Note: Descriptions are shown in the official language in which they were submitted.
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X-5225 -1-
PROCESS FOR THE PREPARATION OF TRICYCLAZOLE
This invention relates ~o an improved
process of preparing tricyclazole, tricyclazole
being the generic n~me for S-methyl-1,2,4-triazolo-
[3,4-b]~enzothiazole.
U.S. Patent Specification No. 4,064,261
discloses that various triazolobenzoxazoles and
triazolobenzothiazoles r including tricyclazole, are
effec~ive in the control of plant pathogenic organisms,
especially the organism which causes rice bla~t. One
of the methods described in that pa~ent Specification
for the preparation of the tria~olo compounds involves
the reaction of a 2-hydrazinobenzothiazole or benzoxazole
with a carboxylic acid. Tricyclazole is prepared by
the reaction of 2-hydrazino-4-methylbenæothiazole with
formic acid.
Heretofore, a portion of the excess formic
acid employed has been recover~d by distillation.
2~ Isopropyl alcohol wa~ added to the residue from the
distillation to conver~ the remaining ormic acid to
the isopropyL ester and to precipitate the desired
tricyclazole~
The recovery of tricyclazole in this manner
using isopropyl ~lcohol suffer~ from several dis-
advantages. Firstly, only about 43 percent of the
excess formic acid and 75 percent of the isopropyl
alcohol can be recovered and reused. Secondly, the
trict~clazole product is contaminated with 2 1/2 to 3
percent o~ 2,2'-hydrazobis(4-methylbenzothiazole) and
2,2'-azcbls~4-methylbenzothiazole~. These impurities
impart undesirable color to the product.
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The Applicants have now discovered an improve-
ment in the process for the preparation of tricyclazole
from 2-hydrazino-4-methylbenzothiazole and formic acid
which comprises adding an aromatic hydrocarbon solvent
to the reaction mixture at the completion of the
reaction and removing excess formic acid by azeotropic
distillation, followed by crystallization and iso-
lation of tricyclazole from the solvent. The yield
and the purity of tricyclazole are improved and the
consumption o formic acid is reduced by about 40
percent. The two impurities, 2,2'-hydrazobis(4
methylbenzothiazole) and 2,2'-azobis(4-methylbenzothia-
zole), are present in the tricyclazole product in
quantitie~ of less than about 0.4 percent. Waste
streams are also redu~ed.
This invention is an improvement in the
process for the manufacture of tricyclazole by the
reaction of 2-hydrazino 4~methylbenzothiazole with
formi~ acid. The improvement comprises using an
aromatic hydrocarbon solvent rather than isopropyl
alcohol in the workup of the reaction mixture. The
aromatic hydrocarbon solvent is preferably selected
from benzene, toluene and xylene. Xylene is most
preferred. At the completion of the reaction suf-
fici~nt solvent is added to azeotropically remove theexcess formic acid while keeping the tricyclazole
product in solution or in an easily handled slurry.
Upon cooling the mixture after the azeotropic distil-
Lation, the tricyclaæole which precipitates is re-
3Q covered by filtration, centrifugation or similartechnique.
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The aromatic hydrocarbon solvent may be
added upon completion of the reaction and all the
excess formic acid removed as an azeotrope. ~owever,
it is preferred to first remove a portion of the
5 formic acid by distillation, then add the solvent and
remove the remaining formic acid as an azeotrope.
Following the latter procedure, enough formic acid is
left after the initial distillation to maintain a
liquid mixture.
The reaction of 2-hydrazino-4-methylbenzo-
thiazole with formic acid is well-known; however, for
completeness, it will be described below. To effect
the reaction, the reactants are contacted with one
another. The reaction consumes the reactants ln
equimolar amounts, producing tricyclazole and water.
Excess formic acid is used as the reaction medium.
The formic acid used is 80 percent or stronger,
preferably 85 to 90 percent. The reaction goes
forward under a wide range of temperaturss, such as
from about 50 to about 150C. It is convenient and
preferred to conduct the reaction at the reflux
- temperature of the reaction mixture. The tricyclazole
product is then recovered in accordance with the
improved procedure.
The improved process of the invention will be
illustrated by the following non-limitative Examples.
~he xylene utilized was "solvent-grade xylene"
containing 18% of the pa1a-isomer, 18% of the
ortho-isomer, 38-42% of the meta-isomer and 20-24%
3G of the ethyl isomer.
