PROCESS FOR THE PRODUCTION OF MONO- AND BIS-HYDRAZONES OF CARBONOTHIOIC DIHYDRAZIDE

PROCEDE POUR LA PRODUCTION DE MONO- ET DE BIS-HYDRAZONES DE DIHYDRAZIDE CARBONOTHIOIQUE

English Abstract

Mo-3690
CA-058
PROCESS FOR THE PRODUCTION OF MONO- AND
BIS-HYDRAZONES OF CARBONOTHIOIC DIHYDRAZIDE
ABSTRACT OF THE DISCLOSURE
Mono- and bis-thiocarbohydrazones are made by reacting
thiocarbohydrazide or a salt thereof with a carbonyl compound
in the presence of water at a temperature of from about 55 to
about 95°C. A key feature of this process is that no organic
solvent is included in the reaction mixture.
Mo3450

Claims

WHAT IS CLAIMED IS:
1. A process for the production of thiocarbohydrazones in
which no organic solvent is employed comprising reacting
thiocarbohydrazide or a salt thereof and a carbonyl compound in
the presence of water at a temperature of 55-95°C.
2. The process of Claim 1 in which the thiocarbohydrazide
is in the form of an aqueous solution of a mineral acid salt of
thiocarbohydrazide.
3. The process of Claim 2 in which the salt of
thiocarbohydrazide is selected from the group consisting of
thiocarbohydrazide salts of hydrochloric acid
thiocarbohydrazide salts of sulfuric acid, thiocarbohydrazide
salts of phosphoric acid and mixtures thereof.
4. The process of Claim 1 in which an acid is included in
the reaction mixture.
5. The process of Claim 4 in which the acid is a mineral
acid selected from the group consisting of sulfuric acid,
phosphoric acid, hydrochloric acid and mixtures thereof.
6. The process of Claim 5 in which the carbonyl compound
is represented by the formula
<IMG>
in which
R and R' each a represents a hydrogen atom or an
alkyl, alkenyl, aryl, aralkyl, aralkenyl or
heterocyclic group.
7. The process of Claim 6 in which the reaction is
carried out at a temperature of from about 60 to about 70°C.
8. The process of Claim 1 in which the carbonyl compound
is represented by the formula
<IMG>
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in which
R and R' each represents a hydrogen atom or an alkyl,
alkenyl, aryl, aralkyl, aralkenyl or heterocyclic
group.
9. The process of Claim 8 in which
R represents an aryl or aralkyl group and
R' represents hydrogen or an alyl group having
from 1 to 3 carbon atoms.
10. The process of Claim 8 in which the reaction is
carried out at a temperature of from about 60 to about 70°C.
11. The process of Claim 1 in which the carbonyl compound
is salicylaldehyde.
12. The process of Claim 1 in which a pH basic material
is added to the reaction mixture containing the
thiocarbohydrazone in an amount sufficient to neutralize any
acid remaining in the reaction mixture prior to recovery of the
thiocarbohydrazone.
13. The process of Claim 12 in which the thiocarbohy-
drazone is recovered from the reaction mixture and washed with
an organic solvent.
14. The process of Claim 13 in which the organic solvent
wash is selected from the group consisting of methanol,
ethanol, isopropanol, and acetone and mixtures thereof.
15. The process of Claim 1 in which the
thiocarbohydrazide is dissolved in hot water and the carbonyl
compound is an aldehyde.
16. The process of Claim 1 in which approximately two
liters of water are used for each mole of thiocarbohydrazide
included in the reaction mixture.
Mo3690

