Process for Preparing l,2-Benzisothiazolin-3-ones
This invention relates to processes for making 1,2-benzisothiazolin-3-ones. More
especially but not exclusively the invention relates to methods for making N-substituted
l,2-benzisothiazolin-3-ones. l,2-benzisothiazolin-3-one sometimes referred to as BIT is
known as a biocide. 2-methyl-l,2-benzoisothiazolin-3-one, CAS# 2527-66-4, sometimes
referred to as Me-BIT is a biocide and fungicide. Other N-substituted 1,2
benzoisothiazolin-3-ones have biocidal and or fungicidal properties.
CA 1269985 and US 4727188 describe processes for preparing 1,2-
benzisothiazolin-3-ones. In a first step and as described in US 4727188 anthranilamide is
nitrosated by reaction with a nitrite (ie nitrate III) followed by reaction with sulfur dioxide
to give 2,2'-dithiodibenzamide. It is well known that nitrosation is implicated in the
formation of nitrosoamines which can be a health hazard and the reaction is in any event
difficult to perform on an industrial scale. As an alternative to this reaction 2,2'-
dithiodibenzamides can be made from the corresponding acyl chloride but according to US
4 727 188 this reaction is difficult to perform.
The ensuing 2,2'-dithiodibenzamide is then subjected to oxidative ring closure. The
reaction is performed in alkaline conditions in the presence of oxygen or an oxygen donor
such as a peracid in CA 1 269 985.
The invention seeks to provide alternative processes for preparing 1,2-
benzisothiazolin-3-ones.
A process for preparing a compound of Formula I
where R is H or C\ -C straight or branched chain a ky
comprising the steps of
i) heating a mixture of sodium sulfide hydrate and N-methyl-2-pyrrolidone
ii) distilling from the mixture water and optionally at least a portion of the N-methyl-
2-pyrrolidone to leave water-depleted sodium sulfide and optionally water and/or Nmethyl-
2 pyrrolidone,
iii) reacting at least one benzamide substituted at the 2-position with a leaving group
preferably selected from the group consisting of -CI, -F, -Br, sulfonate such as sulfonic
acid, sulfonate ester such as tosyl, mesyl and benzenesulfonyl, -N0 2, -CN, carbonyl such
as carboxylic acid and ester functionality such as -COOR' where R' is Ci-C branched or
straight chain alkyl, trichloromcthyl or trifluoromethyl and -OR" where R" is Ci-C
branched or straight chain alkyl and optionally substituted at the amide functionality by a
Ci-C straight or branched chain alkyl group with the water-depleted sodium sulfide and
iv) subjecting the product to oxidative cyclisation. The oxidative cyclisation can be
effected using sulfuryl chloride, hydrogen peroxide or dimethylsulfoxide. In some
embodiments the oxidative cyclisation is effected by aqueous hydrogen peroxide. In some
embodiments the at least one benzamide is substituted at the 2-position by -CI. Where the
amide functionality is substituted the substituent is preferably is selected from the group
consisting of methyl, ethyl, propyl, iso-propyl, butyl, 2-methylpropyl, -methylpropyl, tbutyl,
pentyl, hexyl, 2-ethylhexyl and octyl. Step iii) can be effected by heating at a
temperature in the range 100 to 200°C for a time in the range 1 to 5 hours. Step i) and ii)
can be effected in the presence of toluene or xylene.
2-mercaptobenzamide is a known material. It is described for example in
JP06345723. According to that document 2-mercaptobenzamide can be made by the
reaction of 2-halobenzamide with 60% sodium sulfide. The authors of that document
contend that when 2-chlorobenzamide is used as the starting material the yield of 2-
mercaptobenzamide is 85%. No information of the purity of the 2-mercaptobenzamide is
given. The present inventors have repeated the process set forth in Example 1 of
JP06345723. The results are set forth herein and show that the yield of pure 2-
mercaptobenzamide is low. The purity of the obtained 2-mercaptobenzamide was 56% and
the yield based on 2-chlorobenzamide was 43%. The present invention flows from the
present inventors' realisation that the large by-product fraction is due to the use of 60%
sodium sulfide. The remainder of the crude sodium sulfide is water which hydrolyses the
amide functionality of the benzamide.
