an acid, melting 134-6°.
Further confirmation th at the compound which was oxidized
i s dineopentylcarbinylmethylphenylcarbinol,
t(C H ^)
CCH2]gCHCOH(CH^)CgHg, and is n either dineopentyl-
carbinyl-o-1olylcarbinol, [ (CH^>3CCH2 )2CHCH0HC6H4 ( ) ( o- ),
nor dlneopentylcarbinyl-p- to ly lcarb in o l,
HCH3 )3CCH2 ]2CHCH0HC6H4 (CH3 )(p -), i s found in the produots
of the oxidation of the to ly l ketones reported below.
1
K. Preparation of Dineopentyloarblnyl o-Tolyl Ketone,
I (CHg)5CCHg]gCHCOC6H4 (CHj) ( o -).
To 54g (0.25 M) of dineopentylacetyl chloride was
added with s t i r r i n g a solution of 0.21 Mof o-tolylmagnesium
bromide in lOOcc of anhydrous e th e r.
heated a t reflu x for ten hours.
ic e .
The mixture was
I t was then poured onto
The water layer was separated, extracted with ether,
the ex tract added to the main body of ether solution, and
the whole solution dried over anhydrous potassium carbonate.
The dry eth er solution was placed under Column II and
the ether removed at room temperature under reduced pres­
sure.
The residue was d i s t i l l e d from a Claisen at 5mm.
The m aterial boiling 100-40° was collected and placed in
the ice box.
The crystals which separated a fte r standing
overnight were f ilte r e d through a cold f i l t e r .
material melts 32-3°.
The pure
This low melting point makes puri­
fic a tio n very tedious,
a
to ta l of 33g, 61#, of crude
material was obtained.
Prom th is by continued chilling
and f i l t e r i n g were obtained l l g of pure m aterial.
The
tedious p u rific a tio n was discontinued when su fficien t
m aterial fo r experimental study was obtained.
Moleoular
Weight Calcd. 274; Pound (in benzene) 283.
A sample of the material was placed in the Grignard
"machine” .
Like the phenyl ketone, i t showed quantitative
addition of methylmagneslum bromide. (46)
L. Reactions of Dineopentylcarbinyl o-Tolyl Ketone.
1. Attempted Bromlnatlon of Dineopentyloarblnyl o-Tolyl
Ketone.
A mixture of 6.9g (0.025 M
) of dineopentylcarbinyl
o -to ly l ketone,
25ec of carbon tetrao hlo ride, and 8g
(0.05 M) of Dow’b bromine was placed in a 125cc Ehrlenmeyer
fla sk ,
f itte d with a reflux condenser, and heated at 80°
fo r ten hours.
The mixture was cooled and shaken with
water, d ilu te potassium carbonate solution, d ilu te sodium
th io su lfa te solution, and water successively.
The solution
was then dried over anhydrous potassium carbonate.
The dry solution was placed under Column II and the
carbon tetrach lo rid e removed under 20mm pressure.
residue was placed in the ice box overnight.
The
The crystals
which separated were f ilte r e d and recry sta llize d from
methanol, melting 32-3°.
Cooling and f ilte r in g produced
a to ta l 5.6g of cy rstals melting 32-3° and showing no
depression when mixed with a sample of the dineopentyloarbinyl o -to ly l ketone.
halogen t e s t .
The oily residue gave a negative
Since th is reaction established the d i f f i ­
cu lty of bromlnatlon, no fu rth e r attempt was made to
bromlnate the ketone.
2. The Oxidation of Dineopentylcarbinyl o-Tolyl Ketone.
A mixture of lg of dineopentylcarbinyl o-to ly l ketone,
lg of chromic oxide,
and 25cc of 95# acetic acid was placed
80
In a 50oc Bhrlenmejer fla s k and l e f t a t room temperature
fo r twenty-four hours.
The mixture was then poured Into
lOOcc of water and ex tracted with e th e r.
The e th e r was washed repeatedly with water to remove
the chromic oxide and a c e tic acid ,
i t was then ex tracted
with 50cc of 10# sodium hydroxide.
The water layer was
separated and a c id if ie d .
A very small amount of m aterial,
m elting 104-139° was obtained.
Prom th e ether so lu tio n was obtained 0.6g of unoxidised
o - to ly l ketone.
Although extreme care was used In working
up th e m ixture, no tra c e of the phenyl ketone, which was
obtained In oxidising dineopentylcarbinylmethylphenylc a rb ln o l, could be found.
The same q u a n titie s of ketone, chromic oxide, and 95#
a c e tic acid were mixed in a 50cc Bhrlenmeyer and heated
a t 70° for seventy-two hours.
