The present invention relates to a fungicidal compound of
formula (I). The present invention more particularly relates to a process for
5 preparation of fungicidal sulfenyl phthalimides compound of formula (I)
substantially free from unwanted impurity.
Background and the prior art:
10 Sulfenyl phthalimides developed in the 1950s at Standard Oil are one of the oldest
groups of fungicides and are effective, safe and persistent. Captan (N-
(trichloromethylthio)-3a,4,7,7a-tetrahydrophthalimide, Captafol(N-[1,1,2,2-
tetrachloroethylthiol]-4-cyclohexene-1,2-dicarboximide; and Folpet (N-
[trichloromethylthio] phthalimide, are the three Sulfenyl phthalimides possessing
15 antifungal activity.
Phthalimide and N-substituted phthalimides are an important class of compounds
because they possess important biological activities the identifiable structural
features for their activity are as: hydrophobic aryl ring, a hydrogen bonding domain,
20 an electron-donor group, another distal hydrophobic site.
Some synthetic reactions for preparation of phthalimide moiety includes (1) The
Mathews’ reaction in which a ‘dry’ hydrolysis of nitriles by phthalic acid or amides
by phthalic anhydride takes place and give the corresponding carboxylic acid and
25 phthalimide; (2) reaction of dicarboxylic acids or their corresponding anhydrides
with reagents bearing a reactive amino (–NH2) functional group, through a
nucleophilic attack of amino group to a anhydride moiety to obtain aromatic or
aliphatic cyclic imides and their derivatives; (3) a general synthetic pathway for the
synthesis of imides by direct condensation using cyclic anhydrides or their
30 corresponding dicarboxylic acids and form amide which is a simple affordable
reagent. This approach has the advantage that this specific reagent can also serve as
solvent, especially for aliphatic imides; (4) a preferred method of preparation of
3
sulfenyl phthalimides is reaction of the metal Salt of an imide with perchloromethyl
mercaptan (CISCCl3) in an organic solvent. E.g. synthesis of sulfenyl phthalimide
compound, captan is easily possible by Diels–Alder cycloaddition of maleic
anhydride with butadiene to the tetrahydrophthalic anhydride , which is then
5 converted with ammonia to the tetrahydrophthalimide. Finally, alkylation of the
imide nitrogen atom with perchloromethyl mercaptan delivers Captan.
Folpet and captan are phthalimide based agricultural fungicides that have been in
use for over 60 years. The active moiety of each parent chemical is the
10 trichloromethylthio functional group, SCCl3 which is a toxophore group. The
toxophore group, CCl3—S—, is obtained from trichloromethanesulfenyl chloride,
also known as perchloromethyl mercaptan. Both folpet and captan are degraded to
the reactive substance thiophosgene, along with relatively stable ring structures.
Folpet degrades to phthalimide (PI) and thiophosgene (SCCl2); captan degrades to
15 1,2,3,6-tetrahydrophthalimide (THPI) and thiophosgene. PI and THPI are relatively
stable.
Captan is a non-systemic fungicide used to control diseases of many fruit,
ornamental, and vegetable crops. It is used in agricultural production as well as by
20 the home gardener. Captan can be used to control plant diseases such as black rot,
early and late blight, and downy mildew, among others. Captan works by coming
into contact with a fungus and interrupting a key process in its life cycle. It can be
toxic to many different fungal diseases. Captan is non-systemic, which means it is
not expected to move through plants. It is applied to packing and shipping boxes
25 for fruits and vegetables. Captan is used as a preservative for awnings, draperies
and leather, as a root dip and seed treatment and is incorporated into paints,
wallpaper pastes, plastic and leather goods.
Folpet, a chloroalkylthio compound with broad spectrum protectant fungicide
30 (N-(trichloromethylthio) phth alimide, has been in use for the last several decades.
4
Folpet is predominantly used in agronomic practice along with other industrial
applications today.
During synthesis of sulfenyl phthalimide compounds, manufacturing impurities
5 become important to consider if they are particularly undesirable because of their
toxicological, ecotoxicological or environmental properties. Of the several known
impurities, carbon tetrachloride (a haloalkane impurity) is of great concern from
toxicological point. As per IARC (International Agency for Research on Cancer),
carbon tetrachloride induces hepatic cell proliferation and unscheduled DNA
10 synthesis. Carbon tetrachloride has a mutagenic effect and induces aneuploidy in
several in-vitro systems. Carbon tetrachloride is possibly carcinogenic to humans
(Group 2B). In conclusion, the EU (European Commission) considers carbon
tetrachloride as relevant impurity in captan technical and must not exceed
maximum levels of 0.1 g/kg in the technical material.
15
Carbon tetrachloride is toxic to the central nervous system and liver. It is severely
hepatotoxic, particularly following ingestion. Liver cell damage is apparently
caused by a free radical generated in the process of initial dechlorination. Kidney
injury also occurs. Cardiac arrhythmias, progressing to fibrillation, may follow
20 inhalation of high concentrations of carbon tetrachloride or ingestion of the liquid.
Carbon tetrachloride impairs the NADPH-dependent oxidative enzymes in liver
microsomes by causing irreversible damage to cytochrome P-450. It does not act as
a competitive inhibitor. In the liver, carbon tetrachloride produces elevated levels
of glutamicoxaloacetic transaminase and aldolase (commonly used in following the
25 clinical course of human patients poisoned by the compound). Centrolobular
necrosis of the liver is the lesion most characteristic of poisoning by carbon
tetrachloride. The necrosis progresses cell by cell. Electron microscopy reveals
vesiculation of the rough endoplasmic reticulum, clumps of tangled, smooth
membranes, and vacuolization of the Golgi apparatus. It also reveals loss of
30 polysomes and accumulation of fat. Definite renal tubular lesion, including tubular
necrosis and deposition of calcium, have been observed regularly. Mitochondria
5
and not endoplasmic reticulum appear to be the primary subcellular site of carbon
tetrachloride toxicity in the kidney.
Carbon tetrachloride also contributes to the destruction of the Earth's ozone layer,
5 which protects us from harmful ultraviolet radiation. Carbon tetrachloride (CCl4) is
an ozone‐depleting substance, accounting for about 10% of the chlorine in the
troposphere. Under the terms of the Montreal Protocol, its production for dispersive
uses was banned under the Montreal Protocol since 2010.
