Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
It is known that certain amino aryl compounds can ~:~
be obtained from azoles by ring opening, e.g.
; ~ N / ~ N~2
- According to Houben-Weyl, Methoden der organischen ~.
. 5 Chemie, IX, 3911955] ring opening is possible by means of
.
.~ alkali in the presence of alcohol and the yield can be
:1 improved by addition of a reducing agent, such as sodium
sulphide or zinc dust. Ring opening is also known by means ::
of alkali fusion, without or with addition of a reducing
. lO agent, as described in US Patent Specification 3 103 142. ~;
The present invention relates to an improved process
. . .
for the preparation of amines ~rom azoles by opening an azole ~-
ring in an aqueous alkalLne medium in the presence of an
'~: alcahol and of a reducing agent. The process comprises -.
l 15 treating ia compound of the formula .`
~C Y
N
- 2
:;,i ,
i~ '
~5 ~ 3~ :
wherein X represents a sulphur or a selenium atom, Y
represents an amino group, a lower alkyl group having 1~4
carbon atoms or a mercapto group and ~ represents the atoms
necessary to complete a benzene or naphthalene ring, such
treatment being carried out at a temperature in the range
from 120 to 300C and at a pH greater than 12 in an aqueous ~- ;
diol and in the presence of an alkali metal borohydride or
ammonium borohydride. By means of this treatment the compound
of formula (1) is converted into a compound of formula
. 10
_ ~ / XH
(2)
Z "- NH2
;, :
wherein X and D have the meaningspreviously assigned to them.
Preferably the process may be carried out by
AZ dissolving the compound of formula (1~ in an aqueous diol -
containing a strong alkali to raise the pH of the reaction
medium to a value greater than 12 in the presence of an
alkali metal or ammonium borohydride under reflux conditions,
e.g. at 120 to 180C.
The preferred starting materials are the following ones:
Selenazoles of the formula
Se
(3) ~ Y ;~ `
ZZ `~ N
;~
~ .
~ ~ 3 ~
Z ' ' ',.
,. . - . , - - .. , . ~ , . .. . . . . .. .. . .
~ ~5 ~ ~ 3
wherein Y and D have the meanings already assigned to them,
viz, Y is a substituent different from a hydrogen atom
and D represents the atoms necessary to complete a residue
fused on to the 3,4-position of the azole ring by means of a
benzene or naphthalene ring which may carry substituents;
a 2-amino-arylthiazole;
a 2-amino-arylselenazole or a 2-methyl-arylselenazole. ~:
Preferably aqueous ethylene glycol is used in the
process but any alkyl-substituted or unsubstituted diol such j
. 10 as 1,3-propanediol, 1,2-propanPdiol, 1,4-butanediol, 2,3-
butanediol,monomethoxyethylene glycol and dimethoxyethylene i
glycol which has a boiling point within the temperature range
o~ 120-300C may also conveniently be used. Preferably the
,' , " . '
~ refl~ temperature is 120-180C. . : ~-
~, .,.
:1 : :
,
~ 20.
~,
3 . ~~`
:,1
~, ' ' ' ~'` '
~ 30
i : ~
~ - 4 -
~ ~ S i~ 3 3
The preferred strong alkali is potassium hydroxide
and the preferred borohydride is sodium borohydride. ~
In the process of the p~esent invention, preferably `
2-5 parts of the diol or alkyl substituted diol by weigh~ are
required to dissolve 2 parts by weight of the compound of
formula (1). About 1 part of water to 4 parts of the diol or
alkyl-substituted diol used provides a suitable aqueous diol.
Preferably from 20-25 parts by weight o~ strong alkali per
20 parts of the compound of formula (1) are used. Pre~erably
0.5 to 2.5 parts by weight of borohydride per 20 pares of the
compound of formula (1) are used.
, .; When the compound of formula (2) i9 used as an
intermediate, then in many eases it need not be isolated
but can be converted in the same reaction mixture into the -
desired compound. For instance, the compound of formula (2)
may be conver~ed into an acyl, preferably an acetyl, compound
o~ the formula
5~ , ' , : ' ' .:
X - acyl
(4~ D
~ NH - acyl
,;~ -
j wherein X and D have thè meanings previously assigned to them.
5 ~
.~ . .
.~ ' ,, ' :' ;,. ':
,,, ' ' . , ' , ~ ' . ~ ' ;. ' . . i , ; ~ . . . . '
~ ~5:~ 33
The process of the present invention may be used for
example in a process ~or converting a compound of formula (1),
wherein Y is an amino group, to a compound of formula (1) 9
wherein Y is a mercapto or lower alkyl group, both of which
classes of compound find use as compounds which are added to
photographic emulsions, for example as stabilisers.