On working up in the same
manner as above, 0.5g of dineopentylcarbinyl o -to ly l ketone
melting 32-3°, was reoovered in the ether la y e r.
From th e
sodium hydroxide layer was obtained O.lg of m aterial melt­
ing 132-68° and 0.2g of dlneopentylacetic acid , melting
p oin t 87-89°.
Again there was no in d ic a tio n of the
presence of phenyl ketone.
81
M. Preparation o f Dineopentylcarbinyl p-Tolyl Ketone.
[ (CHg)^CCHg]2CHC0C6H4 (CHj ) (p - ) .
To 27g (0.126 M) of dlneopentylaoetyl chloride was
added with s t i r r i n g
a solution of 0.112 M of p -to ly l-
magneslum bromide in lOOce of anhydrous e th e r.
addition was ccomplete,
When the
the mixture was refluxed for
twelve hours.
The mixture was then poured onto an ic e -su lfu rlo aold
mixture and worked up In the usual fashion.
A to ta l of
26.3g of m aterial, melting point 78-9° was obtained from
th is re a c tio n .
This represents an
y ield .
Molecular
Weight Calculated: 274; Pound (in benzene) 285.
A sample of th is material was rim in the Grignard
"machine11.
Like the phenyl and o -to ly l ketones, I t showed
q u a n tita tiv e addition of methylmagneslum bromide.
N. Reactions of Dineopentylcarbinyl p-Tolyl Ketone.
1. Attenpted Bromlnatlon of. Dineopentylcarbinyl p-Tolyl
Ketone.
A mixture of 6.9g (0.025 M) of dineopentylcarbinyl
p - to ly l ketone, 25ce of carbon tetrac h lo rid e , and 8g
(0.06 M) of Dow1s bromine was placed in a 125cc Ehrlenmeyer
fla s k , f i t t e d with a re flu x condenser.
heated for ten hours a t 80°
The mixture was
82
The nlxtuTA was vashod with water, d ilu te potassium,
carbonate solution, d ilu te sodium th io su lfa te solution,
and water successively.
I t was then d ried carer anhydrous
potassium carbonate.
The dry so lution was plaeed under Column I I anti the
carbon te tra c h lo rid e removed a t 20mm.
The residue, a
s o lid , was dissolved in methanol and from th is solution
was obtained 6.6g of unchanged p -to ly l ketone, melting
point 78-9°.
The mother liquor was evaporated to dryness
and the residue tested far halogen by the sodium fusion
method.
The t e s t was negative.
2. The Oxidation of Dineopentylcarbinyl p-Tolyl Ketone.
To a mixture of lg of chromic oxide and 55cc of acetie
acid In a 50cc fla sk was added lg of dineopentylcarbinyl
p - to ly l ketone.
The mixture remained a t room temperature
fo r twenty-four hours.
The mixture was then d ilu ted with lOOcc of water and
ex tracted with e th e r.
The ether solution was washed re ­
peatedly with water to remove the chromic oxide and aoetlc
acid.
I t was then ex tracted with 50oc of 10# sodium
hydroxide.
sodium hydroxide ex tract was a c id ifie d with d ilu te
s u lfu ric sold and tte
filte re d
c ry s ta ls which separated out were
and washed with water.
The dry m aterial melted
85
o
a t 170-200 .
Only a very email amount of the material
vae obtained.
From the eth er layer was obtained 0.7g of unchanged
dineopentylcarbinyl p -to ly l ketone, melting point 78-9°.
There wae no phenyl ketone obtained.
The above oxidation was repeated using the same
q u a n titie s of m aterials but heating fo r seventy-two hours
a t 70°.
This oxidation yielded 0.4g of acid melting
189-198° and 0.3g of unchanged dineopentylcarbinyl p -to ly l
ketone.
Again, a carefu l search f a ile d to reveal the
presence of any dineopentylcarbinyl phenyl ketone, which
was obtained when dlneopentylcarblnylphenylmethylcarblnol
was oxidised.
0. The Preparation of Dineopentylcarbinylglyoxal,
[ ( CH3 ) 3 CCH2 ]g C H C O C H O .
A solution o f 6.5g (0.018 M) of the pyridinlum s a l t of
dineopentylcarbinyl bromomethyl ketone, melting point 214-6P,
and 3g (0.02 M) of p-nitrosodlm ethylaniline In 270co of
ethanol was cooled in an ic e - s a lt bath to 5°.
While s t i l l
cold, lOcc of 1H sodium hydroxide was added in small por­
tions with shaking.
The odor of pyridine was very strong
a t th i s p o in t.
The so lid which separated was f il te r e d and dissolved
in lOOcc of e th e r.