Description

2082~6~
Mo-3690
CA-058
PROCESS FOR THE PRODUCTION OF MONO- AND
BIS-HYDRAZONES OF CARBONOTHIOIC DIHYDRAZIDE
BACKGROUND OF_THE INVENTION
The present invention relates to a process for the
production of hydrazones of carbonothioic dihydrazide.
The hydrazones of carbonothioic dihydrazide are known to
be effective in inhibiting or preventing the growth of
cellulolytic micro-organisms. One method for producing these
fungicides is disclosed in US Patent 3,734,757. US 3,734,757
teaches that such hydrazones are produced by a condensation
type of reaction between an aldehyde or ketone and
thiocarbohydrazide in the presence of a few drops of glacial
acetic acid and mixture of water and organic solvent. A large
excess (i.e., a molar excess of greater than two) of aldehyde
or ketone is taught to be necessary in this process if an
intractable mixture of mono- and di-substituted derivatives is
to be avoided. The impure mixture of reaction products
obtained by this disclosed process is said to exhibit good
fungicidal properties even though the condensation reaction
product is not isolated.
US Patent 4,058,526 discloses that the condensation of
thiocarbohydrazide with an a~ueous solution of 3,3-dimethyl-
2-oxo-butyric acid to produce 3-mercapto-4-amino-6-tert-
butyl-1,2,4-triazine-5-one or its 3-thione tautomer creates a
waste disposal problem because the waste water from this
process contains organic materials ti.e., organic solvents,
water insoluble unreacted ketone, etc.) which can not be
d;scharged into streams.
It would therefore be advantageous to develop a process
for producing thiocarbohydrazones in which organic solvents
need not be employed.
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SUMMARY OF THE INVENTION
It is an object of the present invention to provide an
improved process for the production of thiocarbohydrazones in
which no organic solvents are employed.
It is another object of the present invention to provide a
process for the production of thiocarbohydrazone in the absence
of an organic solvent without sacrificing product yield.
It is a further object of the present invention to provide
a process for the production of thiocarbohydrazone in which the
reaction temperature is significantly lower than that used in
the prior art processes.
It is also an object of the present invention to provide a
process for the production of substantially pure thiocarbohy-
drazone fungicides from which organic materials such as
solvents need not be removed.
These and other objects which will be apparent to those
skilled in the art are accomplished by reacting thiocarbohy-
drazide or a salt thereof and a carbonyl compound in the
presence of water at a temperature of from about 55 to about
95C. No organic solvent is employed in the process. An acid
may be added to the reaction mixture directly in a preferred
embodiment of the invention. An aqueous solution of a mineral
acid salt of the thiocarbohydrazide may also be employed as the
starting material.
DETAILED DESCRIPTION OF THE INVENTION
lhe present invention relates to an improved process for
the production of thiocarbohydrazones in which thiocarbo-
hydrazide or a salt thereof is reacted with a carbonyl compound
in the presence of water at a temperature of from about
55-95C. A key feature of this process is that no organic
solvent is included in the reaction mixture.
The process of the present invention may be represented by
the following equation:
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H2NN-~-NNH2 + R-C-R'~ N-N-~-N-N=~
II III
in which
R and R' each represent a hydrogen atom or an alkyl,
alkenyl, aryl, aralkyl, aralkenyl or heterocyclic group. R and
R' taken together may also represent a divalent group derived
from a cyclic ketone such as a cyclopentanone or cyclohexanone
in which R and R' together represent tetramethylene or
pentamethylene, respectively. R preferably represents an aryl
or aralkyl group and R' preferably represents hydrogen or an
alkyl group having from 1 to 3 carbon atoms.
Thiocarbohydrazide which is represented by formula I is
known and may be produced in accordance with any of the known
techniques for its production. It has been found that use of
thiocarbohydrazide which has been dissolved in hot water prior
to addition of the carbonyl compound is particularly
advantageous in that more pure monohydrazones are generally
obtained as products.
The carbonyl compounds represented by formula II include
any of the known aromatic or aliphatic aldehydes and ketones.
The nature of the aldehyde or ketone is not critical and a wide
variety of such compounds may be used. For example, aliphatic
aldehydes and ketones, both saturated and unsaturated, aromatic
compounds such as aryl aldehydes, aralkyl aldehydes, diaryl
ketones, alkyl and aryl ketones, heterocyclic aldehydes and
ketones, and aldehydes and ketones containing more than one
aldehydic or ketonic group. Specific examples of such carbonyl
compounds include: formaldehyde t acetaldehyde, valeraldehyde,
hexanal, heptanal, octanal, nonanal, decanal, undecanal,
dodecanal, octadecenal, 9-undecenal, benzaldehyde,
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m-nitrobenzaldehyde, 2,4-dichlorobenzaldehyde, anisaldehyde,
o-chlorobenzaldehyde, p-chlorobenzaldehyde, o-dimethyl-
aminobenzaldehyde, o-hydroxybenzaldehyde, cumaldehyde,
phenylacetaldehyde, cinnamaldehyde, furfural, 2-thiophen-
aldehyde, acetone, methyl ethyl ketone, cyclopentanone,
2-octanone, acetophenone and benzophenone. Preferred carbonyl
compounds include: o-hydroxybenzaldehyde, p-chlorobenzaldehyde,
anisaldehyde, o-chlorobenzaldehyde and phenylacetaldhyde.
The reaction mixture may also optionally include an acid,
preferably a mineral acid. Although acid is not required in
the process of the present invention, if an acid is employed,
it may be used in catalytic quantities (i.e., approximately
1 gm/mole), in an equivalent amount or even in excess. In a
preferred embodiment, mineral acid is added to the thio-
carbohydrazide in water to form the corresponding mineral acid
salt before the carbonyl compound is added to the reaction
vessel.
In carrying out the process of the present invention,
water may be used in any amount which will result in a mixture
that can be stirred. It has been found that use of two liters
of water for each mole of thiocarbohydrazide or thiocarbo-
hydrazide salt generally results in a reaction mixture which is
easily stirred. More water may, of course, be used but such
excess is unnecessary and will increase the amount of water to
be treated upon completion of the reaction. Use of less water
is, of course, also possible particularly where powerful
stirring apparatus are available. However, the use of powerful
stirring equipment will increase the cost of production.
The thiocarbohydrazide and carbonyl compound are generally
reacted in quantities such that one mole of thiocarbohydrazide
is available for every two moles of carbonyl compound.
However, these materials may be employed in quantities such
that the molar ratio of carbonyl compound to thiocarbohydrazide
is from about 1.5:1.0 to about 0.9:1.0, preferably from about
1.0:1.0 to about 1.1:1Ø
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The process of the present invention may be carried out at
temperatures of from about 55 to about 95C, preferably from
about 60 to about 70C and most preferably at a temperature of
about 65C. The reaction time is generally from about 1 to
about 10 hours, preferably from about 3 to 5 hours and most
preferably about 4 hours.
The product thiocarbohydrazone may be readily recovered
from the reaction mixture by any of the known techniques.
Simple filtration of the reaction mixture is just one technique
which is suitable.
Prior to isolation of the product thiocarbohydrazone from
the reaction mixture, it may be advantageous (particularly if
an equivalent amount or an excess of acid was included in the
reaction mixture) to neutralize the reaction mixture.
Once the thiocarbohydrazone has been removed from the
reaction mixture, the purity of the product may be improved by
washing with an organic solvent such as methanol, ethanol,
ispropanol, and acetone. Such washing is, however, optional.
The product of the process of the present invention may be used
directly in the production of fungicide formulations.
In the process of the present invention, the desired
thiocarbohydrazone is generally obtained in a yield of at least
90%, often in yields of from about 97 to about 99%.
Having thus described our invention7 the following
examples are given as being illustrative thereof. All parts
and percentages given in these examples are parts by weight and
percentages by weight, unless otherwise indicated.
EXAMPLES
Example 1
20 ml of water were charged at room temperature to a round
bottomed flask equipped with a mechanical stirrer, thermometer
and condenser. 26.8 gm (0.25 moles) of thiocarbohydrazide were
then added to the flask, followed by the addition of 62.3 gm
~0.5 moles) of salicylaldehyde. The contents of the flask were
Mo3690