10 Therefore, it is important to minimize the level of carbon tetrachloride impurity as
much as possible while synthesizing sulfenyl phthalimides to avoid its exposure to
agricultural workers handling the captan technical as well as to avoid environmental
hazards.
15 US2553770 discloses synthesis of sulfenyl phthalimide compounds. The patent
discloses reaction of sulfenyl phthalimide compound in dioxane solvent which is
then followed by purification through crystallization in carbon tetrachloride as
solvent.
20 US2553771 discloses synthesis of sulfenyl phthalimide compounds which
comprises dissolving an imide of a dicarboxylic acid in an aqueous alkaline solution
of an alkali metal compound and reacting the resulting product with
perchloromethyl mercaptan. Addition of carbon tetrachloride in both of these
patents further contributes to increase the level of carbon tetrachloride impurity in
25 finally synthesized sulfenyl phthalimides.
US2553776 discloses synthesis of captan in which water is used as a solvent in the
final step. Also, effect of addition of sodium chloride and potassium chloride to
improve the yield of the final product is also disclosed in the said patent. However,
30 patent does not disclose anything about impurity as well as its amount in the final
product.
6
US2713058 discloses an improved method of synthesis of Ntrichloromethylthioimides comprising carrying out the reaction of perchloromethyl
mercaptan with the alkali metal imide product dissolved in the aqueous media in
the presence of a water-immiscible, saturated organic solvent for the
5 perchloromethyl mercaptan. The latter is preferably added to the reaction system
dissolved in the organic solvent (saturated C5-C9 hydrocarbon) and results in the
obtaining of products of substantially increased purity. Although, the Ntrichloromethylthioimides obtained according to the invention has more than 95%
purity but this patent does not disclose anything about haloalkane impurity and its
10 amount handled during synthesis of N-trichloromethylthioimides.
US3314969 discloses a method for preparing N-trichloromethylthioimide
compounds comprises isolating N-polyhaloethylthio compound from the aforesaid
reaction mixture as a polar solvent dispersion; contacting said dispersion with an
15 aromatic hydrocarbon solvent of from 6 to 10 carbons at a temperature in the range
of about 50 to 100 C. for a time sufficient to dissolve substantially all of the Npolyhaloethylthiocompound; separating the polar solvent phase from the aromatic
hydrocarbon solvent phase; cooling the aromatic hydrocarbon phase and isolating
therefrom the purified N-poly-haloethylthio compound. US3314969 uses alkali
20 metal salts in the aqueous phase and added the trichloromethylsulfenyl chloride
diluted in an aliphatic hydrocarbon solvent to the aqueous solution of the imide.
The prior art does not disclose how does carbon tetrachloride been handled in the
final product.
25 Although, attempts have been made to obtain substantially pure
sulfenyl phthalimides but it is still required to develop a simple, efficient and cost
effective process to obtain sulfenyl phthalimides which has below minimum
acceptable limit of haloalkane impurity especially, carbon tetrachloride impurity.
30
7
Objectives of the Invention
An objective of the present invention is to develop fungicidal sulfenyl phthalimide
compounds substantially free from unwanted haloalkane impurities.
5 An objective of the present invention is to develop sulfenyl compound substantially
free from haloalkane impurities.
Yet another objective of the present invention is to develop fungicidal
sulfenyl phthalimide compounds substantially free from carbon tetrachloride using
10 aromatic hydrocarbon that minimizes haloalkane impurities in the fungicidal
sulfenyl phthalimide compounds.
Another object of the invention is to provide a simple process for the preparation of
sulfenyl phthalimide compounds in high yield and high purity. The process is
15 simple, easy and convenient to carry out, economical and efficient.
Still another objective of the present invention is to provide a process of preparing
fungicidal sulfenyl phthalimide compounds substantially free from haloalkane
impurities wherein said process is efficient, simple and cost effective.
20
Yet another objective of the present invention is to develop a method wherein a
high yield of fungicidal sulfenyl phthalimide compounds is obtained.
Summary of the Invention
25
In an aspect the present invention relates to prepare a fungicidal sulfenyl
phthalimide compound of formula (I) wherein said compound of formula (I) is
substantially free from unwanted haloalkane impurities.
30
In another aspect the present invention relates to prepare a fungicidal sulfenyl
phthalimide compound of formula (I)
8
(I)
5
wherein K together with the two contiguous linking carbon atoms, forms a fused
6-membered aromatic ring a or a fused cyclohexene ring, wherein said compound
of formula (I) is substantially free from haloalkane impurities.
10 In another aspect the present invention provides a process for preparation of
compound of formula (I) wherein K together with the two contiguous linking
carbon atoms, forms a fused cyclohexene ring (that is substantially free from
haloalkane impurities wherein said compound of formula (I) is 3a,4,7,7aTetrahydro-N-(trichloromethanesulphenyl)phthalimide.
15
In another aspect the present invention provides a process for preparation of
compound of formula (I) wherein K together with the two contiguous linking
carbon atoms, forms a fused aromatic ring that is substantially free from haloalkane
impurities wherein said compound of formula (I) is N20 (Trichloromethanesulphenyl)phthalimide.
In another aspect the present invention provides a process for preparation of
compound of formula (II) substantially free from haloalkane impurities used for
preparation for compound of formula (I).
25
(II)
In another aspect of the present invention, a process for the synthesis of fungicidal
sulfenyl phthalimide compound of formula (I) which is substantially free from
30 haloalkane impurities comprising :
(a) reacting an organosulphur compound with chlorine to form a sulfenyl
compound of formula (II);

N
O
O
S CCl3
K
Perchloromethyl mercaptan
S
Cl Cl
Cl Cl
CS2 + Cl2
gas
HCl + water
Formula Weight = 76.0 Formula Weight = 185.88
Perchloromethyl mercaptan
(PCMM)
carbon disulfide
Step-01
9
(b) converting said sulfenyl compound of formula (II) to a fungicidal
5 sulfenyl phthalimide compound of formula (I) substantially free from
haloalkane impurities.