Commercially available sodium sulfide is available only as the hydrate and
contains considerable water. It is not available in industrially useful amounts in anhydrous
form. It is possible to produce anhydrous sodium sulphide in the laboratory by reaction of
sodium with sulfur in liquid ammonia but this technique is too expensive for industrial
scale use.
In accordance with an aspect of the invention, in an initial step a sodium sulfide
hydrate which is usually obtained in the form of lumps, flakes or powder is slurried with
N-methyl-2-pyrrolidone (hereinafter sometimes referred to as "NMP") and heated in a dry
atmosphere, for example under dry nitrogen, until at least some of the water is evaporated
optionally with some of the N-methyl-2-pyrrolidone. Typical heating temperatures are
between the boiling point of water and the boiling point of N-methyl-2-pyrrolidone at the
pressure at which the transformation is taking place. At ambient pressure this implies a
temperature in the range of about 100 to about 200°C; preferably the temperature is about
150, 160 or 170 to about 0 or 200°C. The process is not restricted to ambient pressure
and other pressures either higher or lower may be used. In preferred embodiments the
process is performed at reduced pressure such as 50 to 850 hPa (mbar), in particular from
100 to 400 hPa, preferably from 150 to 350 hPa, since less energy is required than at
atmospheric pressure. In preferred embodiments of the invention toluene or xylene is also
present since this aids water removal using Dean-Stark type apparatus. These materials can
also aid in slurrying of the sodium sulfide.
The dried sodium sulfide is then reacted with 2-chlorobenzamide. It is found that
much less 2-chlorobenzoic acid is formed compared to when untreated sodium sulfide is
used. Additionally next to no starting material remains unreacted. Additionally a small
amount of 2,2'-dithiodibenzamide is formed in addition to the 2-mercaptobenzamide. This
is not a problem since 2,2'-dithiodibenzamide itself undergoes oxidative cyclization to
form BIT. Similar results are obtained using other 2-halobenzamides such as 2-
bromobenzamide and especially 2-fluorobenzamide. Other suitable 2-substituted
benzamides include those substituted at the 2-position by sulfonate such as sulfonic acid,
sulfonate ester such as tosyl, mesyl and benzenesulfonyl -N0 2, -CN, carbonyl such as
carboxylic acid and ester functionality such as -COOR' where R' is C -C branched or
straight chain alkyl, trichloromethyl or trilfuoromethyl and -OR" where R" is Ci-C6
branched or straight chain alkyl . Examples of Ci- branched or straight-chain alkyl
include methyl, ethyl, propyl, isopropyl, or butyl.
In like manner, when it is desired to prepare N-substituted l,3-benzothiazol-3-one a
2-substituted-N-aIkylbenzamide is used. The nature of the alkyl substituent is chosen
depending on the structure of the target.
In place of sodium sulfide other sulfides (SH ) can be used, especially those of
potassium, lithium and ammonium. These materials are generally anhydrous and so it is
not necessary to conduct the drying step.
In principle mercaptobenzamide can be isolated either in free form or as a salt and
purified, but in practice it is not often necessary to isolate the product in pure form. The 2-
mercaptobenzamide or salt thereof can then be oxidatively cyclised for example using
hydrogen peroxide to give l,2-benzisothiazolin-3-one or its salts. Other suitable reagents
for oxidative cyclisation may include molecular oxygen for example air, ozone, sodium
chlorate (I), sodium perborate, sodium percarbonate, sodium perphosphate, potassium
permanganate, ruthenium tetroxide, osmium tetroxide and organic peroxides such as
MCPBA, peracetic acid, perbenzoic acid, and perphthalic acid. The preferred oxidative
cyclisation reagent is however an aqueous solution of hydrogen peroxide. Preferably the
aqueous solution of hydrogen peroxide contains less than about 68wt hydrogen peroxide
on safety grounds. Suitable concentrations may be in the range of about 3 t% to about
68wt% for example about 6wt% to about 30wt% such as about 10 to 20wt% for example
about 14wt%.