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then heated to 80C and maintained at a temperature of from 80
to 82C for two and one-half hours. 400 ml of water were added
to the flask and the contents of the flask were heated to 95C
and mainta;ned at that temperature for approximately 15
minutes. A pale white solid was recovered by filtration. The
solid was washed with water and oven dried. The solid
bis-thiocarbohydrazone thus produced was recovered in a yield
of 89.3% and had an active ingredient content of 95.2%.
Example 2
400 ml of water were charged to a round bottomed flask
equipped with a mechanical stirrer, thermometer and condenser
at ambient temperature. 21.3 ml (0.255 moles) of concentrated
hydrochloric acid and 27.3 gms (0.255 moles) of thiocarbo-
hydrazide were then added to this flask. The contents of the
flask were heated to 60C with stirring to dissolve the
thiocarbohydrazide. After the contents had dissolved, the
temperature was raised to 80C and maintained at that
temperature while 62.3 gms (0.5 moles) of salicylaldehyde were
added. Upon completion of the aldehyde addition, the contents
of the flask were heated at 82-88C for two hours. The hot
contents of the flask were then filtered, rinsed with water and
dried. 78.7 gms of bis-thiocarbohydrazone were recovered
(98.3% yield). HPLC indicated a purity of 100%.
Example 3
500 gms of water were charged to a round bottomed flask
equipped with a mechanical stirrer, thermometer and condenser
at ambient temperature. 0.36 moles of hydrochloric acid and
26.8 gms (0.25 moles) of thiocarbohydrazide were added with
stirring to the flask. The contents of the flask were then
heated to 55C until a clear solution was obtained. 64.8 gms
(Q.52 moles) of salicylaldehyde were then added over a period
Mo3690