In another aspect of the present invention, the process for the synthesis of fungicidal
sulfenyl phthalimide compound of formula (I) comprising
(a) reacting an organosulphur compound with chlorine to form sulfenyl
10 compound;
(b) isolating pure sulfenyl compound by treating sulfenyl compound with
aromatic hydrocarbon to remove haloalkane impurity;
(c) reacting sulfenyl compound of formula (II) with phthalimide or
phthalimide derivative to obtain pure sulfenyl phthalimide compound of
15 formula (I);
In another aspect of the present invention, a process for the synthesis of 3a,4,7,7aTetrahydro-N-(trichloromethanesulphenyl)phthalimide compound of formula (I)
which is substantially free from haloalkane impurity, comprises the steps of:
(a) reacting organosulphur compound with chlorine to form sulfenyl
20 compound;
(b) treating sulfenyl compound of step (a) with aromatic hydrocarbon to
remove haloalkane impurity to obtain pure sulfenyl compound of
formula (II);
(c) reacting sulfenyl compound of formula (II) with
25 tetrahydropthalimide to obtain pure 3a,4,7,7a-Tetrahydro-N-
(trichloromethanesulphenyl)phthalimide compound of formula (I);
In another aspect of the present invention, a process for the synthesis of
N-(Trichloromethanesulphenyl)phthalimide compound of formula (I) which is
substantially free from haloalkane impurity wherein, said process comprises steps
30 of: Perchloromethyl mercaptan
S
Cl Cl
Cl Cl
CS2 + Cl2
gas
HCl + water
Formula Weight = 76.0 Formula Weight = 185.88
Perchloromethyl mercaptan
(PCMM)
carbon disulfide
Step-01

Formula II
10
(a) reacting organosulphur compound with chlorine to form sulfenyl
compound;
(b) treating sulfenyl compound of step (a) with aromatic hydrocarbon to
remove haloalkane impurity to obtain pure sulfenyl compound of
5 formula (II);
(c) reacting sulfenyl compound of formula (II) in an aromatic hydrocarbon
with phthalimide to obtain pure N-
(Trichloromethanesulphenyl)phthalimide compound of formula (I);
10 In an aspect of the present invention, the process for the synthesis of sulfenyl
compound of formula (II) which is substantially free from haloalkane impurity
comprises the steps of:
(a) reacting an organosulphur compound with chlorine to form sulfenyl
compound;
15 (b) treating sulfenyl compound of step (a) with aromatic hydrocarbon to
remove haloalkane impurity and obtaining pure sulfenyl compound of
formula (II) which is substantially free from haloalkane impurities.
In another aspect of the present invention, a process for the synthesis of fungicidal
sulfenyl phthalimide compound of formula (I) which is substantially free from
20 haloalkane impurities wherein, said process comprises: reacting sulfenyl compound
of formula (II) in an aromatic hydrocarbon with pthalimide or phthalimde derivative
compound and obtaining fungicidal sulfenyl phthalimide compound of formula (I).
Detailed Description of the invention:
25 While several embodiments of the present invention have been described and
illustrated herein, those of ordinary skill in the art will readily envision a variety of
other means and/or structures for performing the functions and/or obtaining the
results and/or one or more of the advantages described herein, and each of such
variations and/or modifications is deemed to be within the scope of the present
30 invention.
11
Surprisingly, inventor of the present invention found that a fungicidal
sulfenyl phthalimide compounds for formula (I), can be obtained in the
substantially pure form with negligible haloalkane impurities, if sulfenyl compound
5 is made by means of chlorination of carbon disulfide, followed by treatment of the
obtained crude sulfenyl compound with aromatic hydrocarbons; and reacting
sulfenyl compound with phthalimide or phthalimide derivative and further treating
with aromatic hydrocarbons to obtain substantially pure sulfenyl phthalimide
compound.
10
Aromatic hydrocarbon treatment used during synthesis of both, sulfenyl compound
and sulfenyl phthalimide compounds helps in reducing haloalkane impurities which
ultimately leads to substantially pure sulfenyl phthalimide compounds.
Advantageously the present invention has achieved improvements in the production
15 of sulfenyl phthalimide compounds and derivative compounds, for example captan,
and folpet via the use of aromatic hydrocarbons which are believed to minimize the
formation of the undesirable haloalkane impurities.
Broadly, present invention contemplates a fungicidal sulfenyl phthalimide
compound substantially pure from haloalkane impurities and process of preparing
20 fungicidal sulfenyl phthalimide compound substantially pure from haloalkane
impurities using aromatic hydrocarbons. The process contemplated by this
invention is further explained by the following reaction scheme.
Step I:
25
CS2 + Cl2
30
Perchloromethyl mercaptan
S
Cl Cl
Cl Cl
CS2 + Cl2
gas
HCl + water
Formula Weight = 76.0 Formula Weight = 185.88
Perchloromethyl mercaptan
(PCMM)
carbon disulfide
Step-01
Acid
Aromatic
hydrocarbon
Formula II
12
Step II:

NH
O
O
K

5
In accordance with the present invention, fungicidal sulfenyl phthalimide
compound of formula (I) describe some of the preferred compounds wherein said
compound of formula (I) represented as the structure given below is substantially
10 free from haloalkane impurities is,
15
(I)
wherein K together with the two contiguous linking carbon atoms, forms a fused
6-membered aromatic ring a or a fused cyclohexene ring.
20
In an embodiment the present invention provides a compound of formula I wherein
K together with the two contiguous linking carbon atoms, forms a fused
cyclohexene ring (that is substantially free from haloalkane impurity and process
for preparation thereof wherein said compound of formula (I) 3a,4,7,7a-Tetrahydro25 N-(trichloromethanesulphenyl)phthalimide and is represented as below:
30
In an embodiment the present invention provides a compound of formula I wherein
K together with the two contiguous linking carbon atoms, forms a fused aromatic
Perchloromethyl mercaptan
S
Cl Cl
Cl Cl
CS2 + Cl2
gas
HCl + water
Formula Weight = 76.0 Formula Weight = 185.88
Perchloromethyl mercaptan
(PCMM)
carbon disulfide
Step-01
Base
Aromatic
hydrocarbon
Formula I
+
N
O
O
S CCl3
K
13
ring that is substantially free from haloalkane impurities and process for preparation
thereof wherein said compound of formula (I) is N-
(Trichloromethanesulphenyl)phthalimide represented as below:
5
According to an embodiment of the present invention, there is provided a compound
10 of formula (II) substantially free from haloalkane impurity and process for
preparation thereof.
