Synthesis, Characterization and AntimicrobialActivity of Some new

1,4 Diaryl-3-Methyl-6-Imino-4,7-Dihydro-1,3-Thiazino (5,4-d) Pyrazoles

 

A.K. Yadav*¹, Mazhar Mehdi^2*, Tasneem Fatima³

¹Prasad Inst. of Technology, Jaunpur (U.P.)

²Asst. Prof.,Chemistry Dept. , Shia P G College, Lucknow (U.P.)

³Asst. Prof.,Chemistry Dept. , Dr. A.H.R. Shia Degree College Jaunpur (U.P.)

*CorrespondingAuthorE-mail:drmazharmehdi@gmail.com

Pyrazolones (1) react with aromatic aldehydes to give 1-aryl-3 methyl-4-arylidene pyrazol-5-ones(2).. The condensation of 4-arylidene-pyrazol-5-ones (2) with thiourea/N-phenyl thiourea in alcoholic KOH led to formation of the title compounds 1,4-diaryl-3-methyl-6-imino-4,7-dihydro-1,3-thiazine (5,4-d) pyrazoles (3). The title compounds have been screened for their antibacterial activity against S. aureus andE.coli.

 

 

 

 

INTRODUCTION:

In heterocyclic chemistry pyrazolones and pyrazole derivatives have unique position in the field of medicine¹, industry² and agriculture³. Pyrazolone derivatives ^4-12 have found application as antibacterial, antifungal, anti-inflammatory, anticonvulsive, anti-hypertensive, antimalarial, antitumer and herbicidal agents. These useful application⁴ofpyrazolone derivatives have prompted us to synthesise some new 1,4-diaryl-3-methyl-6imino-4,7-dihydro-1,3-thiazino (5, 4-d) pyrazoles. The antibacterial activity of synthesized compounds have been screened against S. aureus and E. coli.

 

1-Aryl-3-methylpyrazo1-5-ones(1)werepreparedbyknownmethod.Thecompound(1)condensedwithdifferentarylaldehydeinglacialaceticacidtoyield1-aryl-3-methyl-4-arylidenepyrazol-5-ones(2).Thecompounds(2)wererefluxedwith thiourea/ N-phenylthiourea in ethanolicKOHsolutionfor 3-4hrs.togivethetitlecompound 1,4-d diaryl-3-methyl-6-imino-4,7-dihydro-1,3-thiazino(5,4-d)pyrazo1es(3)(Scheme-1).

 

 

Ar= phenyl and 2,4-Dinitrophenyl; R= H and  phenyl

X= H; p-NO₂ ; p-OCH₃ ; m--OCH_{3 ;} p-NMe₂

Scheme-1

 

 

 

ANTIMICROBIAL   ACTIVITY:-

The compounds (3a-x) were screened for their antibacterial activity against S. aureus and E. coli by known methodl¹⁴ at concentrations of 1000, 100 and 10 ppm and the percentage of inhibition noted after 48 hrs. The compound number (3x) was found to be more active among all the tested compounds. The reference commercial bactericide was Ampicillin.  Other compounds showed moderate bactericidal activity. lt is noteworthy that the antibacterial activity decreases upon  dilution.

 

EXPERIMENTAL:

All the melting points were taken in an open capillary tubes and are uncorrected.  The  lR  spectra   were  recorded  in  KBr  on  Jasco   FT/ IR-5300 spectrometer. The ¹H-NMR spectra were recorded in CDCl₃ on Varian A-60 D spectrometer. The chemical shifts are recorded in ppm  downfield from TMS, which  were used  as an internal standard.

 

1-Aryl-3-methyl-4-arylidene pyrazol-5-ones (2) (General Procedure):

A mixture of (1) (0.01mole) and different aryl aldehyde (O.O1 mole) in glacial acetic acid (20ml) was heated into conical flask on  sand  bath  for  15 minutes and left overnight at room  temperature.  The compound  (2)  was separated  as coloured  crystal, filtered, dried  and  recrystallised  from  benzene.

 

1,4-Diaryl-3-methyl-6-imino-4,7-dihydro-1,3-thiazino(5,4-d)pyrazoles (3) (General Procedure):-

A mixture of compound (2) (0.0 mole),  thiourea / N-phenyl  thiourea (0.01 mole) and KOH (0.02 mole) was refluxed  in ethanol  (30 ml) for 3-4  hrs. The reaction mixture was cooled at room temperature, it was acidified with dil.  HCl and diluted it by addition of 20-30 ml water to get solid material. It was filtered, dried  and  recrystallized   from  ethanol.

 

The physical data of the synthesized compounds are given in Table- 1. All the compounds gave satisfactory  elemental  analyses.

