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Патент USA US2594385

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Patented Apr. 29, 1952
Adolph J. Beber, Copley, Ohio, assignor to The
B. F. Goodrich Company, New York, N. Y., a
corporation of New York
N 0 Drawing. ‘Application September 29, 1949,
Serial No. 118,728
2 Claims. (Cl. 260—256.5)
This invention relates to new chemical com
salt with sodium attached to the ester forming
radical in accordance with the equation:
pounds and more speci?cally relates to certain
derivatives of 4-mercapto quinazoline.
The compounds of this invention are deriva
tives of é-mercapto quinazoline having the gen
eric formula
+ XR __.
Examples of esters of this type, prepared in this
and in which the radical R contains only
atoms of carbon, hydrogen and at least one other
element which is oxygen, sulfur or nitrogen in
clude those in which R is a carboxy, hydroxy,
where R is an organic radical containing only
oxy, oxo, thio, thiono, nitro, amino, cyano, or
atoms of carbon, hydrogen and at least one other
element of the group consisting of oxygen, sulfur 15 thiocyano substituted hydrocarbon group, repre
sentative of which are the following:
and nitrogen, and having its connecting valence
(the valence through which the radical R is
é-quinazolyl aminoethyl sul?de
linked to the sulfur atom of the ll-thioéquinazolyl
‘i-quinazolyl nitroethy1 sul?de
radical) on an atom of the group consisting of
4-quinazolyl nitrophenyl sul?des
carbon, sulfur and nitrogen atoms.
20 ‘l-quinazolyl dinitrophenyl sul?des
Typical compounds within this class of deriva
ei-quinazolyl hydroxyphenyl sul?des
tives of é-mercapto quinazoline are grouped
4-quinazolyl carboxyphenyl sul?des
herein in three‘ groups, depending on the nature
4-quinazolyl aminophenyl sul?des
of the atom through which the radical R is con
Alpha-(4-quinazolyl-thio) acetaldehyde
nected to the sulfur of the 4-thio-quinazolyl radi 25 Beta-(4-quinazolyl-thio) propionic acid
ca1,‘as follows:
Alpha-(?l-quinazolyl-thio) acetamide
Beta-(4-quinazolyl-thio) propionitrile
Group I, compounds wherein the R radical has
Alpha-(4-quinazolyl-thio) thiolacetic acid
its connecting valence on carbon.
Alpha- (4-quinazolyl-thio) -beta-merc_apto ethane
Group II, compounds wherein the R radical has
' its connecting valence on sulfur.
The following example illustrates the prepara
Group III, compounds wherein the R radical has
tion of the above-described esters by way of the
its connecting valence on nitrogen.
preparation of the lit-dinitrophenyl ester of
4-mercapto quinazoline. In this example all
In the following description of the invention
parts are by weight.
illustrative compounds within each group and
Example I.——An aqueous solution containing
their method of preparation will be set forth.
4.3 parts of sodium hydroxide in 255 parts of
water was employed to dissolve 16.2 parts of
4-mercapto quinazoline. To this solution of the
Compounds in Group I are further classi?ed,
sodium salt of ll-mercapto quinazoline there was
depending on the nature of the R radical, into
40 added during a period of 25 minutes 20.2 parts of
two types:'
Type A.--C'ompounds of this type are those in
2,4-dinitro-l-chlorobenzene dissolved in 80 parts
of ethyl alcohol. The temperature of the aqueous
which the R radical in the above formula is one
mixture was originally 22° C. but when the mix
which forms esters with acid radicals, that is,
a radical of the kind connected to a functional
45 ture was stirred while the 2,4-dinitro-1-chloro
OH group in an alcohol or phenol.