The ether solution was washed
84
repeatedly with 2 H hydrochloric acid u n t i l the water layer
was fre e from any oolor*
of 25eo each*
This required th irte e n washings
The ether solution was then washed once with
water and once with d ilu te potassium carbonate solution and
d ried over anhydrous sodium sulfate*
The dry ether solution was then decanted from the dry­
ing agent and the eth er removed under reduced pressure.
The c ry s ta ls which separated were re c ry s ta llis e d from
methanol, melting point 114-5°.
Yield 2«4g, 62^*
A sample of th is material gave a positive aldehyde
t e s t with ToH en 'a reagent and a positive aldehyde te s t
with P ehling’a reagent.
A sample of the m aterial formed
a 2,4-dinitrophenylhydrasone derivative
reagent*
on shaking with
The d erivative melted 135-8°.
P. Reactions of 1,3-Diketones
1* A lkylstlon of 1,3-Diketonea
a* The Methylation of Bis-(dineopentylacetyl)-methane.
In lOOcc of anhydrous ether was placed l*2g (0.05 M)
of very fin e ly divided m etallic sodium.
To th is was added
18g (0*05 M) of bis-(dineopentylacetyl )-methane, melting
96-7°*
When the evolution of gas had ceased, the mixture
was placed on the steam bath, the ether d i s t i l l e d o ff, and
lOOcc of anhydrous dioxane added.
86
To th i s dioxane solution was added 15g (0.1 M) of
methyl iodide.
The solution was then heated on the steam
bath fo r fiv e days, being protected
from moisture with a
s u lfu ric
large deposit of sodium
acid tr a p «
At th is time a
iodide had separated and a saiqple of the solution was
n e u tra l to moist litm us.
The solution was then decanted from the so lid ,
shaken
with d il u te hydrochloric aoid, extracted with ether, and
the ether solution dried over anhydrous sodium s u lfa te .
The ether and dioxane were removed under reduced pressure.
The residue c r y s ta lliz e d .
From th i s crude m aterial was obtained, by r e c r y s ta llization from methanol, 15g of c ry sta ls melting 86-7°.
rep resen ts a y ie ld of 80#.
This
The m aterial showed no depres­
sion in melting point when mixed with a sample of 1,1-bis(dlneopentylacetyl)-ethane, prepared from the enolate of
the eth yl ketone.
406.
Analysis:
Pound:
Mol. Wt.:
Calcd. 394; Found (in benzene)
Calcd. for C26H490g:
C 79.2; H 12.7;
C 79.0; H 12.7.
b. The Attempted Ethylation of Bis-(dineopentylacetyl)-methane.
Proceeding as in the raethylation described above, the
sodium enolate of b i s - (dineopentylacetyl)-methane was p r e ­
pared in the same molar quantity.
placed wit h dioxane,
After the ether was r e ­
llg (0.1 M
) of ethyl bromide was added.
86
This mixture was hsatsd as before on the stsam bath*
At
the and of five days there was no v is ib le deposit of
sodium bromide*
The heating was continued for five more
days without any indication o f reaction*
When the mixture
was worked up by the procedure previously described, a
q u a n tita tiv e recovery 10.6g of unchanged bis-(dineopentylacetyl)-methane was obtained, melting 96-7° without depres­
sion when mixed with a sample of the compound which had
not been subjected to th is
treatment*
c # The Methylation of 1 ,1-B is-(dineopentylaeetyl)-ethane*
By means of the same procedure as described above lOg
(0*05 M) of 1 ,1-bis-(dlneopentylacetyl)-ethane was con­
verted to the sodium enolate*
The enolate was heated in
dioxane on the steam b ath with 8*6g (0*06 M) of methyl
iodide for eight days*
On working up in the manner
already described, 8g, 76# yield, of 2,2-bls-(dineopentyla c e ty l)-propane was obtained, melting 65-6°.
This compound
gives a negative enol t e s t with f e r r ic chloride*
Analysis:
Calcd. fo r Cg7H5202 : C 79*6; H 12.7; Pound C 79.8; H 12.8.
A sample of th is m aterial was placed in the Orignard
"machine'*.
It
showed 65# enolisation and 136# addition.
d. The attempted Ethylation of 1 ,1-Bis-(dineopentylac ety l)-eth an e•
sodium enolate produced from lOg (0.03 M) of 1,1—
bis-(dlneopentylacetyl)-ethane was heated in dioxane with
87
6.6g (0*06 X) of othyl bromide fo r three weeks*
no Indication o f reao tlo n .
There was
The mixture on working up gave
a q u a n tita tiv e recovery, 9,6,
of unchanged s ta rtin g material,
e. The Methylation of Benzolydineopentylaeetylmethane.