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,
of 15 minutes. The temperature of the contents of the flask
were maintained at a temperature of from 55 to 60C during this
addition. Upon completion of the aldehyde addition, the
contents of the flask were maintained at 55C for 4.5 hours.
Sodium hydroxide was added to the contents of the flask until
the pH of the mixture was 5.5. The resultant mixture was then
passed through a filter and the solids recovered were rinsed
with water and dried. 79.4 grams of the bis-thiocarbohydrazone
were recovered (97.6% yield).
Example 4
400 ml of water were charged to a round bottomed flask
equipped with a mechanical stirrer, thermometer and condenser
at ambient temperature. 24.5 gms (0.25 moles) of concentrated
hydrochloric acid and 26.8 gms (0.25 moles) of
thiocarbohydrazide were then added to the flask with stirring.
The contents of the flask were heated with stirring to 60DC
until the mixture was clear. 63.5 gms (0.51 moles) of
salicylaldehyde wer then added to the flask over a period of 15
minutes. The temperature of the contents of the flask were
maintained at 60-65C during the addition of the aldehyde.
Upon completion of the addition of aldehyde, the contents of
the flask were maintained at 60-65C for 7 hours. Upon
completion of this heating, the pH of the reaction mixture was
adjusted to a pH of 6. The solids present in the mixture were
recovered by filtration and dried. 77.7 gms of the desired
bis-thiocarbohydrazone were recovered (99.0% yield). HPLC
indicated a purity of A.l. of 100%.
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Example 5
The procedure of Example 3 was repeated using the same
reactants in the same amounts with the exception that 12.7 gms
(0.125 moles) of sulfuric acid were substituted for the
hydrochloric acid used in Example 3. 78.0 grams of the desired
bis-thiocarbohydrazone (96.3% yield) were recovered. The
product thiocarbohydrazone had a melting point of 201C.
Example 6
The procedure of Example 3 was repeated using the same
reactants in the same amounts with the exception that 14.2 gms
(0.125 moles) of phosphoric acid were substituted for the
hydrochloric acid. 78.0 gms of the desired bis-thio-
carbohydrazone (98.9% yield) were recovered. The product
thiocarbohydrazone had a melting point of 201C.
Although the invention has been described in detail in the
foregoing for the purpose of illustration, it is to be
understood that such detail is solely for that purpose and that
variations can be made therein by those skilled in the art
without departing from the spirit and scope of the invention
except as it may be limited by the claims.
Mo3690