15
(II)
In accordance with the present invention, the compound of formula (II) is also
known as Trichloromethane sulfenyl chloride or Perchloronemethylmercaptan
20 (PCMM).
In accordance with the present invention, a fungicidal sulfenyl phthalimide
compound of formula (I) is substantially free from haloalkane impurities.
25 In accordance with the present invention, a fungicidal sulfenyl phthalimide
compound of formula (I) substantially free from haloalkane impurities refers to a
compound of formula (I) with less than 0.05%, preferably less than 0.01% of
haloalkane impurity ( by Gas Chromatography).
30 In accordance with the present invention, a sulfenyl compound of formula (II) is
substantially free from haloalkane impurities.
Perchloromethyl mercaptan
S
Cl Cl
Cl Cl
CS2 + Cl
2
gas
HCl + water
Formula Weight = 76.0 Formula Weight = 185.88
Perchloromethyl mercaptan
(PCMM)
carbon disulfide
Step-01
14
In accordance with the present invention, a sulfenyl compound of formula (II)
substantially free from haloalkane impurities refers to compound of formula (II)
with less than 0.10, preferably less than 0.08% of haloalkane impurities ( by Gas
Chromatography).
5
According to an embodiment of the present invention, the haloalkane impurities
refers to unwanted impurities belong to the group comprising of carbon
tetrachloride and dichloro(chlorosulfanyl)methanesulfonyl chloride or mixture
thereof that are generated during the process of synthesis of sulfenyl compound or
10 sulfenyl phthalimide compounds.
Typically, according to a preferred embodiment of the present invention, the
haloalkane impurity is carbon tetrachloride.
15 According to an embodiment of the present invention, the haloalkane impurity
present in sulfenyl phthalimide may be any impurities including reaction byproducts, intermediates, starting materials, and solvents.
According to an embodiment of the present invention, haloalkane impurities are
20 capable of being removed azeotropically, such as by vacuum distillation, heat, or
low-pressure evaporation.
According to an embodiment of the present invention, haloalkane impurity is
preferably removed by distillation.
25
According to an embodiment of the present invention, a process for the synthesis
of fungicidal sulfenyl phthalimide compound of formula (I) which is substantially
free from haloalkane impurities wherein, said process comprises steps of:
(a) reacting an organosulphur compound with chlorine to form sulfenyl
30 compound and treating sulfenyl compound with aromatic hydrocarbon
15
to remove haloalkane impurities to obtain pure sulfenyl compound of
formula (II) and
(b) reacting sulfenyl compound of formula (II) in an aromatic hydrocarbon
with phthalimide or pthalimide derivatives to obtain pure sulfenyl
5 phthalimide compound of formula (I).
In an embodiment, step (a) is carried out in presence of aqueous acidic medium and
sulfenyl compound is further treated with aromatic hydrocarbon solvent to obtain
pure sulfenyl compound of formula (II) substantially free from haloalkane
impurities.
10
In an embodiment, step b) is carried out in presence of in an aqueous alkaline
medium and sulfenyl phthalimide compound is further treated with aromatic
hydrocarbon to obtain pure sulfenyl phthalimide compound (I) substantially free
from haloalkane impurities.
15
According to an embodiment of the present invention, a process for the synthesis
of fungicidal sulfenyl phthalimide compound of formula (I) which is substantially
free from haloalkane impurity wherein, said process comprises steps of:
(a) reacting organosulphur compound with chlorine to obtain crude sulfenyl
20 compound;
(b) treating crude sulfenyl compound of step (a) with aromatic hydrocarbon
to remove haloalkane impurity and obtaining sulfenyl compound of
formula (II);
(c) reacting sulfenyl compound of formula (II) with phthalimide or
25 pthalimide derivatives to obtain sulfenyl phthalimide compound of
formula (I);
According to an embodiment of the present invention, a process for the synthesis
of 3a,4,7,7a-Tetrahydro-N-(trichloromethanesulphenyl)phthalimide compound of
formula (I) which is substantially free from haloalkane impurities wherein, said
30 process comprises steps of:
16
(a)reacting organosulphur compound with chlorine to obtain crude sulfenyl
compound;
(b)treating crude sulfenyl compound of step (a) with aromatic hydrocarbon
to remove haloalkane impurities and obtaining sulfenyl compound of
5 formula (II);
(c)reacting sulfenyl compound of formula (II) in an aromatic hydrocarbon
with tetrahydropthalimide to obtain 3a,4,7,7a-Tetrahydro-N-
(trichloromethanesulphenyl)phthalimide compound of formula (I).
In step a) the organosulphur compound is carbon disulfide and sulfenyl compound
10 is perchloromethyl mercaptan. Typically, the step a) is carried out at 5 to 10°C.
After completion of the reaction of step a) the reaction mass is treated aromatic
hydrocarbon solvent. The aromatic hydrocarbon solvent used is selected from the
group comprising toluene, chlorobenzene, ethyl benzene, propyl benzene, xylene
and the like. The solution thus obtained is then subjected to distillation to remove
15 the unwanted impurities and isolating pure sulfenyl compound which can be
directly used for preparation of sulfenyl phthalimide compound of formula (I)
without further purification.
In step c) pure sulfenyl compound as obtained in step b) is reacted with
20 tetrahydropthalimide in aqueous basic medium. Typically, the reaction is performed
at low temperature preferably at 0 to 10°C, more preferably at 0 to 5°C for 1 to 5
hours preferably for about 1 to 2 hours. The reaction mass is then charged with
aromatic hydrocarbon solvent and the mixture is heated to temperature in the range
from 50 to 100°C, preferably at 70-80°C and pure sulfenyl phthalimide compound
25 is isolated from the mixture having high purity and high yield as well as reduced
unwanted haloalkene impurities preferably to below 0.01%.