In some embodiments the oxidative cyclisation is performed in N-methyl-2-
pyrrolidone. Other solvents such as dimethyl sulfoxide, dimethylformamide, dioxane,
hexamethylphosphorotriamide, acetonitrile, tetrahydrofuran, water, alcohols such as
methanol or ethanol, ketones such as acetone and methyl ethyl ketone, esters such as ethyl
acetate, sulfolane, 2-pyrrolidone, 1,2-dimethyl imidazole, 1,3-dimethylimidazolidine,
dimethyl sulfone, l,3-dimethyl-3,4,5,6-tetrahydro-2(lH)-pyrimidone ("DMPU"),
dimethylacetamide and acetamide can be used.
The hydrogen peroxide solution may function as a solvent and in some
embodiments it is not necessary to add further solvent. Particularly good results are
however achieved with dimethyl sulfoxide but N-methyl-2-pyrrolidone also gives good
results.
Typically the reaction mixture containing the at least partially dried sodium sulfide
is cooled to about 130°C for example in the range about 0 to about 160°C and then the
substituted benzamide compound such as chlorobenzamide is added. The mixture is then
allowed to react. In order to speed the reaction it may be desirable to heat the mixture for
example to a temperature in the range about 150 to about 190°C. If wished it is possible to
monitor progress of the reaction by for example HPLC. Those skilled will have little
difficulty in selecting suitable analytical techniques.
When the reaction is sufficiently advanced the mixture is allowed to cool.
In some embodiments any excess sodium sulfide can be destroyed by adding a
mineral acid such as hydrochloric acid and boiling until hydrogen sulfide evolution ceases.
This however is not preferred since the evolved highly toxic hydrogen sulfide has
to be disposed of. In preferred embodiments the hydrogen sulfide is destroyed in situ for
example by an excess of the oxidizing agent such as hydrogen peroxide, dimethyl
sulfoxide and mixtures thereof.
Aqueous hydrogen peroxide is added slowly and once all the peroxide has been
added the mixture is worked up by distilling off the water and N-methyl pyrrolidone.
The l,2-benzisothiazolin-3-one salt can be removed from the reaction mixture for
use or can be converted to the 1,2-benzisothiazolin-3-one by reaction with an acid such as
hydrochloric acid.
While 2-chlorobenzamide is preferred on cost grounds to produce the 2-
mercaptobenzamide it is also possible to use 2-fluorobenzamide, 2-bromobenzamide or
other benzamides having an electron withdrawing group at the 2-position such as nit -.
cyano-, sulfonate such as sulfonic acid, sulfonate ester such as tosyl, mesyl and
benzenesulfonyl, carbonyl groups such as carboxylic acid and ester functionality such as
COOR' where R' is C1-6 branched or straight chain alkyl, trichloromethyl or
trifiuoromethyl and -OR" where R" is C1-6 branched or straight chain alkyl. 2-
Fluorobenzamide and 2-chlorobenzamide are especially preferred.
Preferred embodiments of the invention are one-pot reactions in which initially
sodium sulfide hydrate is heated with the polar aprotic solvent until sufficient water has
been driven off (for example as determined by weight loss) then adding the benzamide and
after a further period cooling the mixture and subjecting it to oxidative cyclisation.
Commercial sodium sulfide generally is supplied as the hydrate, a S.x - O, where
the percentage of Na2S is specified. It is therefore a straightforward matter to calculate how
much water is present in the sodium sulfide hydrate. Desirably it is heated with the Nmethyl-
2-pyrrolidone until much for example at least 50%, more preferably at least 60%
such as at least 70% of the water for example at least 80% or at least 90% or even 100% or
substantially all of the water is driven off. This can be determined by weighing, by
analytical techniques known to the skilled in the art or by spectroscopy. Alternatively the
mixture can simply be heated for a period known by experiment or experience to be long
enough.
Example 1 (Comparative)
The process for synthesis of 2-mercaptobenzamide, set forth in example 1 of JP 06
345723 was repeated:
15.6 g (0.0983 mol) of 98% 2-chlorobenzamide, 16.0g (0.1230 mol) of 60%
sodium sulfide and lOOg NMP were added to a 200ml 3 neck flask provided with a stirrer,
heated oil bath thermometer and condenser. The mixture was stirred at 160°C for 4 hours.
