Preparation of thiazine derivatives

A method for the preparation of a thiazine derivative, having insecticidal properties, of the formula ##STR1## where each R is hydrogen or an appropriate aromatic or aliphatic substituent and X is hydrogen, halogen or lower alkyl, the method comprising reacting together a sulphur donor, a compound of the formula Y.sub.2 C.dbd.CXNO.sub.2 where Y is halogen (preferably chlorine) or another appropriate leaving group and a compound of the formula EQU H.sub.2 NCR.sub.2 CR.sub.2 CR.sub.2 OSO.sub.3 H.

This invention relates to methods of preparing thiazine derivatives which 
have insecticidal activity. 
Tetrahydro-2-(nitromethylene)-2H-1,3-thiazine (I) possesses broad spectrum 
insecticidal activity, being particularly active against lepidopterous 
larvae on plants. It is also useful as an intermediate in the synthesis of 
more stable but equally active insecticides e.g., the oxime of 
5,6-dihydro-4H-1,3-thiazine-2-carboxaldehyde (II). 
##STR2## 
The two known synthetic methods for preparing compound I are outlined 
below: 
##STR3## 
Routes A and C suffer from the disadvantage that the starting material 
3-aminopropane thiol hydrochloride is expensive and the yield by route A 
is only moderate. 
Route A suffers from the disadvantage that the starting material 
3-aminopropane thiol hydrochloride is expensive and the yield by this 
route is only moderate. 
Although the starting material for Route B, 
tetrahydro-1,3-thiazine-2-thione, is relatively inexpensive the ethyl 
nitroacetate required in the second stage of the synthesis is not 
available in commercial quantities and this rules out this procedure for 
manufacturing on an industrial scale. 
According to the present invention there is provided a method for the 
preparation of a thiazine derivative of the formula 
##STR4## 
where each R is hydrogen or an appropriate aromatic or aliphatic 
substituent and X is hydrogen, halogen or lower alkyl, the method 
comprising reacting together a sulphur donor, a compound of the formula 
Y.sub.2 C.dbd.CXNO.sub.2 where Y is halogen (preferably chlorine) or 
another appropriate leaving group and a compound of the formula 
EQU H.sub.2 NCR.sub.2 CR.sub.2 CR.sub.2 OSO.sub.3 H 
Preferably, each R is independently hydrogen or lower alkyl and more 
preferably each R is hydrogen. 
The sulphur donor may be any suitable source of sulphur, for example, 
sulphur itself, a sulphide, a hydrosulphide or hydrogen sulphide. 
Preferably, the sulphur donor is an ammonium or alkali metal sulphide or 
hydrosulphide, for instance, the alkali metal sulphide sodium sulphide. 
A preferred method in accordance with the present invention may be 
represented as follows 
##STR5## 
The starting aminopropylsulphate is easily prepared from 3-amino-propanol 
and sulphuric acid. The preferred reaction referred to above proceeds at 
room temperature and this would appear to rule out a reaction mechanism 
involving the formation of the aminopropanethiol since it is known that 
the formation of the thiol only occurs at an appreciable rate at 
temperatures greater than 80.degree. C. It may be that the reaction 
mechanism involves an initial attack by the sulphide anion on the 
nitroethene in a Michael type addition. The resultant thiol anion may then 
displace the sulphate ion in the aminopropyl sulphate. Ring closure with 
the elimination of two molecules of hydrogen chloride then occurs to give 
the product. 
Because of the insolubility of the dihalonitroethylene in water it is 
preferred to use a cosolvent. Preferably, the cosolvent is a water 
immiscible organic solvent such as benzene, toluene or ethylene 
dichloride. 
Preferably, the reaction is conducted at a temperature in the range from 
0.degree.-80.degree. C. although products formed at the higher 
temperatures are relatively more contaminated and more difficult to purify 
.

EXAMPLE 
An example of a method in accordance with the present invention will now be 
described, by way of example only. 
To a stirred flask fitted with a condensor were charged water (200 ml), 
toluene (200 ml), aminopropyl sulphate (100 gms), sodium sulphide (78 
gms/60% active) and 1,1-dichloro-2-nitro ethylene (81.1 gms). The mixture 
was heated to 60.degree. C. and the pH maintained between 6-8 by gradual 
addition of sodium hydroxide solution to absorb the hydrochloric acid 
liberated. 
When the reaction was complete (about 1 hour) the reaction solution was 
cooled, the aqueous layer separated off and the pH adjusted to 5.5 with 
acetic acid. 
The aqueous layer was then extracted with methylene chloride (3 times 100 
ml). The methylene chloride was distilled out and the product 
recrystallised from isopropanol to give tetrohydro-2-(nitro 
methylene)-2H-1,3-thiazine having a melting point of 73.degree.-76.degree. 
C.