P. Sharma, Vandana Gupta, D. Gautam
2002
Citations
1
Influential Citations
5
Citations
Journal
Heterocyclic Communications
Abstract
Synthesis of 3-bromo/l,2-dimethylphenothiazines is reported by Smiles rearrangement of 5-bromo/3,4dimethyl-2-formamido-2 '-nitrodiphenylsulfides. The later were obtained by the formylation of 2-amino-5-bromo/ 3,4-dimethyl-2'-nitrodiphenylsulfides which were prepared by the condensation of 2-amino-5-bromo/3,4dimethylbenzenethiols with o-halonitrobenzenes. INTRODUCTION Phenothiazines possess a wide spectrum of pharmacological activities (I, 2). These are used as neuroleptics (3), diuretics (4), sedatives (5), antihistamines (6), analgesics (7) etc. They have also shown significant effects against cancer (8, 9). With a slight alteration in substitution pattern, their activity can be modified to a large extent. It is considered worthwhile to synthesize hitherto unknown phenothiazines in order to make them available for biomedical screening in search of better medicinal agents. RESULT AND DISCUSSION 5-Bromo/3,4-dimethyl-2-formamido-2'-nitrodiphenylsulfides (4»^) obtained by formylation of 2-amino5-bromo/3,4-dimethyldiphenylsulfldes ( 3 Μ ) undergo Smiles rearrangement in alcoholic potassium hydroxide solution yielding 3-bromo/l,2-dimethylphenothiazines 2-Amino-5-bromo/3,4-dimethyldiphenylsulfides have been obtained by the condensation of 2-amino-5-bromo/3,4-dimethylbenzenethiols 1, prepared by the hydrolytic cleavage of 2-amino-6-bromo/4,5-dimethylbenzothiazoles adopting the method reported elsewhere (10, 11) with o-halonitrobenzens 2 in ethanolic sodium acetate solution. 2-Amino-5-bromo/3,4dimethylbenzenethiols 1 with halonitrobenzenes 2 containing a nitro group at ortho positions to halogen yields directly 3-bromo/l,2-dimethylphenothiazines 5f_| in a single step as Smiles rearrangement occur in situ due to combined resonance and inductive effect of two nitro groups (Scheme-I). Phenothiazines ( 5 M ) exhibit in IR spectra a sharp peak in the region 3385-3250 cm 1 due to NH stretching vibrations while this sharp peak in phenothiazines (5fn) which contains a nitro group at 9 position appear in the region 3310-3215 cm 1 . This shifting to lower frequency suggests a six membered chelate through (NH 0=N) hydrogen bonding (Fig. 1). 9-Nitrophenothiazines exhibit two peaks of medium intensity in the region 1570-1540 cm' 1 and 1370-1340 cm' 1 due to to asymmetric and symmetric vibrations of aromatic nitro group. In compounds 5a b f e two peaks are observed in the region 1470-1440 cm 1 and 1375-1335 cm 1 due to asymmetric and symmetric C-H deformation vibrations of CH3 groups. A single sharp peak in the region 780715 cm" in compounds is due to C-Cl stretching vibrations. In compounds 5 e J two sharp peaks are observed in the region 1330-1310 cm" and 1150-1120 cm" due to C F stretching vibrations of CF3 group. The *H NMR spectra of all phenothiazines exhibit a multiplet in the region δ 8.60-5.31 ppm due to aromatic protons. Phenothiazines 5 M , exhibit a singlet in the region δ 9.70-8.43 ppm due to NH protons, however in 9-nitrophenotiazines 5 f_j the NH proton gives rise to a singlet at δ 9.82-9.13 ppm and this downfield shift suggests hydrogen bonding between the nitro and a secondary amino groups as NH 0 = N which has also been indicated by the IR spectral data. Phenothiazines 5 > b A f . show two singlets in the region δ 3.602.22 ppm and 1.34-1.20 ppm due to CH3 protons at C-l and C-2 respectively. In the mass spectra of phenothiazines molecular ion peaks are in accordance with their molecular weights. 9-Nitrophenothiazines undergo fragmentation yielding M + -17 due to loss of OH radical due to Mc Lafferty rearrangement (Scheme-II).