Both these classes of compound also find use ias intermediates
in the prepara~ion of optical sensitising dyes,
The compounds of formula (1), wherein Y is an amino
~i 10 group, are relatively easy to synthe~iseand thus the process
. of the nresent invention finds its greatest use in the
conversion of compounds of formula (L) wherein Y is an amino
group, to compounds of formula (1), wherein Y is mercapto or
lower alkyl. However, the process of the present invention
also i~ of great use ~s a step in the reverse process, whereby
compounds of formula (1), wherein Y is methyl or mercapto, may
be ring opened.
When compounds of formula (1), wherein Y i9 NH2, are
to be converted to compounds of formula (1), wherein Y is -CH3,
the first step is to ring-open the ~hiazole or selenazole ring -~
~ by the process of the p~esent invention, the ring opened
'jJ thiazole or selenazole of formula (1) is then reacted in situ
to form an acyl compound of formula (4), which compound may
then be cyclised under reducing conditions to yield the
- 6 -
.' ,
. ~ ' . .
~ S ~ ~ 3 ;
compound of form~tla ~1), wherein Y is a methyl group, as
described in Example 1 herein after set forth.
; After addition of a sufficient quantity of hydrochloric
; S acid, 2-amino-selenols, produc~d in accordance with the
process of the present invention, may be converted in situ
. into 2-mercapto-selenazoles by means of ~arbon disulfide.
:' ,
:' .
.'`, `'
. , .
. .
. .
. , - :.
;, . .
:',. ' ::'
~,
.
. ,
h
~ , ~
,~' ' ' ' ' ' ;.'.,~;
.
3,
- EXAMPLE 1
H3C ~ C-NH~ ~ ~13C ~ SH
H3C N~ H3C NH2
H3C ~ S-OC-CH3 ~~ H3C ~ C -CH
3 ~ NH-OC-CH3 H3C ~ ~ 3
(I) 2-Acetamido-4,5-dimethylphenylthiolacetate
Sodium borohydride (0.92 g) was added to a solution
of potassiumhydroxide (23.4 g) in water (9 ml) and ethane-
1,2-diol ~36 ml). The solution, which was contained in a
250 ml conical flask, was magnetically stirred and treated
with 2-amino-4, 5-dimethylbenzotiazole (18.4 g). The result-
ing mixture was vigorously stirred and heated under reflux
for 4 hours. During the initial period of 0.25 hour of re-
:! fluxing the 2-amino compound completely dissolved in the
medium and a pale straw caloured solution was obtained. Am-
monia was evalved and the solution acquired a temperature of
138C. After refluxing for 1.5 hours, the potassium salt of
the thiol deposited. Water (100 ml) was cautiously added
to the stirred boiling solution and the mixture was heated
I under reflux for 5
'Z ' ~''''
' , '
~ . ~
,' .
~8-
'~
'`
~s~
minutes and diluted wlth more water (250 ml). The solution
was then cooled to 8C and was filtered free from a trace
of suspended solid. The solid was washed with water (50 ml)
and discarded. The combined filtrate was stirred and cooled
to 8C and treated with a mixture of acetic anhydride/acetic
acid (120 ml, 1:1). A colourless crystalline solid deposited
which was collected and washed well with water (300 ml).
The thiolacetate was dried at 50 to a constant weight. -
Yield 21.5 g (88%), m.p. 126-127. ~
. ~
(II) 2,5,6-Trimethylbenzothiazole
;~ A long neck flask containing 2-acetamido-4,5-di~
methylphenyl thiolacetate (6.3 g) was immersed in an oil bath
which was preheated to 230C. The thiol acetate was heated
~ at this temperature for a period of 20 minutes. An air con-
s 15 denser was then fitted to this flask which was heated at 235C
for an additional period of 40 minutes. The flask was re-
moved from the oil bath, cooled to room temperature and the
,;~
~olid was broken up in light petroleum ether (50 ml., b.p. 60-
`~s 80). The mixture was heated under reflux and the insoluble
~20 matter was filtered off and washed with light petroleum (50 ;
1 ml). Evaporation of the filtrate under reduced pressure af-
forded a solid which was dried under vacuo over KOH. Yield
4.5 g (95.5%), m.p. 79-81. ~-
:~ .' ,:
3 _ 9 _
.. . .
~ . . .
