close

Вход

Забыли?

вход по аккаунту

?

код для вставки
Patented Aug. 30, 1949
2,480,649
I, UNITED STATES PATENT orrica
HOMOLOG OF VITAIWIN Be 7
Stanton A. Harris‘, West?eld, and Andrew N.'Wil
S011,
Colonia, N. .L, assignors to Merck & 00.,
Inc., Rahway, N. J ., a corporation of New Jersey
No Drawing.
Original application August 27,
1942, Serial No. 456,370. :Dividedsand this an
‘ ‘ plication July 20, 1946, Serial No. 685,239
’
5 Claims. I (chasm-297.5)
t
1
-
This invention relates generally to organic
(whichvvcanybe obtained by condensing equimo
chemicalcompounds and to methods of manu
facturing the same; in'a more limited sense, it
lecular proportions of methyl ethyl ketone and
methyl methoxyacetate in the presence of sodium
is ‘concerned with a growth-promoting factor re
at a low temperature) are added with a small
lated to pyridoxine (vitamin B6) and to proc- 5 amount of piperidine, to about 24.6 g. of cyano
esses for producing the same.
. The .present- application is a division of the co-
acetamide dissolved in approximately 100 cc. of
hot absolute ethanol. After cooling, the ‘precipi
pending application by the same inventors, ‘Serial 't'ated solid massvlis removed and washed with
No. 456,370, ?led August 27, 1942.,
"ethanol.
The present invention involves the synthesis 10' Approximately 119 g. of the Z-ethyI-Il-meth
of a novel organic chemical compound, 2—ethyl-'
oxymetliylé5-cyano-6-hydroxypyridine thus 0b
3-hydroxy - 4,5-bis-(hydroxymethyl)-pyridine, a
material which prevents or cures an acrodynia-
tained is suspended in acetic anhydride and
about 60.’? cc. of fuming nitric acid is added slow
like dermatitis in young rats and which possesses
1y,‘ while the mixture is vigorously agitated and
growth-promoting properties in the metabolism 15 maintained at a temperature of about 65-70“ C.
of plants.
Upon cooling a yellow crystalline solid appears.
The process according to the present invention
The solid and liquid are slowly poured into water
includes the condensation of cyanoacetamide
and the solid, which is the 3-nitro compound,
with l-methoxy-ZA-hexadione (which can be ob~
is removed, washed and dried.
tained by reacting methyl ethyl ketone and meth~ 30
About 76 g. of the 3-nitro-compound, 100 g. of
yl methoxy acetate), treatment of the 2-ethyl-
phosphorous pentachloride and approximately
3 - methoxymethyl - 5-cyano-6-hydroxypyridine
320 cc. of dry tetrachloroethane are mixed and
thus obtained with nitric acid, phosphorous
halide, and a reducing agent in succession to
heated upon an oil bath. After the reaction has
begun, as indicated by evolution of hydrogen
produce 2-ethyl-3-amino - 4 - methoxymethyl-éS- 25 chloride, the bath temperature is maintained at‘‘
aminomethyl pyridine, diazotization followed by
halogenation of the product, and hydrolysis of
the halogen compound to yield 2-ethyl-3-hy-
140-145” C. for about two hours, after which the
tetrachloroethane and phosphorous oxychloride
formed are removed by distillation under reduced
droxy - ‘L5 - bis- (hydroxymethyl) pyridine hydropressure at below 70° C. The residue is then dis
halide. The reactions involved can be repre- 3n solved in benzene and poured on crushed ice and,
sented as follows:
after being maintained at appromixately 0° C.
CNCHgONH-g
CH2OCH3
Na
I
ON HNOs
cHaoH2ooH3+ onloom?oom _-> cmon?cnu?‘omoom —»