According to an embodiment of the present invention, a process for the synthesis
of N-(Trichloromethanesulphenyl)phthalimide compound of formula (I) which is
30 substantially free from haloalkane impurities wherein, said process comprises steps
of:
17
(a) reacting organosulphur compound with chlorine to form sulfenyl
compound;
(b) treating sulfenyl compound of step (a) with aromatic hydrocarbon to
remove haloalkane impurities and obtaining sulfenyl compound of
5 formula (II);
(c) reacting sulfenyl compound of formula (II) with phthalimide to
obtain N-(Trichloromethanesulphenyl)phthalimide compound of
formula (I).
10 According to an embodiment of the present invention, a process for the synthesis
of sulfenyl compound of formula (II) which is substantially free from haloalkane
impurities wherein, said process comprises steps of:
(a) reacting organosulphur compound with chlorine to obtain crude
sulfenyl compound;
15 (b) treating crude sulfenyl compound of step (a) with aromatic
hydrocarbon to remove haloalkane impurities and obtaining sulfenyl
compound of formula (II) which is substantially free from
haloalkane impurities.
In another aspect of the present invention, a process for the synthesis of fungicidal
20 sulfenyl phthalimide compound of formula (I) which is substantially free from
haloalkane impurities wherein, said process comprises:
reacting sulfenyl compound of formula (II) with pthalimide or phthalimide
derivative and obtaining fungicidal sulfenyl phthalimide compound of
formula (I);
25
According to an embodiment of the present invention, a process for the synthesis
of 3a,4,7,7a-Tetrahydro-N-(trichloromethanesulphenyl)phthalimide compound of
formula (I) which is substantially free from haloalkane impurities wherein, said
process comprises:
18
reacting sulfenyl compound of formula (II) obtained according to the present
process with tetrahydropthalimide and obtaining pure 3a,4,7,7a-Tetrahydro-N-
(trichloromethanesulphenyl)phthalimide compound of formula (II) substantially
free from haloalkane impurities.
5 According to an embodiment of the present invention, organosulphur compound is
selected from the group comprising of carbon disulfide, carbonyl sulphide,
thiophosgene and the like.
According to preferred embodiment of the present invention, organosulphur
10 compound carbon disulfide.
According to an embodiment of the present invention, acid medium utilized in step
(a) to form sulfenyl compound of formula (II) is selected from the group comprising
of hydrochloric acid (HCl), phosphoric acid, sulfuric acid.
15
According to preferred embodiment of the present invention, acid medium utilized
in step (a) to form sulfenyl compound of formula (II) is hydrochloric acid (HCl).
According to an embodiment of the present invention, alkaline medium utilized in
20 step (b) to form sulfenyl phthalimide compound of formula (I) is selected from the
group comprising of sodium hydroxide (NaOH), potassium hydroxide (KOH),
Lithium hydroxide (LiOH), potassium carbonate (K2CO3) and the like.
According to preferred embodiment of the present invention, alkaline medium
25 utilized in step (b) to form sulfenyl phthalimide compound of formula (I) is sodium
hydroxide (NaOH).
According to an embodiment of the present invention, aromatic hydrocarbon used
for synthesis of sulfenyl phthalimide compound of formula (I) and sulfenyl
30 compound of formula (II) are selected from the group comprising of toluene,
chlorobenzene, ethyl benzene, propyl benzene, xylene and the like.
19
According to preferred embodiment of the present invention, aromatic hydrocarbon
used for synthesis of sulfenyl phthalimide compound of formula (I) and sulfenyl
compound of formula (II) is toluene.
5 Accordingly, a fungicidal sulfenyl phthalimide compound of formula (I), obtained
by the present process as described above is substantially free from haloalkane
impurities.
Preferably, 3a,4,7,7a-Tetrahydro-N- (trichloromethanesulphenyl)phthalimide
obtained by the present process is substantially free from haloalkane impurities.
10
Preferably, N-(Trichloromethanesulphenyl) phthalimide obtained by the present
process is substantially free from haloalkane impurities.
In an embodiment, the process according to the present invention provides
15 fungicidal sulfenyl phthalimide having particle size distribution D10 of less than
about 23.101 microns.
In an embodiment, the process according to the present invention provides
fungicidal sulfenyl phthalimide having particle size distribution D50 of less than
about 72.223 microns.
20
In an embodiment, the process according to the present invention provides
fungicidal sulfenyl phthalimide having particle size distribution D90 of less than
about 172.728 microns.
25 According to the invention the compound of formula (1) is obtained in high yield
and has high purity of more than 98.5 %. The present process is simple, easy and
convenient to carry out, efficient, economical and also industrially and
commercially viable.
According to an embodiment of the present invention, fungicidal sulfenyl
30 phthalimide compound may be used in any kind of solid or liquid formulation meant
for agrochemical application along with other optional components including but
20
not limited to surfactants, dispersing agents; wetting agents; antifoaming agents;
antimicrobial agents; antioxidants; buffers; dyes; perfumes; stabilizing agents; and
water-soluble salts.
5 According to an embodiment of the present invention, fungicidal sulfenyl
phthalimide compound may also be mixed with other agrochemically acceptable
ingredients, for example fertilizers such as ammonium nitrate, urea, potash, and
superphosphate; phytotoxicants and plant growth regulators; safeners; and
pesticides.
10
According to an embodiment present invention provides a fungicide composition
comprising a fungicidal sulfenyl phthalimide compound of formula (I) substantially
free from haloalkane impurities prepared according to present process. In another
embodiment the present invention provides a method of treating fungal infection
15 by applying to the locus a fungicidal sulfenyl phthalimide compound of formula (I)
substantially free from haloalkane impurities prepared according to present process.