Such com
pounds are, of course, esters of‘d-inercapto quin
azoline, which is acidic‘. Many such esters are
best prepared by reacting the. sodium salt of
4-mercapto quinazoline ‘with a compound con
benzene was: being added, the temperature in
creased rapidly. By external cooling the tem
perature of the reacting mixture was maintained
at about 35° C. The reaction mixture was stirred
for 2 hours after all the reactants had been com
taining halogen (X) or other radical forming a' 50
‘ _ bined. After this period, the mixture was heated
4-quinazolyl N - cyclopentamethylene - amino
to 60° C. for 10 minutes, cooled to room tempera
ture and ?ltered to recover the yellow precipitate
methyl sul?de
which formed during the reaction. The product
4-quinazolyl N — ethylene - oxy - ethylene-amino
was washed several times with water and dried.
A yield of 90% of a yellow product was recovered
and the product was identi?ed as the 2,4-dinitro
4-quinazolyl N - ethylene - thio-ethylene-amino
phenyl ester of 4-mercapto quinazoline. A por
N ,N’- (quinazolyl-thio-methylene) -para- diamino
methyl sul?de
methyl sul?de
tion of this ester was recrystallized twice from
ethanol and the resulting puri?ed ester had a
The following are examples of the preparation
melting point of 191 to 192° C. By a chemical 10 of representative aminomethyl esters of 4-mer
analysis of the puri?ed ester the percentage com
capto quinazoline. Here also the parts are by
position appearing in the following table was
found, which compares favorably with the calcu
Example II.—4-quinazolyl ortho-tolyl~amino
lated percentage composition also shown in the
methyl sul?de was prepared in the following
following table.
15 manner.
By analysis:
Carbon _________________________ __
Hydrogen _______________________ __
Nitrogen ___- _____________________ __
Sulfur __________________________ __
Oxygen (by difference) __________ __
20 hydrochloride, prepared by adding 49.2 g. of 37%
hydrochloric acid to 53.5 g. of ortho toluidine.
This resulting mixture was stirred and main
tained at room temperature for 2 hours during
which time a yellow precipitate formed. This
yellow precipitate was recovered by ?ltration,
washed with cold water and dried. In this man
ner, 105 g. of the desired product was recovered.
This derivative of 4-mercapto quinazoline was
yellow and without any puri?cation had a, melt
ing point range of 220° to 250° C. This com
pound was found to have the following struc
_________________________ __
Hydrogen _______________________ __
Nitrogen ________________________ __
Sulfur __________________________ __
Oxygen _________________________ __
To a stirred mixture containing 200
ml. of water, 40 g. of a 50% NaOI-I solution, 41
g. of formalin (37% CHzO) and 81 g. of 4-mer
capto quinazoline at 10° C. to 15° C. there was
added 300 ml. of a solution of ortho toluidine
Percentage composition
It is thus established that the compound of this
example has the following structural formula:
Example III.-—An aqueous solution containing
20 g. of sodium hydroxide in 200 ml. of water
was employed to form an aqueous solution of
the sodium salt of 81 g. of 4-merca'pto Quin‘
azoline. To this aqueous solution of the sodium
Accordingly, the compound is named 4-quinazolyl 44 salt of 4-mercapto quinazoline there was added
o,p-dinitrophenyl sul?de or o,D-dinitrophenyl-4
41 g. of formalin (37% CI-IzO) and the result
ing mixture was stirred while an aqueous solu
thio-quinazoline. Other nitroaryl esters of 4
tion of paraphenyl'ene diamine hydrochloride
mercapto quinazoline including the o-m- or p
prepared by the addition of 49.2 g. of hydrochlo
mono-nitrophenyl xesters, the other various
ric acid (37% HCl) ‘to 27 g. of para-phenylene
dinitrophenyl esters, the trinitrophenyl esters,
diamine and diluting to 300 ml. This reaction,’
nitrotolyl and nitronaphthy1 esters, are similar
mixture was stirred for 2 hours at room temper
yellow crystalline compounds which are prepared
ature during which time a precipitate formed.