EXAMPLE 2
S - [2 - Acetamido - 5,6,7,8 - tetrahydro-l-naphthyl~
thiolacetate
E12 2
H2 ~ 2 H2 ~ H2
H2: ~ 2 ~ S-OC-CH
~ NH-OC-CH3
Sodium borohydride (12.0g) was added to a solution
of potassium hydroxide (306g) in water tll8ml) and ethane-1,2-
diol (47lml). 2-Amino -5,6,7,8- tetrahydronaphtho C2,1~d~ -
thiazole (184g) was added to the solution and the resulting
mixture was vigorously stirred and cautiously heated under
reflux. After stirring and refluxing ~or 5 3/4 hrs, water
(1.31) was added and the solution was heated for a further
period of 5 minutes. More water (3 1) was added to the solu-
tion which was then cooled to 10C and filtered free from a
trace of solid. The clear filtrate was cooled to less than
10C and stirred vigorously whilst a mixture of acetic acid
~' 15 (700ml) and acetic ànydride (700ml) was added slowly~ A
,.. ~ .
colourless crystalline solid deposited which was filtered
after refrigerating the solution overnight. The solid was
~ disintegrated in water (2 1), filtered, washed well with
'1 water and drled to a canstant weight. Yield 214g ~89~) m.p.
' 20 129-140C.
,i .
,~ -- 1 0
`:
~)5~ 3 : ~
EXAMPLE 3
2-Mercapto-5-methylbenzoselenazole
~ ~ C-CH l)KoH/NaBH4 ~ C SH
H C N~ 3 2)HC1 3 H3C ~ N~
3 3)CS2
2,5-Dimethylbenzoselenazole (20 g) was added to a solution
of potassium hydroxide ~24 g) and sodium borohydride (1 y)
in a mixture of water/ethane-1,2-diol (1:4, 50 ml). The
resulting mixture was stirred and heated under reflux for ~
; 5 2.5 hours. The solution was cooled to room temperature and ~ :
treated with ethanol (100 ml)~ Concentrated hydrochloric
acid (30 ml, Sp.Gr. 1.18) was added cautiously (dropwise)
to the stirred ethanolic solution. When the addition of acid
was complete, the stirred solution was treated with carbon
disulphide ~40 ml) and the mixture was heated under reflux
for an additional period of 1 hr. The solvent was then ~`
evaporated under reduced pressure to dryness and the solid
was triturated with water (400 ml), filtered, washed well
' with water and dried. Yield 21.0 g (96~), m.p. 165-167C.
' '~ ' :,."
..
.
' :'
- 1 1 - ;
~ISl0~3
EXAMPLE 4
2-Mercapto-5,6-dimethylbenzoselenazole.
C S ~ 1) KOH/NaBH~ H3C Se~
H3 ~ N 3) CS2 H3 ~C-SH
,,
2,5,6-Trimethylbenzoselenazole (10 g) was added to a solution
of potassium hydroxide (12 g) and sodlum borohydride (0.5 g)
in a mixture of water/ethane-1,2-diol (5 ml:20 mlj.
The resulting mixture was stirred and heated under reflux for
` 2 hrs. The solution was cooled to room temperature and treat-
ed with ethanol (200 ml). The air in the flask was replaced
by nitrogen gas, and the stirred ethanolic solution was treat- `
j ed cautiously with concentrated hydrochloric acid (15 ml, Sp.
,:
~, ~ Gr. 1.18). When addition of the acid was complete, the stirred
solution was treated with carbon disul)phide (30 ml)(the flow
of nitrogen was discontinued). The mixture was refluxed for
~ 15 2 hrs, whereupon a further portion of carbon disulphide (30
$j ml) was added, and the mixture refluxed for a further l hour.
~3
The solvent was evaporated at reduced pressure to dryness and -
the solid was triturated with water (200 ml), filtered, washed
well, and dried.
Yield 9.5 g (88%), m.p. 225-226C.
~ ,' ', .
:', . ,
:~ `',', `
'~' ,: , :,
" : '
i - 12 -
-
', ~
\
:~0~ 3 :i
EXAMPLE 5
. .
2- Mercapto~5-phenylbenzoselenazole ~`
Se~ 1) KOH/NaBH~ ~ S
~ ~ 3 2) ~Cl > ~ ~ C-S~
- 2-Methyl-5-phenylbenzoselenazole (10 g) was added to a so~ lution of potassium hydroxide (12 g) and sodium borohydxide
(0.5 g) in a mixture of water/ethane-1,2-dioI (5ml:20ml). ~ -
The resulting mixture was stirred and heated under reflux -~
for 2 hrs. The solution was cooled to room temperature and
treated with ethanol (200 ml). The air in the flask was re-
~ 10 placed with nitrogen and the stirred ethanolic solution was ~;
; cautiously treated with concentrated hydrochloric acid (15
ml~Sp.Gr. 1.18). When the addition of the acid was complete,
¦ the stirred solution was treated with carbon disulphide (30 ;
ml). (Nitrogen flow was discontinued). The mixture was re-
~j 15 fluxed for 2 hrs. The solution was treated with water (200
?q~ ml) and evaporated under reducQd pressure at 30C to a low
1~ volume (200 ml). The solid was filtered, washed well with
water and dried. Yield llg (98%) m.p.205-206 C.