NMP was distilled off at reduced pressure and the residue dissolved in lOOg of
water.
The mixture was acidified to pH 4.0 by adding 35% hydrochloric acid at 20°C.
The separated crystalline material was isolated by filtration, washed with water and
dried to constant weight of 1.6 g at 40°C.
HPLC analysis, calibrated by authentic samples, revealed the following
composition of the isolated product:
(g mol; molar% of theory): (1.2; 0.0071 ; 7.2) 2-chlorobenzamide, (2.8; 0.0177;
18.0) 2-chlorobenzoic acid and (6.5; 0.0424; 43.2) 2-mercaptobenzamide.
Based on weight the purity of 2-mercaptobenzamide is 56.0%.
Example 2
23. 4g (0.18 mol) of 60% sodium sulfide (40% water) and 160g N-methyl-2-
pyrrolidone (NMP) was added to a 500ml 3 neck flask provided with a heated oil bath,
stirrer and a thermometer. The mixture was stirred at 190°C and purged with nitrogen to a
weight loss of 25g. To the dried slurry of sodium sulfide at 130°C, 18.1g (0.1 163 mol), 2-
chlorobenzamide of 98%o purity was added and the mixture heated to 175°C for 4 hours.
HPLC analysis of the reaction mixture, calibrated with authentic samples showed (g; mol;
molar % of theory): (0.37; 0.0012; 2) 2,2'-dithiodibenzoic acid and (16.5; 0.108; 88) 2-
mercaptobenzamide. 2-chlorobenzoic acid was not detected.
The mixture was cooled to 70°C, 40g of water was added and pH adjusted to 4.0,
by adding 28. 5g of 35% hydrochloric acid. The mixture was heated to boiling until
hydrogen sulfide evolution ceased. Evolved hydrogen sulfide was absorbed for disposal in
a caustic solution. At 20°C, caustic solution (such as alkali hydroxide or carbonates or
other salts or other bases) was added to the reaction mixture to bring the pH back to 9 or
above and 27.Og (0.1 11 mol) 14% hydrogen peroxide was introduced over 30 min.
Water and NMP was distilled off at reduced pressure and the residue was dispersed
in 125g of water. The mixture was adjusted to pH5with 35% hydrochloric acid. Separated
BIT crystals were filtered off, washed with water and air dried to constant weight. BIT
yield 14.3g (0.094 mol) which is 80.8% of theory. Purity 99.5% by HPLC. The NMP can
be recovered for reuse by known methods.
Example 3
23.4g (0.12 mol) of 60% sodium sulfide (40% water) and 160g N-methyl-2-
pyrrolidone (NMP) was added to a 500ml 3 neck flask provided with a heated oil bath
stirrer and a thermometer. The mixture was stirred at 190°C and purged with nitrogen to a
weight loss of 25g. To the dried slurry of sodium sulfide at 130°C, 8.1g (0.1 17 mol), 2-
chlorobenzamide was added and the mixture heated to 175°C for 4 hours. HPLC analysis
of the reaction mixture, calibrated with authentic samples showed (g; mol; molar % of
theory): (0.37; 0.0012; 2) 2,2'-dithiodibenzoic acid and (16.5; 0.108; 88) 2-
mercaptobenzamide. 2-chlorobenzoic acid was not detected. NMP was distilled off at
reduced pressure.
The mixture was cooled to 70°C, 125g of water was added and pH adjusted to 3.0,
by adding 28.5g of 35% hydrochloric acid. The mixture was heated to boiling until
hydrogen sulfide evolution ceased. Instead of boiling hydrogen sulfide evolution could be
promoted by a gas stream. Evolved hydrogen sulfide can be absorbed in a caustic solution
for disposal. At 20°C, caustic solution (such as alkali hydroxide or carbonate or other salts
or other bases) is added to the reaction mixture to bring the pH back to 9 or above. 27. g
(0.1 11 mol) 14% hydrogen peroxide was introduced over 30 min.