in an entirely similar manner starting with the
This resulting slurry was ?ltered to recover the
sodium salt of 4-mercapto ‘quinazoline and the
The recovered precipitate was
appropriate chloro and nitro substituted aryl
washed with water and dried. The ‘dried prod
uct identi?ed as N,N'-(quinazolyl-thioemethyl
Esters of this type A also result from the re
ene) para-diamino benzene, weighed 98 g., a
action of 4-merc'apto quinazoline with an amine
yield of 86%, and‘ had a melting point of 247°
and an aldehyde such as formaldehyde (in which
C. to 250° C. This compound is believed to have
case the products are amino-methyl esters),
acetaldehyde or the like. Speci?c examples of 60 the following structural formula:
amino-methyl esters of 4-mercapto quinazoline
(more conveniently named as 4 - quinazolyl
aminomethyl sul?des) are the following:
4-quinalzolyl aminomethyl sul?de
4-q'uinazolyl N-diethylaminomethyl sul?de
4-quinazolyl -N-diisopropyl-aminomethyl sul?de
4-quinazolyl N-paratolyl-aminomethyl sul?de
4-quinazoly1 N-diorthotolyl-aminomethyl sul?de
4-quinazolyl N-anilinomethyl sul?de
4-quinazolyl N-diphenyl-aminomethyl sul?de
4-quinazolyl N-beta-naphthyl-aminomethyl sul
4-quinazolyl N-benzyl-aminomethyl sul?de
4-quinazolyl N-cyclohexyl-aminomethyl sul?de
s /
Type B.-Compounds of this type are those in
which the R. radical, in the above generic for~
70 mula is an acidyl radical, that is, a ‘radical de
rived by removing the OH .group from a carbox
ylic acid, or the SH group from a thio acid or
other compound which reacts as an. acid by
reason of. its containing an acidic —SH group.
75 Compounds of‘ this type include those in which
the radical R is represented by the following
structures in each of which R’ represents hydro
‘l-quinazolyl 4,4,6-trimethyl-thiazinyl—2—sul?de
4-quinazolyl 4,4-dimethyl-oxazolyl-2—sul?de
gen or a hydrocarbon group or a substituted hy
4-quinazo1yl-Xanthogenyl sul?de
4-quinazolyl dimethylcarbamyl sul?de
4-quinazolyl dimethylthiocarbamyl sul?de
drocarbon group (provided of course that the
substituent contains only atoms of the elements
in the class consisting of carbon, hydrogen, oxy
The following is an example of the preparation
gen, sulfur and nitrogen) and R" represents a
bivalent hydrocarbon or substituted hydrocarbon
of type B esters of ll-mercapto quinazoline just
described. The parts herein are also by weight.
Example IV.--The compound ll-quinazolyl
thio-allyl carbonate was prepared by dissolving
46 g. of the anhydrous sodium salt of 4-mer
capto-quinazoline in 300ml. of ethanol. While
this solution was stirred, 31 g. of allyl chloro
carbonate were added slowly causing the temper
16 ature of the reaction mixture to rise from about
30° C. to 40° C. The reacting materials were
then heated to 80° C. for one hour while a yellow
precipitate formed. This resulting slurry was
stirred until it cooled to room temperature. The
20 yellow precipitate was recovered by ?ltration,
washed with ethanol and dried. The resulting
dry yellow solid, the desired product, weighed 28
g. and had a melting point above 320° C. This
compound was found to have the following struc
25 tural formula:
In a like manner similar compounds wherein the
allyl radical is replaced by an alkyl radical such
as methyl, ethyl or butyl or a phenyl radical or
other hydrocarbon radical are also made from
the sodium salt of 4-meroapto quinazoline and
the appropriate chloro-carbonate.
of this group, as hereinbefore
de?ned, are those wherein the R radical in the
above generic formula has its connecting valence
on sulfur. Such compounds include, disul?des,
Compounds of this type are made, in general,
trisul?des and tetrasul?des. The disul?de of 4
by the same reaction set forth in Equation 1
mercapto quinazoline is prepared, for example,
hereinabove, that is by reacting the sodium salt
of 4-mercapto quinazoline with the appropriate 45 by oxidizing the sodium salt of 4-mercapto quin
azoline in an aqueous solution.