. ' ,
, : '' ~'~'
,,'i ' `: .
':, ,
1 ' '
: ~,
- 13 - ; ~
~.
EXAMPLE 6
5-Methoxy-2-mercaptobenzoselen~zole
Se 1) KOH/NaBH~ ~ ,,, C-SH
H C O N ~ 2) HCl ~ H3C-O N ~'
. - 3) CS2
5-Methoxy-2-methylbenzoselenazolet20 g) was added to a soluti.on
of potassium hydroxide (24 g) 9 sodium borohydride (1 g) in a
v mixture of waterlethane-1,2~diol (10ml:40ml). The resulting
m$xture was stirred and heated under reflux for 2 hrs. The
- solution wa~ cooled ~to room temperature and treated with ~thanol ~ :
(400 ml). The air in the flask was repl~ced with nitrogen .
and the stirred ethanolic solution was cautiously treated wlth
concentrated hydrochloric aoid (30 ml, Sp,Gr, 1.18). l~hen the
addition wa~ complete, the sollltion was treated with carbon
. disulphide (60 ml) and gently stirred and heated under reflux ;-
for 2 hrs. (~fter addition of carbon d~sulphide.the ~itrogen
~low was di~continued). After ~ hrs~ water (400 ml) was added
to the mixture, which was evaporated unaer reduced pres~ure~
i to yleld a pink solid at a low volume (350 ml), The solid was
filtered off, washed well wi.th water~ and dried.
` ~ield 13,5 g (6~~9 m~p. 170-172C,
, . ~
..
.~ .
- 14 -
.
.~,
1~ 3
EX~MPLE 7
H3C-0 ~ ~ C-CH3 , _ ~ H3C-0 ~ 9~ ~ C SH
1 596-Dimethoxy~2~methylbenzo~elenazole (50 g) was added to a
solution of potassium hydroxide (60 g) and sodium borohydrid~
~4 g) in a mixture of wat~r/ethane-1,2-diol (1:4,125 ml)O The
r~sulting mixture was stirred and heated under reflux for a ~ :.
~eriod of 2 hrs9 until a clear solution was obtained, At this ~ .
stage, ~he air in the flask wa~ displaced with nitrogen and a ~;
~ 10 positive flow of nitrogen was maintained whilst the clear
'~'`! solution was cooled -to room temperature~ Th~ solution was then treated with ethanol (250 ml) stirred and neutralised
cautiously~ with hydrochloric acid (Sp.Gr, 1.18, 75 ml). '~en
~ the addition o~ the acid was complete~ the stirred solution
'~! 1.5 was treated with carbon disulphide (100 ml) ~the flow of
. nitrogen was now discontinued) and the resulting mixture wa~
, .,
~tlrred and heated under reflux for an additional period of
~' 2 hours~ Water (500 ml) was added to the reaction mlxture
~, and the resulting clear solution was ooncentrated under
`!' 20 reduced pressure to eliminate the ~arbon disulphide/ethanol. .
A solid was obtained which was fil-tered off, washed well with
water and driedO
Yield 28 ~, (52%) m.p. 169-171C, :~;
. - 15 -
': ' ~ . . '
~, . . .. . . . .
51 ~ ~ 3 ~ :
EXAMPLE 8
.-
~~ .
Se ~ Se-OC-CH .
`` ~ C-NH2
N ~ ~ NH-OC-CH
Sodium borohydride (1.45 g~ was added to a ~olution of
potassium hydroxide (36.8 g) in water (14 ml) and ethane~1,2- .
diol (56 ml~. The solution was treated with 2-aminobenzoselen-
azole (32 g) and the resulting mixture was vigorously stirred
and heated under reflux for 3~ hr~, The clear sQlution was
diluted with water (154 ml) heated for 5 minutes and diluted
with more water (154 ml,) The solution was then refrigerated ~:
(C10oc~ filtered ~ree from a trace o~ solid which was washed
with water (80 ml). The combined ~iltr~te was cooled to 10C, ~,
;~
vigorously st1rred and cautiously acetylated with a mixture of :~
: acetic acld/acetic anhydyride (1.1, 170 ml)~ The acetamid~
I5 selenol ac~etate Aerivative was filtered of~, washed well with
water and dried to a constant wei,~ht.
Yield 31.9 ~ (~7~o) m.p, 91-93C,
,,, :.. _.- ' ' ;1
I
,.
.
- 16
-'
,~.