The mixture was acidified to pH 5 with 35% hydrochloric acid and the BIT crystals
filtered off, washed with water and air dried to constant weight. The yield and quality of
BIT was the same as in Example 2.
Example 4
23.4g (0.12 mol) of 60% sodium sulfide (40% water) and 160g N-methyl-2-
pyrollidone (NMP) was added to a 500ml 3 neck flask provided with a heated oil bath,
stirrer and a thermometer. The mixture was stirred at 130°C and water followed by
water/NMP, then NMP is distilled off under vacuum until about 10wt% of the total
reaction mixture was distilled off. The oil bath temperature was adjusted to maintain
distillation. The reaction mixture was cooled down to 130°C. To the dried slurry of sodium
sulfide at 130°C, 18. lg (0.1 17 mol), 2-chlorobenzamide (which can be dissolved in NMP
or other inert organic solvent such as aprotic polar solvent) was added and the mixture
heated to 175°C for 4 hours under nitrogen. HPLC analysis of the reaction mixture,
calibrated with authentic samples showed completion of reaction (<0.5% of starting
material. 2-Chlorobenzoic acid was not detected.)
At 20°C, caustic solution (such as alkali hydroxide or salts such as carbonates or
other bases) was added to the reaction mixture to bring the pH to 9 or above. 27.Og (0.1 11
mol) 14% hydrogen peroxide was introduced over 30 min and the mixture stirred until
completion of reaction. If necessary more hydrogen peroxide was added. The solvents
(water and NMP) were distilled off under vacuum and the residue is taken back in water.
The aqueous mixture was acidified to pH 4 with 35% hydrochloric acid and the BIT
crystals were filtered off, washed with water and air dried to constant weight. The yield
and quality of the BIT was the same as in Example 2.
Example 5
Example 4 was repeated up to the point where the reaction of 2-chlorobenzamide
with sodium sulfide was complete.
The solvent (NMP) was distilled off under vacuum and the residue taken back in
water.
At 20°C, caustic solution (such as alkali hydroxide or carbonate or other salts or
other bases) was added to the reaction mixture to bring the pH to 9 or above.27.0g (0.1 11
mol) 14% hydrogen peroxide was introduced over 30 min. The reaction mixture was
stirred until completion of reaction if necessary with the addition of further hydrogen
peroxide. The aqueous solution was acidified to pH 5 with 35% hydrochloric acid and BIT
crystals filtered off, washed with water and air dried to constant weight. The yield and
quality of BIT was the same as in Example 2.
Example 6
Example 4 was repeated until the reaction of 2-chlorobenzamide with sodium
sulfide was complete.
The solvent (NMP) was distilled off under vacuum and the residue treated with
DMSO.
At 20°C, potassium carbonate (or alkali hydroxide or other base) was added to the
reaction mixture to bring the pH to 9 or above. 27.Og (0.1 1 mol) 14% hydrogen peroxide
was introduced over 30 min and the mixture stirred until reaction was complete. If
necessary more hydrogen peroxide was added. DMSO was distilled off under vacuum and
the residue was stirred with toluene for 30 minutes. The solid was decanted and rinsed with
toluene. It was then treated with water and then acidified to pH 5 with 35% hydrochloric
acid. BIT crystals were filtered off, washed with water and air dried to constant weight.
The yield and quality was the same as in Example 2
Example 7
Example 4 was repeated until the reaction of 2-chlorobenzamide with sodium
sulfide was complete save that 7.4g (0.0569 mol) of 60%> sodium sulfide (40% water),
133g (NMP) and 6.0g (0.03856 mol), 2-chlorobenzamide were employed.
NMP was distilled off under vacuum and the residue was taken back in water.
The reaction mixture was acidified to pH 6.0 with concentrated HC1, and then
potassium carbonate powder was added to bring the pH to 10.5. Hydrogen peroxide was
added to the reaction mixture. The ensuing reaction was followed by HPLC sampling and
once substantially complete the reaction mixture was acidified to pH4.5 at temperature
<10°C resulting in precipitation of BIT. The reaction mixture was stirred for at least 1 hour
at <10°C, then the BIT was filtered under vacuum. The cake was washed with water and
dried. Yield 80% purity 97%.