o
o
oHeocHa
OzN
CN
CHaOCHa
P015
OzN
CN
CH20CHs
B:
——-v
CHaCH2\N/OH
-—->
CHsCHNN/OH
HCLHzN
CHzNHz-HCI
HNO:
——p
CH:CHz\N G1
I
——>
CHaCHz N
cmocm
CHzBr
HOOCHzOH
OHaCH:
N
H3!‘ H0
OHzBr Hi0
-—>
CHsCHa
onion
—\
.AgCl
N
HBr
,
HO
cHlon
CHaCH
HO]
I The following example illustrates a method of
carrying out the present invention, but it is to 70 for one hour, a slight excess of ammonia is added.
be understood that this example is given by way
of illustration and not of limitation.
Erample
About 38.4 ‘g. of 1-methoxy~2,4-hexadione 75
The benzene layer is removed, concentrated under
reduced pressure, extracted with petroleum ether
and the extract is then cooled, yielding a yel
low mass of 2-ethyl-3-nitro-4-methoxymethyl-5
cyano-G-chloropyridine.
The (i-chloro compound thus obtained is re
2,480,649
1. 2-ethyl-3-hydroxy-4,5 -bis- (hydroxymethyl) -
pyridine hydrohalide.
chloride of 2-ethyl43-amino-é-methoxymethyl-B
aminomethyl-pyridine.
4
We claim:
duced in methanol, using palladium black on
charcoal as a catalyst, yielding the dihydro
2. z-ethyl-3-hydroxy-4,5-bis- (hydroxymethyl) -
About 10 g. of the re
pyridine hydrochloride.
U
I
duced compound are dissolved in hot water, and
approximately 6.43 g. ofwsodium nitrite and 11.3 g.
of hydrochloric acid (36%) are added. After
2éethyl-3-hydroxy-4,5-bis- (halogenmethyl) -pyri
cooling and neutralizing, the mixture is concen- - »
bis- (hydroxymethyl) -pyridine hydrohalide.
3. The process that i comprises lhydrolyzing
dine ‘hydrohalide to form 2-ethyl-3-hydroxy-4,5
trated under reduced pressure, extracted. with
4; The process that comprises heating 2-ethy1
alcohol, dried and further concentrated. The
:3-hydroxy-4,5-bis- (bromomethyl) -pyridine hy
product so obtained is then mixed with about '
drobromide with water to form 2-ethyl-3-hy
50 cc. of hydrobromic acid (48%) and heated to
droxy-4,5-bis- (hydroxymethyl) -pyridine, react
boiling, causing evolution of. methyl bromide
and hydrogen bromide. After concentration fol
lowed by cooling, crystalline‘ 2-ethyl53-hydroxy- I
4,5-bis-(bromomethyl) pyridine hydrobromide is‘ _
obtained. About 1.04 g. of this material are dis;
solved in approximately 100 cc. of water and
ing the latter solution with silver chloride and
recovering 2-‘ethyl-3-hydroXy-4,5-bis-(hydroxy
‘methyD -pyridine hydrochloride.
5. The process that comprises heating 2-ethyl
3-hydroxy-4,5-bis(halomethyl)pyridine
hydro
halide with water to form 2-ethyl-3-hydroxy-4,5
heated at about 95° C. for approximately 25 min
.ibirs(lhydroxymethyl) pyridine hydrohalide. >
20
utes, then the solution is ?ltered, cooled, and
shaken with about 2 g. of silver chloride. The
STANTON A. HARRIS. '
.solution is then ?ltered, concentrated almost to
ANDREW N. WILSON.
dryness at a ‘low temperature, and diluted with
acetone, yielding crystalline 2-ethyl-3-hyroxy
4.»,5-bis-(hydroxymethyl) pyridine hydrochloride,
>melting at about 1914-192.a 0.
25
REFERENCES CITED
‘The following references are of record in the
?le of this patent:
Modi?cations may be made in carrying out the
present invention without departing from ‘the
} Enzyrnologia. VII, 28QCII) 1939, pp. 385-386.
spirit and scope thereof and the invention is to
30.
be limited only by the appended claims.
Документ
Категория
Без категории
Просмотров
0
Размер файла
194 Кб
Теги
1/--страниц
Пожаловаться на содержимое документа