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Convenient Synthesis of Chloromethyl Thioaromatics

K. Ramadas a;N. Janarthanan a
a
Centre for Agrochemical Research, Madras, INDIA

To cite this Article Ramadas, K. andJanarthanan, N.(1999) 'Convenient Synthesis of Chloromethyl Thioaromatics',
Synthetic Communications, 29: 6, 1003 — 1007
To link to this Article: DOI: 10.1080/00397919908086063
URL: http://dx.doi.org/10.1080/00397919908086063

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 SYNTHETIC COMMUNICATIONS, 29(6), 1003-1007 (1999)

CONVENIENT SYNTHESIS OF CHLOROMETHYL

THIOAROMATICS

K. Ramadas* and N. Janarthanan

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Centre for Agrochemical Research, SPIC Science Foundation

111, Mount Road, Guindy, Madras 600 032, INDIA.

Abstract: The work presents a simple procedure for the synthesis of the title
compounds derived from heterocyclic thiols and a bifunctional alkylating agent in
the presence of anion exchange resin.

[2-(thiocyanomethylthio)benzothioazole], (2-TCMTB) is a potential contact

fungicide for several economically important crops such as barley, cotton, corn,

wheat and is also a safer substitute to pentachlorophenol in leather processing

operations. The reported synthesis of 2-TCMTB involves use of 2-

mercaptobenzothiazole and chloromethylthiocyanate'; the latter, however,

presents difficulties in quantitative synthesis. Several patents describe the

synthesis of 1from (2-chloromethylthio) benzothiazole (2): however the synthesis

of the intermediate (2) is challenging.

NH,SCN
Acetone
SCH2SCN
2 1

To whom correspondence should be addressed

1003

Copyright 0 1999 by Marcel Dekker, Inc. www.dekker.com

 1004 RAMADAS AND JANARTHANAN

Literature is replete with several methods; thus, an aromatic thiol reportedly reacts

with formaldehyde catalysed by sodium methoxide for conversion to the

(chloromethy1)thioderivative by thionyl chloride2. Other noteworthy preparations

describe the reaction of a thiol with bromochloromethane’-*. The process is

confronted with the use of large amounts of difficultly recyclable costly

bromochloromethane. In the light of the difficulties encountered, we describe herein a

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simple procedure wherein the potassium salt of a thiol reacts with

bromochloromethane in the presence of Amberlite IRA-400. (Scheme 1)

Amberlite, yI

ArSH + BrCH,CI
(Scheme 1)

Exclusion of Amberlite IRA 400, led us to the methylenedithio diary1 derivative (3)

-
under our experimental onditions.

Acetone
ArSH + KOH + BrCH,CI ArSCH,SAr
3
With a view to improve the yields, anion exchange resin (IRA-400) was included

in the study. Use of an ion exchanger as a catalyst provides an inherent advantage

that the resin k i n g can be removed hy filtration after usc. The spcnt anion

exchanger can be rejuvenated by washing with alkali while the cation exchanger

with an acid. Thus from the reaction of a potassium salt ol a thiol with

bromochloromethane in the presence of Amherlite IRA-400,

(chloromethy1)thioheteroaromatics are obtained from heteroaromatic the

corresponding thiols Table( 1).

 CHLOROMETHYL THIOAROMATICS 1005

Table 1: Synthesis of (chloromethy1)thioaromaticsusing KOH / Amberlite

IRA 400
Entry Thiols Reaction Yield mp. ("C)
Time (h) (%)

5 84 42-43 (42-43)'

5 73 52-53 (53-54)6

qlSH
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5 72 136-138 (134)6

4 CI 5 61 85-86 (86-87)7

5 63 178-179 (177-
179)9

The intermediate (2) was subsequently converted to the thiocyanate using

ammonium thiocyanate dispersed on basic alumina. (Scheme 2).

KOH I BCH,CI

Acetone
IRA 400 Basic Alumina
SCySCN
Acdone
Scheme 2

Significant improvement in terms of convenience, yield, reaction time and

selectivity has been notcd using alumina or silica gel as support or surface for

several important reactions. This includes our own study on the surface mediated

synthesis of 0-Phosphorothioates '. The efficacy of alumina is attributed to a

combination of several factors : (i) an increase in the effective surface area for
 1006 RAMADAS AND JANARTHANAN

reaction, (ii) the presence of pores which contain both substrate and reactant and

thus lower the entropy of activation of reaction, (iii) activation of the reagent, (iv)

a synergistic effect resulting from bringing electrophile and nucleophile into

proximity, while at the same time enhancing the nucleophilicy and basicity of the

latter. Thus we have highlighted the role of alumina and anion exchanger in

working out simple and effective preparation of choloromethylthioaromatics

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which incidentally paved way for a neat, quantitative synthesis of the important

fungicide 2-TCMTB. This is generally formulated as a 30 % emulsified

concentrate commonly referred as Busan prior to application.

EXPERIMENTAL SECTION

All reagents of laboratory grade were used without purification. The melting
points are uncorrected. IR spectra were recorded on a B e e r FTIR-IFS85
spectrometer. 'H-NMR spectra were obtained on a JEOL GSX 400MHz NMR
spectrometer. I3C-NMR were recorded on a JEOL GSX lOOMHz Spectrometer.
Mass spectra were taken in a Shimadzu GC-MS QP lOOOA (70eV) mass
spectrometer . The compounds synthesised are known in the literature and their
identities are established through melting point, IR, 'HNMR,"C-NMR.

-
Preparation of chloromethylsulfides General procedure:

A solution of the thiol(lO0 mmol) and potassium hydroxide (1.12g , 20 mmol) in

acetone (15 mL), Amberlite IRA 400 (lg) was added dropwise to a stirred

mixture of bromochloromethane (19.35g, 150 mmol, 13 mL), acetone (15 mL)

and at 10" C under nitrogen . The reaction mixture was diluted with ice water and
made alkaline to remove any unconverted thiol before extraction with chloroform

(4 x 30 mL). The organic phase was washed with water (3 x 30 mL), dried

(Na2S04) and worked up to afford the desired product. (Table 1)

 CHLOROMETHYL THIOAROMATICS 1007

2-Thiocyanomethylthiobenzothiazole(2-TCMTB)

A stirred mixture of 2-(chloromethylthio)benzothiazole (21.5g, 100 mmol),

ammonium thiocyanate (7.6g, 100 mmol), acetone (20 mL) and basic alumina

(2g) was heated under reflux for 4 h. After completion of the reaction (tlc), work

up as above furnished the product. Yield 78%

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Accepted 8-8-98