Nitroimidazoles: Part IX. Addition of diazomethane to 1-methyl-5-nitro-2-acylamino- & 2-Sulphonamidoimidazoles & to 2-Dichloracetamido-5-nitrothiazole

Abstract

1-Methyl-2-dichloracetamido-5-nitroimidazole (3) undergoes an anomalous reaction with diazomethane to give imidazo(4,5-c)pyrazoJes (8) and (9). the reaction proceeding by the initial formation of 2-dichIoracetylimino-l.3-dimethyl-4-nitroimidazoline (6). cycloaddition of diazomethane to the nitroethylene bond in (6), elimination of nitrous acid from the adduct leading to imidazopyrazole(7) and subsequent alkylation of 7 at either of the two pyrazole nitrogen centres. Two less frequently encountered byproducts are 5 arising from the expected N-methyldichloracetamide(4)and the ring-opened amidine (12). The formation of 12 from 6 is rationalized. I -Methyl-2-p-toluenesulphonamido-5-nitroimidazole( 14) undergoes a similar reaction with diazomethane to form in addition to the exo(15)-and endo(16)-N-methyl derivatives, imidazopyrazoles (17, 18 and 20) by cycloaddition of diazomethane to 16. Two N -methyl carbamoyl derivatives (19) and (21) of 17 are byproducts of the reaction, arising from 17 by interaction with methyl isocyanate contaminating diazomethane. and have been prepared from it by deliberate treatment with methyl isocyanate. Two further byproducts, the imidazoline (22) and the related amidoxime(23) resulted from addition of methanol to nitroimidazoline (16) to form 24 followed by standard transformations. The cycloaddition reaction is shown to be a general one, by isolation of thiazolopyrazoles (27 and 28) by treating 2-dichloracetylamino-5-nitrothiazole (26) with diazomethane. Extensive use of ¹³C NMR spectroscopy has helped structural assignments, in particular, in differentiating isometric pairs, 8, 9; 15, 16: 18, 20; and 27, 28. Further, it is of diagnostic value in providing insight into the tautomeric nature of 3 (as 3a), 7 (as 7a). 14 (us 14b) and 17 as (I7a).