acid halide (R—-X) or, in the case of those com
pounds in which R is derived from a compound
Mixed disul?des
can be prepared by oxidizing equimolecular por
tions of the sodium salt of ll-mercapto quin
containing an acidic —SH group, by reacting
azoline and the sodium salt of a R-SH com
the acidic —SH compound with 4-chloro
50 pound in aqueous‘ solution. Tetra sul?des can
quinazoline in accordance with the equation:
be best prepared by reacting the disul?des with,
chlorine to form two moles of sulfuryl chloride
and then reacting the sulfuryl chlorides with
sodium disul?de to form the tetrasul?de and
55 two moles of sodium chloride. This preparation
can be represented by the following equations:
Typical examples of speci?c compounds of this
type include the following: '
4-quinazolyl benzoyl sul?de
4-quinazoly1 thiobenzoyl sul?de.
4-quinazolyl acetyl sul?de
4-quinazo1yl butyryl sul?de
4-quinazolyl phthaloyl sul?de
Bis(4-quinazolyl-thio) ketone
Bis(4-quinazolyl-thio) thione
In the above equation R’ represents the quin
azolyl radical.
4-quinazolyl Z-thiazyl sul?de
ll-quinazolyl z-oxazyl sul?de
Another method commonly employed to pre
pare tetrasul?des is to react the sodium salts of
the mercapto compounds with S2012. Two moles
of sodium chloride are also formed as a by
product in this reaction as indicated in the fol.
70 lowing equation:
4-quinazolyl 2-quinolyl sul?de
a-quinazolyl 2-thiodiazyl sul?de
(R’ is the quinazolyl radical)
a persulfate in the presence, of an. alkali metal
hydroxide or by oxidizing, with chlorine. in the
One method by which the trisul?des: can be
conveniently prepared is by reacting S612 with,
presence of a salt of a weak acid and a strong base
such as sodium carbonate. The formation of the
the sodium salt of ll-mercapto quinazoline- or with
a mixture containing the sodium salt of d-mer
disul?de is believed to take place according to the
capto quinazoline and the sodium salt of the
R—Sl-I compound. The reaction takes place ac
cording to the following equation where R" is
the quinazolyl radical:
following equations:
Examples of di-, tri- and tetrasul?des, which
can be prepared as above described and which
contain the radical R composed only of carbon, 15
hydrogen and at least one other element which
is oxygen, sulfur or nitrogen include the follow
Bis(4-quinazolyl) di-, tri- and tetrasul?des
4-quinazolyl 2-thiazyl di-, tri- and tetrasul?des 20
4-quinazolyl 4,5-dimethyl-thiazyl-2- di-, tri- and
é-quinazolyl 2-benzothiazyl di-,_ tri- and tetra
4-quinazolyl-nitrobenzothiazyl-2 di-, tri- and 25
4-quinazolyl-hydroxybenzothiazyl-2 di-, tri- and
4-quinazolyl ‘ll-methyl - 5 - phenyl-oxazyl-2- di-,
tri- and tetrasul?des
4-quinazolyl benzo-oxazyl-2 di-, tri- and tetra
4-quinazolyl para-nitrophenyl di-, tri- and tetra
é-quinazolyl thiocarbamyl di-, tri- and tetrasul
containing 22.4 parts of sodium persulfate dis
solved in 200 parts of water while the reaction
ll-quinazolyl phenylthiocarbamyl di-, tri- and
mixture was stirred and. the temperature was
maintained at 18-21“ C. During the addition of
the persulfate solution a yellow precipitate was
formed which was recovered, washed. with water
4-quinazolyl N(cyclo-pentamethylene) thiocar
bamyl di-, tri- and tetrasul?des
4 - quinazolyl N (cyclo - ethylene - oxy-ethylene)
and dried. In this manner a 66% yield of the
product, identi?ed as the disul?de of 4.-mercapto
quinazoline having a melting point of 192 to» 195°
C. was recovered. The unoxidized sodium salt of.
‘is-mercapto quinazoline remained in solution.