Example 8
Example 4 was repeated save that in place of 2-chlorobenzamide 16.3g (0.1 17
mol), 2-fluorobenzamide was used. The reaction was substantially faster than when 2-
chlorobenzamide was used and was complete in 65 minutes at 170°C as compared with
240 minutes at 175°C when 2-chlorobenzamide was used.
Example 9 Preparation of 2-methyl-f,2-benzisothiazoIin-3-one
50g N-methyl-2-pyrrolidone (NMP) was added to a 100ml 3 neck flask provided with a
heated oil bath, stirrer and thermometer. 6.6g (0.0507mol) of 60% sodium sulfide (40%
water), 7.0g of water and 19.3g of xylene was added to the reaction flask. At a bath
temperature of 50°C water and xylene was distilled off into a Dean and Stark receiver.
The bath temperature was raised further to 220°C to distil off remains of xylene. To the
dried slurry of sodium disulfide in NMP, a solution of 6.0g (0.0347mol) 2-chloro-Nmethylbenzamide
in 12g NMP was added with stirring at 175°C over 20 min. and the
reaction continued for a further 2.5 hrs. The mixture was cooled to 30°C. The pH is
adjusted to 4.0 with 35% hydrochloric acid and the mixture is heated to 120°C for a short
while to expel hydrogen sulfide and water. To the stirred reaction mixture at 25°C 4.7g
(0.0347mol) of sulfuryl chloride was added over 15 min and stirring was continued for a
further 60 min. HPLC analysis showed a conversion of 2-chloro-N-methylbenzamide to
2-methyl- l,2-benzisothiazolin-3-one of 74.1 molar%.
Example 10: Preparation of 2-methyl-f ,2-benzothiazohn-3-one
A mixture of sodium sulfide (-60%, 19. 8g, 0.152mol), xylene (49g), water (18.9g) and
NMP (160.3g) in a reaction flask equipped with condenser and Dean-Stark trap was heated
to reflux. After removal of water the xylene was distilled off by increasing the oil bath
temp to 220°C. The mixture was allowed to cool to 175°C and a solution of 2-chloro-Nmethylbenzamide
(18.0g, 0.105mol) in NMP (40.7g) added dropwise. The mixture was
heated at 175°C for 4 hours.
The mixture was concentrated in vacuo to one third volume and allowed to cool to 40°C.
Water (75 g) was added and the pH adjusted to 4 by addition of 35% hydrochloric acid
(24. 3g). The mixture was heated to 90°C with nitrogen sparging for 60 minutes to expel
residual hydrogen sulphide to afford a suspension of a sand coloured solid and brown
supernatant solution (total weight = 135. 3g). A 7.3g portion of the above suspension was
stirred at room temperature and diluted with water (5ml) and acetonitrile ( 0ml) and
treated with sodium hydrogen carbonate (l.Og, 12.0mmol) and hydrogen peroxide (33% aq
solution, 0.95ml, 1.04g, 10.5mmol, added in 4 portions over a 4 hour period). HPLC
analysis showed 2-methyl-l,2-benzothiazolin-3-one as the main reaction component in
58.1mol% yield.
Example 11: Preparation of 2-butyI-l,2-benzothiazoiin-3-one
A mixture of sodium sulfide (-60%, 9.9g, 0.076mol). xylene (25. 7g). water (9.8g) and
NMP (79. 7g) in a reaction flask equipped with condenser and Dean-Stark trap was heated
to reflux. After removal of water the xylene was distilled off by increasing the oil bath
temp to 220°C. The mixture was allowed to cool to 175°C and a solution of 2-chloro-Nbutylbenzamide
( .l , 0.052mol) in NMP (20g) added dropwise. The mixture was heated
at 175°C for 4 hours. The mixture allowed to cool to 40°C and 35% hydrochloric acid
(13.7g) was added until the pH was adjusted to 4. The mixture was heated to 90°C with
nitrogen sparging for 20 minutes and then the temperature was raised to 130°C for a
further 60min to expel residual hydrogen sulfide and water to leave a suspension of a sand
coloured solid and reddish brown supernatant solution (total weight = 95. 6g). An 8.85g
portion of the above suspension was treated with sulfuryl chloride (0.3ml, 0.5g,
3.70mmol), added in four aliquots with 20min between additions. HPLC analysis showed
2-butyl-l,2-benzothiazolin-3-one as the main reaction component in 74.1mol% yield.
