Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1994-06-13
1995-06-13
Gerstl, Robert
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
548164, C07D27782, C07F 708
Patent
active
054244390
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a process for the preparation of 2-amino-4-nitrobenzothiazole derivatives of formula: ##STR3## in which R denotes an alkyl, alkoxy, alkylthio, polyfluoroalkyl, polyfluoroalkoxy, alkenyl, phenyl, alkylsulphonyl, alkoxycarbonyl, amino, cyano, sulphonamide or dialkylcarbamoyl radical.
BACKGROUND OF THE INVENTION
From Patent EP 374041 it is known to prepare certain compounds of formula (I) by nitration, using nitric acid, of the corresponding 2-aminobenzothiazoles; however, these compounds are obtained mixed with the derivatives which are nitrated in position 5 and in very low yields. This process cannot therefore be applied industrially.
DESCRIPTION OF THE INVENTION
There has now been found, and it is this which forms the subject of the present application, anew process allowing the compounds of formula (I) to be obtained industrially and in good yields.
This process consists in reacting a derivative of formula: ##STR4## in which R has the same meanings as in formula (I) with nitronium tetrafluoroborate.
This reaction is performed in an inert organic solvent such as acetonitrile or tetramethylene sulphone.
It is particularly advantageous to operate at a temperature of between 10.degree. C. and 30.degree. C. and, preferably, at approximately 20.degree. C.
The quantity of nitronium tetrafluoroborate is generally from 1 mole to 4 moles per one mole of derivative of formula (II). 2 moles of it are advantageously employed.
The reaction period is generally between 6 and 48 hours. It is generally 12 hours.
The derivatives of formula (II) are new and also form part of the invention.
The derivatives of formula (II) can be obtained by reaction of trimethylchlorosilane with the lithium derivatives of the corresponding 2-aminobenzothiazoles, the latter being obtained by the reaction of n-butyllithium with 2-aminobenzothiazoles.
This reaction is performed without isolation of the lithium derivative, in an inert solvent such as hexane, tetrahydrofuran or a mixture of these solvents, at a temperature close to -80.degree. C.
2-Amino-4-bromobenzothiazoles can be obtained by bromination of the corresponding 2-aminobenzothiazoles.
This bromination is generally performed by means of bromine, in acetic acid, at a temperature of between 20.degree. C. and 60.degree. C.
2-Aminobenzothiazoles can be obtained by the method described by L. M. Yagupolskii et al., Zh. Obshch. Khim., 33 (7), 2301 (1963).
The compounds of formula (I) can be isolated from the reaction mixture by the usual techniques for isolation (for example extraction, chromatography, crystallization).
The derivatives of formula (I) can be employed as medications or intermediates for the preparation of medications (EP 282971 and EP 374041) .
EXAMPLES
The example which follows shows how the invention may be used.
Example 1
0.68 g of nitronium tetrafluoroborate are added in small portions to a solution of 0.76 g of 2-amino-4-trimethylsilyl-6-trifluoromethoxybenzothiazole in 20 cm.sup.3 of acetonitrile cooled to 0.degree. C. Stirring is continued for 12 hours at a temperature close to 20.degree. C. The solution is then diluted with 50 cm.sup.3 of water and extracted with 2 times 50 cm.sup.3 of ethyl acetate. The organic phases are combined, dried over sodium sulphate and concentrated in vacuum. The residue is purified by flash chromatography on silica gel with a cyclohexane-ethyl acetate mixture (7-3 by volume) as eluent. After recrystallization from a cyclohexane-ethyl acetate mixture (3-2 by volume), 0.3 g of 2-amino-4-nitro-6-trifluoromethoxybenzothiazole melting at 260.degree. C. is obtained.
2-Amino-4-trimethylsilyl-6-trifluoromethoxybenzothiazole can be prepared as follows: 18.7 cm.sup.3 of n-butyllithium (1.6M in hexane) are added dropwise over 1 hour to a solution of 3.13 g of 2-amino-4-bromo-6-trifluoromethoxybenzothiazole in 50 cm.sup.3 of tetrahydrofuran under nitrogen. The solution is stirred for 45 minutes at -78.degree. C. and 6.5 g of trimethylchlorosilane are then added dropwise over 15 minu
REFERENCES:
patent: 5236940 (1993-08-01), Audiav
Chemical Abstracts, vol. 118, No. 1, 4 Jan. 1993, Columbus, Ohio, abstract no. 6906b, S. Mignani et al.
Audiau Francois
Jimonet Patrick
Mignani Serge
Gerstl Robert
Rhone-Poulenc Rorer S.A.
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