thiocarbamyl di-, tri- and tetrasul?des
4 - quinazolyl N(cyclo - ethylene - thio-ethylene)
thiocarbamyl di-, tri- and tetrasul?des
4-quinazoly1 cyclohexyl thiocarbamyl di-, tri- and
The percentage compositions of the product‘ and
4-quinazolyl Z-quinolyl di-, tri- and tetrasul?des
4-quinazolyl 2-thiodiazolyl di-. and tetrasul?des
é-quinazolyl 4,4,6-trimethyl thiazinyl-2 di-, tri
that calculated for such a product are given be
low. Accordingly, the compound is named'w
bis(4-quinazolyl) disul?de.
and tetrasul?des
Percentage composition
é-quinazolyl 2-thiazinyl di-, tri- and tetrasul?des
tri- and tetrasul?des
The following are speci?c examples of the
preparation of the disul?de of 4-mercapto
quinazoline wherein the parts are by weight.
Example V.—An aqueous solution containing
4.6 parts of sodium hydroxide and 250 parts of
water was employed to dissolve 16.2 parts of 4
mercapto quinazoline. To this solution there was
added slowly over 45 minutes an aqueous solution
4-quinazolyl dimethylthiocarbamyl di-, tri- and
4 - quinazolyl 4 - ethyl-5-butyl-oxazolinyl-2 di-,
:13 H +2NaCl+H20+CO2
4-quinazolyl isopropyl xanthogen di-, tri- and
4-quinazolyl-para-nitrophenyl disul?de
4-quinazolyl-ortho, para-dinitrophenyl disul?de
The disul?de of Lit-mercapto quinazoline is
readily prepared by oxidation of 4-mercapto
quinazoline but not all methods of oxidation
Total ______________________________ _.
59. 68
59. 60
3. 19
17. 41
19. 94
3. 13
17. 38
19. 89
100. 22.
Example VI .-—An aqueous solution containing
4.6 parts of sodium hydroxide and 105 parts of
which are usually employed in forming disul?des
from mercapto compounds can be employed with 65 water was employed to dissolve 16.2 parts of 4
merca-pto quinazoline. To this solution was
equal success to form this disul?de. For ex
added an aqueous solution containing 5.3 parts of
ample, hypochlorites such as sodium hypochlo
sodium carbonate dissolved in 50 parts of water.
rite, which are commonly employed to oxidize
The resulting aqueous solution was ?ltered to
thiazoles to their corresponding disul?des, are of
no practical use in the oxidation of el-mercapto 70 remove undissolved materials. The ?ltered aque
ous solution was stirred and heated to 55° C. and
quinazoline, for when such oxidizing agent is em
maintained at that temperature for 25 minutes
ployed, there is formed 4-oxy quinazoline instead
while 7.6 parts of chlorine was bubbled through
of the disul?de. I have discovered, however, that
the solution. A yellow precipitate formed‘ as soon
the disul?de can be formed in excellent yield
as the chlorine was added to the solution. The
either by oxidizing 4-mercapto quinazoline with
reaction mixture was stirred one hour after all
the chlorine had been added, was cooled to room
temperature and was ?ltered to recover the di
ous solution of NaOCl were added at such a rate
that the reaction temperature was maintained at
30° C. to 40° C‘. When the stirring was stopped,
two layers formed, an aqueous layer and an oil
sul?de precipitate. A yield of 70% of the disul
?de having a melting point of 192 to 195° C. was
layer. This mixture was filtered to remove a small
amount of ?nely-divided solid material and the
sulfenamide oil layer was taken up wi h ether.
The ether solution was separated from the aque
Compounds of this group, as hereinioei‘ore de
ous phase, dried over sodium sulfate
?ned, are those wherein the R radical in the
above generic formula has its connecting valence 10 char was removed by evaporation. [l5 parts of
residue, the desired sulfenainide, was a dari:
on nitrogen. Such compounds include nitro
hrown free-flowing oil representing a yield of
genous base salts and sulfenamides.
57% were recovered.