Example 12: Preparation of 2-butyl-l,2-benzothiazolin-3-one
A mixture of sodium sulfide (~60%, 9.9g, 0.076mol), xylene (25. 7g), water (9.8g) and
NMP (79.7g) in a reaction flask equipped with condenser and Dean-Stark trap was heated
to reflux. After removal of water the xylene was distilled off by increasing oil bath temp to
220°C. The mixture was allowed to cool to 175°C and a solution of 2-chloro-Nbutylbenzamide
( 1 l.lg, 0.052mol) in NMP (20g) added dropwise. The mixture was heated
at 175°C for 4 hours. The mixture was allowed to cool to 40°C and 35% hydrochloric acid
(13.7g) was added until the pH was adjusted to 4. The mixture was heated to 90°C with
nitrogen sparging for 20 minutes and then the temperature was raised to 130°C for a
further 60min to expel residual hydrogen sulfide and water to leave a suspension of a sand
coloured solid and reddish brown supernatant solution (total weight = 95.6g). An 8.85g
portion of the above suspension was stirred at room temperature and diluted with water
(10ml) and acetonitnle (5ml) and treated with sodium hydrogen carbonate (0.60g,
7.2mmo!) and hydrogen peroxide (33% aq solution, 0.73ml, 0.80g, 7.96mmol, added in 5
portions). HPLC analysis showed 2-butyl-l,2-benzothiazolin-3-one as the main reaction
component in 41mol% yield.

Claims
1. A process for preparing a compound of Formula I
I
where R is selected from the group consisting of H or Ci-Cg straight or branched chain
alkyl,
said process comprising the steps of
heating a mixture of sodium sulfide hydrate and N-methyl-2-pyrrolidone
ii) distilling from said mixture water and optionally at least a portion of said Nmethyl-
2-pyrrolidone to leave water-depleted sodium sulfide and optionally water and/or
N-methyl-2-pyrrolidone,
iii) reacting at least one benzamide substituted at the 2-position with a group selected
from the group consisting of -Cl,-Br, -F, -N0 2, -CN, sulfonate, sulfonate ester such as
tosyl, mesyl and benzene sulfonyl, carbonyl groups such as carboxylic acid and ester
functionality such as -COOR' where R' is C1- branched or straight chain alkyl,
trichloromethyl or trifluoromethyl and -OR" where R" is C1-6 branched or straight chain
alkyl and optionally substituted at the amide functionality by a C1-C8 straight or branched
chain alkyl group with the water-depleted sodium sulfide and
iv) subjecting the product of step iii) to oxidative cyclisation.
2. A process as claimed in claim 1 wherein the oxidative cyclisation is effected by a
reagent selected from sulfuryl chloride, hydrogen peroxide or dimethylsulfoxide.
3. A process as claimed in claim 2 wherein the oxidative cyclisation is effected by
aqueous hydrogen peroxide.
4 . A process as claimed in claim 1 wherein the at least one benzamide is substituted at
the 2-position by CI.
5 . A process as claimed in claim 1 wherein the amide functionality of the at least one
benzamide is not substituted.
6 . A process as claimed in claim 1 wherein the substituent at the amide functionality
is selected from the group consisting of methyl, ethyl, propyl, iso-propyl, butyl, 2-
methylpropyl. 1-methylpropyl, t-butyl, pentyl, hexyl, 2-ethylhexyl and octyl.
7. A process as claimed in claim 1 wherein step iii) is effected by heating at a
temperature in the range 100 to 200°C for a time in the range 1 to 5 hours.
8. A process as claimed in claim 1 step i) and ii) are effected in the presence of
toluene or xylene.