Synthesis of 2-[ 4-( 10 H-substituted phenothiazine-3-yl )-6-pyrimidin-2-phenylthiol / ol / amine / thiol ] pyrroles

2-[4-hydroxy benz-1(propene-1-one)]Pyrrole II on treatment with phenyl thiourea, guanidine carbonate, urea and thiourea in alcoholic KOH yielded compounds III, IV, V, VI which on treatment with different aryl anilines gave compounds VII, VIII, IX, X which under goes cyclisation with sulphur and iodine to give 2-[4-(10H-substituted phenothiazine-3-yl)-6pyrimidin-2-phenylthiol/-ol/-amine/-thiol] pyrrole XI (a-j), XII (a-j), XIII (aj)and XIV (a-j) respectively. The structural products were characterized by elemental analysis and spectral data.


Introduction
Heterocyclic compounds particularly five or six membered ring compounds have occupied the first place among various classes of organic compounds for their diverse biological activities 1 .A broad spectrum of biological activity is associated with both simple and fused pyrrole and a large number of natural and synthetic compounds containing such moieties find pharmaceutical applications [2][3][4][5] .Pyrimidine rings have received significant attention owing to their diverse range of biological properties.Pyrimidine nucleus is in clinical use such as antibacterial agents, anticancer agent, antiviral agents, antifungal agents and antimalarial agents.Pyrimidines have been used as therapeutic agents [6][7] possessing analgesics and antiinflammatory activity [8][9] .Several important sulfa drugs are pyrimidine derivatives namely sulfadiazine, sulfamerazine and sulfadimidine.A variety of natural products such as alkaloids also contain the pyrimidine ring system, these include hypoxanthine and xanthine, which occur in tea, and caffeine and theophylline (the constituents of tea leaves).Phenothiazine derivatives possess diverse biological activities like antiparkinsonian [10][11] , anticonvulsant 12 , antihistaminic 13 , antihelmatic 14 , antiviral 15 , antiparasitic 16 and CNS depressant 17 .

Experimental
All the melting points were determined in open capillaries and are uncorrected.The IR spectra were run in KBr on a Perkin -Elmer infrared spectrophotometer. 1 H NMR spectra on Brucker AC -300F (300 Hz) NMR spectrometer using DMSO as a solvent using tetramethyl silane as internal standard

General procedure for the preparation of the Compound (II a-m)
2-acetyl pyrrole (0.01mol) and 4-hydroxyhyde (0.01mol) was dissolved in 100ml ethanol.To this solution, NaOH (40%, 10ml) was added drop wise with constant stirring at room temperature till a dark yellow mass was obtained.The reaction mixture was kept 7-8 hr and acidified with dil HCl.The solid obtained was washed with cold water.It was filtered, dried and crystallized from appropriate solvent.These compounds (II a-m) are synthesized by classical as well as microwave assisted reaction (The paper is in press).

General procedure for the preparation of the Compound III, IV, V and VI
A mixture of benzylidene acetyl pyrroles 2a (0.01mol) and phenylthiourea, guanidine carbonate, urea, thiourea (0.03mol) in alcoholic KOH was refluxed for 8 hr.The contents were evaporated to dryness and the product so obtained was washed with water repeatedly and then recrystallized from ethanol.

General procedure for the preparation of the Compound VII, VIII, IX and X
A mixture of 2 (0.05mole) and an aromatic primary amine (0.05mole) in absolute ethanol (50ml) was heated under reflux in the presence of anhyd.ZnCl 2 (0.5g) for 6 hr.On cooling, a solid mass separated out which was washed with acidified water to remove inorganic materials, then it was filtered off to obtain the product and crystallized from ethanol.

General procedure for the preparation of compounds XI, XII, XIII and XIV
A mixture of 3 (0.01mole) sulphur (0.1 mole) and Iodine (0.5 g) was heated at 120 0 C in an oil bath for 2 hr.The hot melt was rapidly poured in to a mortar and crushed to a fine powder.It was washed with water dried and crystallized from ethanol.

Results and Discussion
The starting compound 2-acetyl pyrrole on reaction with 4-hydroxy benzaldehyde yielded 2-[4-hydroxy benz-1 / (propene-1 // -one)] Pyrrole II which on treatment with phenyl thiourea, guanidine carbonate, urea and thiourea in alcoholic KOH furnished compounds III, IV, V, VI.These then on treatment with different aromatic amines in appropriate solvent afforded VII, VIII, IX and X, which on treatment with iodine and sulphur in appropriate solvent gave the respective XI, XII, XIII and XIV.(Scheme-I).The structural products were characterized by elemental analysis and spectral data.(Tables 1-5). Scheme-I

Table 1 .
Characterization data of compounds (XI a-j)

Table 2 .
Characterization data of newly synthesized compounds (XI a-j)

Table 3 .
Characterization data of newly synthesized compounds (XII a-j)

Table 4 .
Characterization data of newly synthesized compounds (XIII a-j)

Table 5 .
Characterization data of newly synthesized compounds (XIV a-j)