It will be apparent to those skilled in the art that various modifications and
variations can be made in the present invention without departing from the scope
20 or spirit of the invention. Other embodiments of the invention will be apparent to
those skilled in the art from consideration of the specification and practice of the
invention disclosed herein. It is intended that the specification and examples be
considered as exemplary only, with a true scope. The process of preparing sulfenyl
phthalimide compound is illustrated in the following examples:
25
EXAMPLES
Example 1:
Synthesis of 3a,4,7,7a-Tetrahydro-N-(trichloromethanesulphenyl)
30 phthalimide
21
Step 1: In 1664g water, 974g (30%) aqueous HCl solution and 380g carbon
disulfide was charged at 5-10°C and chlorine gas was purged for 22-24 hrs at same
temperature. After completion of reaction, layers were separated, organic mass was
collected and toluene (210 gm) was added and further organic layer was washed
5 two times with 250 gm water. 905 g crude Perchloromethyl Mercaptan (PCMM)
toluene solution was obtained. Distillation was performed of crude PCMM toluene
solution on 3 feet packed column to remove low boiler and haloalkane impurity,
carbon tetrachloride (CTC) along with toluene under vacuum. The PCMM toluene
solution thus obtained was further taken for step 2. Final sulfenyl compound (the
10 PCMM) specification: Residual PCMM: (778.0 g). Yield: 77.0%, Purity: 92.61%
with CTC-0.07 % (by GC).
Step 2: In 400 g water, 44.60 g (48%) NaOH solution was charged and then cooled
to 10-15°C. To the above solution, 81.38 g tetrahydrophthalimide was slowly added
15 in 10-15 min span and further stirred for 45 min at same temperature clear solution
was observed and then cooled to 0-2°C to obtain reaction mass. Separately, 100.4
g PCMM solution obtained in step 1 was added to above reaction mass during
addition precipitation was observed and stirred for 2.0 hrs at same temperature. In
work up, toluene (323 g) was charged and reaction mass was heated to 75-80°C
20 under stirring for 30 min and cooled to 20-25°C, filtered and the washed with
toluene (85 g) and hot water (98 g) two times to finally give an isolated dry solid of
133.4 g. Final sulfenyl phthalimide compound specification: Yield: 88.78%, Purity:
98.70 % with 0.0092 % CTC.
25 Example 2:
Synthesis of 3a,4,7,7a-Tetrahydro-N-(trichloromethanesulphenyl)
phthalimide
Step-I: In 323.6 g water, 188.8g (30%) aqueous HCl solution and carbon disulfide
30 (73.6 g) was charged at 5-10°C and chlorine gas was purged for 22-24 hrs at the
same temperature. After completion of reaction, layers were separated.
22
chlorobenzene (48.4 gm) was added to organic mass and washed two times with
48.4 gm water. 192.0g crude Perchloromethyl Mercaptan (PCMM) chlorobenzene
solution was obtained. Distillation was performed of crude PCMM chlorobenzene
solution on 3 feet packed column to remove low boiler and haloalkane impurity,
5 carbon tetrachloride (CCl4) along with chlorobenzene under vacuum. The PCMM
chlorobenzene solution thus obtained was further taken for step 2. Final sulfenyl
compound (the PCMM) specification: Residual PCMM: (147.2 g). Yield: 72.0 %,
Purity: 88.10 % with, CTC-0.06%.
10 Step 2: In 302.4 g water, 33.72g (48%) NaOH solution was charged and then
cooled to 10-15°C. To the above solution, 61.3g tetrahydrophthalimide was slowly
added in 10-15 min span and further stirred for 45 min at same temperature clear
solution was observed and then cooled to 0-2°C to obtain reaction mass. Separately,
79.8 g PCMM solution obtained in step 1 was added to above reaction mass during
15 addition precipitation was observed and stirred for 2.0 hrs at same temperature. In
work up, chlorobenzene (244 g) was charged and reaction mass was heated to 75-
80°C under stirring for 30 min and cooled to 20-25°C, filtered and the washed with
chlorobenzene (64.2 g) and hot water (74.1 g) two times to finally give an isolated
dry solid of 91.5 g. Final sulfenyl phthalimide compound specification: Yield:
20 80.54%, Purity: 97.80 % with CTC-0.008%.
Example 3:
Synthesis of 3a,4,7,7a-Tetrahydro-N-(trichloromethanesulphenyl)
phthalimide
25
Step-I: In 323.6g water, 188.8g (30%) aqueous HCl solution and carbon disulfide
(73.6 g) was charged at 5-10°C and chlorine gas was purged for 22-24 hrs at the
same temperature. After completion of reaction, layers were separated. Xylene
(48.4 gm) was added to organic mass and washed two times with 48.4 gm water.
30 194.0g crude Perchloromethyl Mercaptan (PCMM) xylene solution was obtained.
Distillation was performed of crude PCMM xylene solution on 3 feet packed
column to remove low boiler and haloalkane impurity, carbon tetrachloride (CCl4)
23
along with xylene under vacuum. The PCMM xylene solution thus obtained was
further taken for step 2. Final sulfenyl compound (the PCMM) specification:
Residual PCMM: (143.0 g). Yield: 70.40%, Purity: 88.70% with CTC-0.07%.
5 Step 2: In 302.4 g water, 33.72g (48%) NaOH solution was charged and then cooled
to 10-15°C. To the above solution, 61.3g tetrahydrophthalimide was slowly added
in 10-15 min span and further stirred for 45 min at same temperature clear solution
was observed and then cooled to 0-2°C to obtain reaction mass. Separately, 79.3g
PCMM solution obtained in step-1 was added to above reaction mass during
10 addition precipitation was observed and stirred for 2.0 hrs at same temperature. In
work up, xylene (244 g) was charged and reaction mass was heated to 75-80°C
under stirring for 30 min and cooled to 20-25°C, filtered and the washed with
xylene (64.2 g) and hot water (74.1 g) two times to finally give an isolated dry solid
of 88.0 g. Final sulfenyl phthalimide compound specification: Yield: 77.46%,
15 Purity: 97.71 % with CTC 0.0084% .
Example 4:
Synthesis of 3a,4,7,7a-Tetrahydro-N-(trichloromethanesulphenyl)
20 phthalimide
Step-I: In 323.6g water, 188.8g (30%) aqueous HCl solution and carbon disulfide
(73.6 g) was charged at 5-10°C and chlorine gas was purged for 22-24 hrs at the
same temperature. After completion of reaction, layers were separated. Ethyl
25 benzene (48.4 gm) was added to organic mass and washed two times with 48.4 gm
water. 190.0g crude Perchloromethyl Mercaptan (PCMM) ethyl benzene solution
was obtained. Distillation was performed of crude PCMM ethyl benzene solution
on 3 feet packed column to remove low boiler and haloalkane impurity, carbon
tetrachloride (CCl4) along with ethyl benzene under vacuum. The PCMM ethyl
30 benzene solution thus obtained was further taken for step 2. Final sulfenyl
compound (the PCMM) specification: Residual PCMM: (146.3 g). Yield: 71.80%,
Purity: 88.40% w/w with CTC-0.06%.