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Example 1
In a 500 ml. 3-neck flask equipped with an
agitator, ~hermometer and condenser were placed 66.5
g~ of 2~hydrazino~4 methylbenzothiazole, 110.7 g. of
98% formic acid and 93.4 g. of recovered formic acid
(78~. The mixture was heated under reflux ak 110C.
for two hours. Formic acid was removed by distillation
to a pot temperature of 130C. The mixture was cooled
to 80C and 200 ml. of toluene was added. The tem-
perature dropped to 45C. bu~ no crystallization
occurred. An azeotrope of formic acid and toluene wasremoved by distillation to a pot temperature of 110C.
The mixture was allowed to cool to room temperature
with crystallization occurriny at abvut 55C. The
slurry became too thick to stir at this temperature
and an additional 50 ml. of toluene was added. The
m:ixture was filtered and the filter cake was washed
with 100 ml. of 12~ sodiurn bicarbonate solution. The
filter cake then was washed with 150 ml. of water
followed by 5G ml. of toluene and was dried in vacuo
; over night at 65C. The yield of tricyclazol~ was
64.6 g. ~92.3%) and assayed 1.98% impurities. The
melting point was 183-185C.
Example 2
In a sno ml. 3~neck flask equipped with an
agitator, thermometer and condenser were placed 66.5 g.
~ o~ 2-hydrazino-4-m~thylbenzothiazole, 110.7 g. of 98
; rormic acid and 93.4 g. of recovered formic acid
(73~). The reaction mixture was heated under reflux
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for 2 hours at 110C. Formic acid was removed by
distillation to a pot temperature of 140C. and 150
ml. of xylene was added. An azeotrope of formic acid
and xylene was removed by distillation to a pot kem-
perature of 141C. Another 150 ml. of xylene was
added and the mixture was cooled to room temperature.
Crystallization occurred at 1~0C. just after the
second 150 ml. of xylene wa~ added. The tricyclazole
product was removed by filtration and was washed with
50 ml. of xylene and dried ln vacuo o~ernight at 65C.
The yield was 59.7 g. (91.1%) and impurities assayed
at 0.56~. The melting point was 181-185C.
E~ample 3
In a 2 1. 3-neck flask equipped with an
agitator, thermome~er and condenser were placed 199.5 g.
of 2-hydrazino-4-methylbenzothiazole and 534 ml. of
8~.7% formic acidO The mixture was heated under
reflux or 2 hours at 109C. During the heating
between 90C and 109C crystals formed and then
dissolved. The 2 hour reflux time began at the time
of solution of the crystals. After refluxing, formic
acid was removed by distillation ~o a pot temperature
of 130C. The first 163 ~1. removed was held apart
from the rest of the distillate. The reaction mixture
was cooled to 100C. and 450 ml. of xylene was added.
The remaining ormic acid was removed azeotropically
over a 3 hour period. The formic acid recovered in
this manner was added to the second portion of formic
acid recovere~ by distillation, giving a total of 363 ml.
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of recovered acid to be recycled. An additional 150
ml. of xylene was added to the residue from the
distillation while main~aining the temperature at
135-140C. The mixture was allowed to cool to room
temperature. Crystalliæation occurred at 123~C.
causing an e~otherm to 125C. The product was re-
covered by filtration and washed with 150 ml. of
xylene. The volume of combined filtrate and washings
was 690 ml. The filter cake was dried in vacuo o~ernigh~
at 85C~ The yield was 180.6 g. (89.5~, corrected for
purity~; impurities assayed 0.47%. The melting point
was 183-188.5C.
The combined filtrate and washings were
distilled to recover 450 ml. of xylene to be recycled
to the next reaction and 125 ml. of xylene to be added
at the end of the azeotropic di~tillation of the next
reaction. At the end of the distillation another 23.3
g. of product with an assay of 53% was recovered.
Example 4
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The proc~dure of Example 3 was repeated
except that the formic acid used was obtained by
adding 98% formic acid to the 363 ml. of formic acid
recovered in Example 3 to give a total volume of 534 ml.
of 87.6~ formic acid. The 450 ml. of xylene added
after distillation of the formic acid was recovered
from Example 3 as was 125 ml. of the 150 ml. of xylene
added at the completion of the a~eotropic distillation.
The yield of tricyclazole was 1~5 g. (91.7%, cor-
3a rected) and impurities assayed 0~6%o The melting
point was 182.5-188C. An additional 20.4 g. of
product with an assay of 51% was recovered from the
mother liquor.
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