The nitrogenous base salts, which are amine
salts, of li—mercapto quinasoline can be prepared
Uses of compounds
in the same manner as any amine salt of an UK
The ‘i-inercapto quinazoline derivatives of this
organic acid, for as herein‘oeiore stated, (‘i-mer
invention are useful for various purposes. They
capto quinazoline is acidic. The sulfenainide de
rivatives of fi-inercapto quinazoline can be pre
pared by oxidizing a mixture of /l-n1ercapto quin
azoline and an amine.
are accelerators for the sulfur vulcanization of
natural and synthetic rubbers, many of them
so being particularly valuable for their “delayed
action” effect,
is more fully disclosed in my
copending application Serial No. 118,729 ?led
September 29, 1949, this use being somewhat sur
The following are typical compounds of this
group Where the connecting valence of the B
group is on nitrogen and the B group contains
prising in View of the fact that organic acceler
ators usually contain the characteristic grouping
only atoms of carbon, hydrogen and at least one
other element which is oxygen, sulfur or nitrogen.
Ammonia salt of ¢i~mercapto quinazoline
Ethylainine salt of ll-inercapto quinazoline
Dlethylamine salt of e~mercapto quinazoline
Unsuhstituted guanidine salt or" é-inercapto quin~
not essentially present
derivatives of é-rner
eapto quinazo-line. Other uses in the rubber and
Diphenyl guanidine sal cr of 4-:nercapto quinazo~
plastics industry for example as modifying in
gredients in the polymegization or" conjugated
Cyclohexylainine salt of Ahmercapto euinaacline
‘dienes, and as vulcanizing agents for vinyl resins
Piperidine salt of fl-inercapto quinazoline
35 are also suggested by the structures herein set
Morpholine salt of Ll-rnercapto quinazoline
forth. In addition, they are valuable economic
azoline '
Ethylene diarnine bisUl-mercapto quinazoline)
poisons and agricultural chemicals, being eiTec
tive as insecticides, fungicides and ba'ctericides.
Those derivatives which possess the 4-quinazolyl~
Phenylene diamine bisUl-mercapto quinazoline) 40 thio radical attached to a carboXy-alkyl radical
or to a radical hydrolyzable thereto, such as beta
Triethylainine salt of 4-rnercapto quinazoline
(e-quinazolyl thio) propionic acid and its amide,
N,N’- (thio-ll-quinazolyl) urea
are useful as plant growth regulants. Other ap
N,l\l’ - (thio-4~quinazolyl) thiourea
plications such as in the synthesis of chemicals
é-quinazolyl isopropyl sulfenarnide
useful as pharmaceuticals and for other purposes
:l-quinazolyl benzyl sulfenamide
will occur to those skilled in the art.
li-quinazolyl dibenzyl sulfenamide
I claim:
Aniline salt of 4~n1ercapto quinazoline
Ll-quinazolyl N-benzyl Zi-methyl sulfenamide
Zl-quinazolyl diphenyl sulfenamide
<i-quinazolyl di~orthotolyl sulfenamide
al-quinazolyl beta-naphthyl sulfenamide
éi-quinazolyl cyclohexyl sulfenamide
ll~quinazolyl N-cyclopentamethylene sulfenamide
‘i-quinazolyl N-cycloethylene-oxy-ethylene sul
1. 4-Quinazoly1 diamyl sulfenamide.
2. A quinazolyl sulfenamide having the struc
e-duinazolyl N~cycloethylene-thio—ethylene sul
‘l-quinazolyl N-cyclotetrarnethylene sulfenamide
Bis(4-quinazolyl) -ethylene disulfenamide
"fris(4-quinazolyl) -diethylen-e trisulienamide
suquinaz'olyl Z-hydroxy-ethyléne sulfenamide
The following example, in which the parts are
by weight, illustrates the preparation of com
pounds of group III where the connecting valence
of the B group is through nitrogen.
Example VII .--4-quinazolyl diamyl sulfenamide
was prepared by ?rst mixing together with stir
ring 40.5 parts of ll-mercapto quinazoline, 500
parts of water and 39.2 parts of diamyl amine.
To this agitated mixture 300 parts of an 8% aque
wherein R1. and R2 are alkyl hydrocarbon radicals
containing 1 to 8 carbon atoms.
The following references are of record in the
?le of this patent:
Hentrich et a1 _____ __ Aug. 13, 1929
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