By proceeding in the same manner as described for the
other methylations 7.5g <0,026 M) of benzolydineopentylacetylmethane was converted to 1-benzoyl-1-dlneopentylacetylethane in 73J* y ie ld , 5.7g.
The material melted 81-2°
and showed no depression when mixed with the product
obtained from the enolate of the ethyl ketone.
2.
The Bromlnatlon of Bis-(dlneopentylacetyl)-methane.
To a solution of 3.8g (0,01 M
) of b is - ( dineopentyl -
a c e ty l)-methane in 25oc of carbon tetrach lo rid e was added
with s t i r r i n g 1.6g (0.01 M
) of Dow»s bromine.
The reaction
proceeded smoothly with a steady evolution of hydrogen
bromide.
When a l l
the bromine had been added,
was s tir r e d overnight.
the solution
By morning a l l the bromine color
had been discharged.
The solution was washed with water, d ilu te potassium
carbonate so lu tio n , d ilu te
water successively.
sodium th io su lfa te solution, and
I t was then dried over anhydrous
potassium carbonate.
The carbon tetrach lo rid e was removed through Column I I
by d i s t i l l i n g at 20mm.
The solid residue was c ry sta lliz e d
88
from methanol to constant malting point 87-8°.
m aterial
Analysis:
The
gave a p o sitiv e halogen t e s t . Yield 4g, Q9%.
Calculated Br
17.4; Pound Br 16.5.
5 . The Action of Sodium Hydroxide on 1,3-Dike tone a.
th ree dike tones containing teo dineopentylcarbinyl
groups were treated with sodium hydroxide in an e f f o r t to
produce cleavage lik e th at obtained with benzoyldineopentylacetyl methane and l>benzoyl-l-dlneopentylacetylethane.
The
procedure in each case was as follows:
A 2g sample of the dlketone and 50cc of sodium hy­
droxide solution were placed In a 125cc Hhrlenmeyer flask
equipped with a re flu x condenser.
The mixture was heated
on a hot
p la te a t reflux for twenty-four hours.
The mix­
tu re was
then cooled and f i l t e r e d .
was ex­
The f i l t r a t e
tra c te d with eth er and the eth er evaporated.
There was
never any material found in th is ether e x tra c t.
The sodium hydroxide solution was then a c id ifie d with
d ilu te s u lfu ric acid .
(When very concentrated sodium
hydroxide solutions were used, these were diluted p rio r to
a c id ify in g .)
No organic m aterials were ever recovered from
these solutions.
In a l l eases the unchanged 1 ,3-dlketones were recovered
q u a n tita tiv e ly .
89
In the above manner bli* (dioeopentylaottyl)-asth&ne,
1 ,1-bla- (dlneopentylacetyl)-ethane, and 2 ,2-bis- ( dlneo­
pentylacetyl) -propane were each treated with 1%, 2%, 5%,
25%, 50%, and 60% sodium hydroxide solutions.
In the
treatment of these dlketones with 50% and 60% sodium
hydroxide,
the flasks were badly corroded by the a lk a li,
but the dlketones were completely unaffected.
90
Suggestions for Furthdr Investigation
1* The preparation of dineopentylcarbinyl mesityl
ketone should be r e la tiv e ly easy.
show a very in e rt carbonyl.
it
This confound should
With methyl Grignard reagent
seems to offer an excellent opportunity for demonstra­
tin g q u a n tita tiv e enolization involving the te r tia r y
hydrogen of the dineopentylcarbinyl group.
highly u n lik ely .
it
Addition seems
With highly branched Grignard reagents
affords an opportunity fo r comparison of the ease of
reduction with the ease of en o lization .
2. The dineopentylcarbinyl phenyl o -to ly l,
and p-
to ly l ketones should be treated with Grignard reagents.
These ketones offer an excellent opportunity for deter­
mining the e ffe c t of the Grignard reagent, i t s e l f ,
en o lizatio n .
on
With highly branched Grignard reagents, an
opportunity for comparison of the ease of addition; ease
of reduction; and ease of enolization is afforded by
these ketones.
3. The preparation of dineopentylcarbinylglyoxal by
the oxidation of the methyl ketone with selenium dioxide
should permit the preparation of th is compound in
reasonably large quantity.
The investigation of the re­
actions of th is compound in more complete d e ta il should
be very p ro fita b le .
♦• Til* preparation and properties of many 1,3-diketones ana aaally re alized fro a the broaoaagnosiua
anolataa of tha methyl and athyl ketones,
Th© hydrogena­
tio n of tha aa compounds might permit the preparation of
many very in te re s tin g compounds.
Adkins (47) has ahoam
th a t a wide v ariety of products can be obtained by auch
a procedure*
92
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