24
Step 2: In 302.4 g water, 33.72g (48%) NaOH solution was charged and then cooled
to 10-15°C. To the above solution, 61.3g tetrahydrophthalimide was slowly added
in 10-15 min span and further stirred for 45 min at same temperature clear solution
was observed and then cooled to 0-2°C to obtain reaction mass. Separately, 79.60
5 g PCMM solution obtained in step 1was added to above reaction mass during
addition precipitation was observed and stirred for 2.0 hrs at same temperature. In
work up, ethyl benzene (244 g) was charged and reaction mass was heated to 75-
80°C under stirring for 30 min and cooled to 20-25°C, filtered and the washed with
ethyl benzene (64.2 g) and hot water (74.1 g) two times to finally give an isolated
10 dry solid of 95.0 g. Final sulfenyl phthalimide compound specification: Yield:
83.6%, Purity: 98.61 % with CTC-0.0088%.
Example 5: Synthesis of Perchloromethylmercaptan (PCMM)
15
In 1664g water, 974g (30%) aqueous HCl solution and 380g carbon disulfide was
charged at 5-10°C and chlorine gas was purged for 22-24 hrs at same temperature.
After completion of reaction, layers were separated, organic mass was collected and
toluene (210 gm) was added and further organic layer was washed two times with
20 250 gm water. 905 g crude Perchloromethyl Mercaptan (PCMM) toluene solution
was obtained. Distillation was performed of crude PCMM toluene solution on 3 feet
packed column to remove low boiler and haloalkane impurity, carbon tetrachloride
(CCl4) along with toluene under vacuum. Final sulfenyl compound (the PCMM)
specification: Residual PCMM: (778.0 g). Yield: 77.0%, Purity: 92.61% with CTC25 0.07 %.
Example 6: Synthesis of N-(Trichloromethanesulphenyl)phthalimide
Step 1: In 1664g water, 974g (30%) aqueous HCl solution and 380g carbon
disulfide was charged at 5-10°C and chlorine gas was purged for 22-24 hrs at same
30 temperature. After completion of reaction, layers were separated, organic mass was
collected and toluene (210 gm) was added and further organic layer was washed
two times with 250 gm water. 905 g crude Perchloromethyl Mercaptan (PCMM)
25
toluene solution was obtained. Distillation was performed of crude PCMM toluene
solution on 3 feet packed column to remove low boiler and haloalkane impurity,
carbon tetrachloride (CCl4) along with toluene under vacuum. The PCMM toluene
solution thus obtained was further taken for step 2. Final sulfenyl compound (the
5 PCMM) specification: Residual PCMM: (778.0 g). Yield: 77.0%, Purity: 92.61%
with CTC-0.07 %.
Step 2: In 200 g water, 24 g (48%) NaOH solution was charged and then cooled to
10-15°C. To the above solution, 40.3g phthalimide was slowly added in 10-15 min
span and further stirred for 45 min at same temperature clear solution was observed
10 and then cooled to 0-2°C to obtain reaction mass. Separately, 53.98g PCMM
solution obtained in step 1 was added to reaction mass during addition precipitation
was observed and stir it for 2.0 hrs at same temperature. In work up, toluene (174
g) was charged and reaction mass was heated to 75-80°C under stirring for 30 min
and cooled to 20-25°C, filtered and the washed with toluene (45.6 g) and hot water
15 (52.6 g) two times to finally give an isolated dry solid of 55.8 g. Final sulfenyl
phthalimide compound specification: Yield: 70 %, Purity: 96.0 % .
Therefore, the fungicidal sulfenyl phthalimide compound substantially free from
haloalkane impurity was successfully prepared using a process according to the
present invention. Treatment of crude sulfenyl compound with aromatic
20 hydrocarbon results into sulfenyl compound with lesser haloalkane impurity and
the resulting sulfenyl compound further utilized for synthesizing sulfenyl
phthalimide compound substantially free from haloalkane impurity. It is to be
understood that the invention is not to be limited to the details of the above
embodiments, which are described by way of example only.

We claim:

1. A process for preparation of fungicidal sulfenyl phthalimide compound of
formula (I)
5
Formula (I)
10 wherein K together with the two contiguous linking carbon atoms, forms
a 6-membered fused aromatic ring or a fused cyclohexene ring;
said process comprising:
(a) reacting an organosulphur compound with chlorine to form a sulfenyl
compound of formula (II);
15
(b) converting said sulfenyl compound of formula (II) to a fungicidal
20 sulfenyl phthalimide compound of formula (I) substantially free from
haloalkane impurities.
2. The process as claimed in claim 1 wherein said step (a) is carried out in
presence of aqueous acidic medium and sulfenyl compound is further
treated with aromatic hydrocarbon solvent to obtain pure sulfenyl
25 compound of formula (II) substantially free from haloalkane impurities.
3. The process as claimed in claim 1 wherein said step b) comprises
converting pure sulfenyl compound of formula (II) to fungicidal sulfenyl
phthalimide compound of formula (I) by reacting sulfenyl compound of
formula (II) with a phthalimide or phthalimide derivative compound to
30 obtain sulfenyl phthalimide compound substantially free from haloalkane
impurities.
Perchloromethyl mercaptan
S
Cl Cl
Cl Cl
CS2 + Cl2
gas
HCl + water
Formula Weight = 76.0 Formula Weight = 185.88
Perchloromethyl mercaptan
(PCMM)
carbon disulfide
Step-01

Formula II
27

NH
O
O
K

Formula II Formula I
4. The process as claimed in claim 3 wherein said process is carried out in
presence of in an aqueous alkaline medium and sulfenyl phthalimide
5 compound is further treated with aromatic hydrocarbon to obtain pure
sulfenyl phthalimide compound substantially free from haloalkane
impurities.
5. The process as claimed in claim 1 wherein said haloalkene impurity is
selected from carbon tetrachloride and
10 dichloro(chlorosulfanyl)methanesulfonyl chloride or mixture thereof.
6. The process as claimed in claim 1 wherein said organosulphur compound
is selected from carbon disulfide, carbonyl sulphide or thiophosgene.
7. The process as claimed in claim 2 wherein acid used for acidic solution is
selected from hydrochloric acid, phosphoric acid or sulfuric acid.
15 8. The process as claimed in claim 4 wherein alkali used for alkaline medium
is selected from sodium hydroxide, potassium hydroxide, lithium
hydroxide or potassium carbonate.
9. The process as claimed in claim 2 or 4 wherein said aromatic hydrocarbon
is selected from toluene, chlorobenzene, ethyl benzene, propyl benzene or
20 xylene.
10. The process as claimed in claim 1 wherein said step a) is carried out at
temperature in the range from 5 to 20°C.
11. The process as claimed in claim 1 wherein said step b) is carried out at
temperature in the range from 0 to 10°C.
25 12. The process as claimed in claim 1 comprising preparation of fungicidal
sulfenyl phthalimide compound by
a) reacting carbon disulphide with chlorine in an aqueous acidic solution
to obtain a reaction mass containing perchloromethyl Mercaptan and
Perchloromethyl mercaptan
S
Cl Cl
Cl Cl
CS2 + Cl2
gas
HCl + water
Formula Weight = 76.0 Formula Weight = 185.88
Perchloromethyl mercaptan
(PCMM)
carbon disulfide
Step-01
+

28
treating the reaction mass with an aromatic hydrocarbon solvent to
obtain pure perchloromethyl mercaptan which is substantially free from
haloalkane impurities; and
CS2 + Cl2
5
b) reacting pure compound of formula (II) in an aromatic hydrocarbon
solvent with phthalimide or phthalimide derivative compound in an
10 aqueous alkaline medium to obtain sulfenyl phthalimide compound of
formula (I) substantially free from haloalkane impurities.

NH
O
O
K

15 13. The process as claimed in claim 1 wherein said compound of formula (II)
and said compound of formula of (I) is substantially free from carbon
tetrachloride impurity.
14. The process as claimed in claim 13 wherein said carbon tetrachloride
impurity is less than 0.05%.
20 15. The process as claimed in claim 1 wherein said compound of formula (II)
and said compound of formula of (I) obtained is about 98% pure.
16. The process as claimed in claim 1 wherein said sulfenyl phthalimide
compound of formula (I) is selected from 3a,4,7,7a-Tetrahydro-N-
(trichloromethanesulphenyl)phthalimide or
25 N-(Trichloromethanesulphenyl)phthalimide.
17. The process as claimed in claim 16 wherein said 3a,4,7,7a-Tetrahydro-N-
(trichloromethanesulphenyl)phthalimide compound is prepared by Perchloromethyl mercaptan
S
Cl Cl
Cl Cl
CS2 + Cl2
gas
HCl + water
Formula Weight = 76.0 Formula Weight = 185.88
Perchloromethyl mercaptan
(PCMM)
carbon disulfide
Step-01
Formula II
Formula I
Perchloromethyl mercaptan
S
Cl Cl
Cl Cl
CS2 + Cl2
gas
HCl + water
Formula Weight = 76.0 Formula Weight = 185.88
Perchloromethyl mercaptan
(PCMM)
carbon disulfide
Step-01
+
29
(a) reacting organosulphur compound with chlorine in presence an
aqueous acidic solution to obtain crude mass of perchloromethyl
mercaptan;
(b) isolating pure perchloromethyl mercaptan by treating the mass of step
5 (a) with aromatic hydrocarbon solvent; and
(c) reacting pure perchloromethyl mercaptan with tetrahydropthalimide in
presence of aqueous alkaline medium to obtain pure 3a,4,7,7aTetrahydro-N-(trichloromethanesulphenyl)phthalimide compound
substantially free from haloalkene impurities.
10 18. The process as claimed in claim 16 wherein said N-
(Trichloromethanesulphenyl)phthalimide compound is prepared by
(a) reacting carbon disulfide with chlorine in an aqueous acidic solution
to obtain crude mass of perchloromethyl mercaptan;
(b) isolating pure perchloromethyl mercaptan by treating the mass
15 obtained in step (a) with aromatic hydrocarbon solvent and
(c) reacting pure sulfenyl compound of formula (II) in aromatic
hydrocarbon with phthalimide compound in an aqueous alkaline
medium to obtain
N-(Trichloromethanesulphenyl)phthalimide compound substantially
20 free from haloalkene impurities.
19. The process as claimed in any of the preceding claims wherein haloalkene
impurity is carbon tetrachloride.
20. A process for preparation of sulfenyl compound of formula (II) comprising
(a) reacting organosulphur compound with chlorine in an aqueous
25 acidic solution to obtain crude sulfenyl compound; and
(b) treating crude sulfenyl compound of step (a) with aromatic
hydrocarbon solvent and isolating pure sulfenyl compound of
formula (II) substantially free from haloalkane impurities.
21. The process as claimed in claim 20 comprising reacting carbon disulfide
30 with chlorine to obtain perchloromethyl mercaptan and treating
30
perchloromethyl mercaptan with aromatic hydrocarbon to obtain pure
perchloromethyl mercaptan substantially free from haloalkane impurities.
22. A fungicidal sulfenyl phthalimide compound of formula (I) substantially
free from haloalkane impurities,
5
(I)
10 wherein K together with the two contiguous linking carbon atoms forms
a fused aromatic ring or a fused cyclohexene ring.
23. The compound as claimed in claim 22, wherein said compound is
3a,4,7,7a-Tetrahydro-N- (trichloromethanesulphenyl)phthalimide or N-
(Trichloromethanesulphenyl) phthalimide.
15 24. The compound as claimed in claim 23 having particle size distribution D50
of less than about 80 microns and carbon tetrachloride impurity less than
0.05%.