 

TABLE-1

Comp No.	Ar	R	X	M.P (0C)	Yield (%)	I.R. (KBr) vcm-1	1H NMR (CDCl3),ppm
3a	Phenyl	H	H	198	53	1690(C=O) 1570(C=N) 3398 (NH)	1-8 (3H,s,CH3), 3.8(1H,s,S-CH) 7.0-7.8 (10H,m,Ar-H) 9.3 (2H,s,NH) and D2O Exchangeable
3b	Phenyl	H	p-NO2	165	60	1695 (C=O) 1560 (C=N) 3400 (NH)	2.0 (3H,s,CH3) 3.6 (1H,s,S-CH) 7.4-8.1 (9H,m,Ar-H) 9.1 (2H,s,NH) and D2O exchangeable
3c	Phenyl	H	m-NO2	145	58	1685 (C=O) 1565 (C=N) 3395 (NH)	2.0 (3H,s,CH3) 3.7 (1H,s,S-CH) 7.5-8.1 (9H,m,Ar-H) 9.2 (2H,s,NH) and D2O exchangeable
3d	Phenyl	H	p-OCH3	125	63	1700 (C=O) 1570 (C=N) 3390 (NH)	2.1 (3H,s,CH3) 3.7 (1H,s,S-CH) 3.9 (3H,s,OCH3) 7.4-8.3 (9H,m,Ar-H) 9.3 (2H,s,NH) and D2O exchangeable
3e	Phenyl	H	m-OCH3	120	56	1690 (C=O) 1770 (C=N) 3395 (NH)	1.9 (3H,s,CH3) 3.6 (1H,s.S-CH) 4.0 (3H,m,OCH3) 7.5-8.2 (9H,m,Ar-H) 9.2 (2H,s,NH) and D2O exchangeable
3f	Phenyl	H	p-NMe2	183	72	1695 (C=O) 1565 (C=N) 3390 (NH)	1.8 (3H,s,CH3) 2.8 (6H,s,NMe2) 3.7 (1H,s,S-CH) 7.6-8.5 (9H,m,Ar-H) 9.1 (2H,s,NH) and D2O exchangeable
3g	Phenyl	Phenyl	H	205	50	1700 (C=O) 1570 (C=N) 3385 (NH)	2.0 (3H,s,CH3) 3.7 (1H,s,S-CH) 7.1-8.1 (15H,m,Ar.-H) 8.9 (1H,s,NH) and D2O exchangeable
3h	Phenyl	Phenyl	p-NO2	178	62	1705 (C=O) 1570 (C=N) 3400 (NH)	1.8 (3H,s,CH3) 3.6 (1H,s,CH) 7.2-8.1 (14H,m,Ar-H) 9.0 (1H,s,NH) and D2O exchangeable
3i	Phenyl	Phenyl	m-NO2	155	60	1695 (C=O) 1568 (C=N) 3395 (NH)	2.1 (3H.s.CH3) 3.8 (1H.s.CH) 7.4-8.2 (14H.m.Ar-H) 9.0 (1H.S.NH) and D2O exchangeable
3j	Phenyl	Phenyl	p-OCH3	135	54	1700 (C=O) 1575 (C=N) 3388 (NH)	2.0 (3H.s.CH3) 3.7 (1H,s,S-CH) 4.0 (3H.s.OCH3) 7.2-7.9 (14H,m,Ar-H) 9.1 (1H,s,NH) and D2O exchangeable
3k	Phenyl	Phenyl	m-OCH3	130	58	1690 (C=O) 1565(C=N) 3390 (NH)	2,1 (3H,s,CH3), 3.6 (1H,s,CH) 3.9 (3H,m,Ar-H) 6.9-8.0 (14H,m,Ar-H) 9.2.(1H,s,NH) and D2O exchangeable
3l	Phenyl	Phenyl	p-NMe2	194	71	1698 (C=O) 1676(C=N) 3385 (NH)	2.0 (3H,s,CH3), 3.0 (6H,s,NMe2) 3.8 (1H,s,S-CH) 6.4-7.9 (14H,m,Ar-H) 9.2.(1H,s,NH) and D2O exchangeable
3m	2,4-Dinitro phenyl	H	H	240	55	1685 (C=O) 1580(C=N) 3395 (NH)	1.9 (3H,s,CH3), 3.8 (1H,s,S-CH) 6.3-7.1 (8H,m,Ar-H) 9.0.(2H,s,NH) and D2O exchangeable
3n	2,4-Dinitro phenyl	H	p-NO2	265	63	1690 (C=O) 1575(C=N) 3390 (NH)	1.9 (3H,s,CH3), 3.6 (1H,s,S-CH) 6.2-7.0 (7H,m,Ar-H) 9.2.(2H,s,NH) and D2O exchangeable
3o	2,4-Dinitro phenyl	H	m-NO2	212	60	1700 (C=O) 1575(C=N) 3400 (NH)	2.0 (3H,s,CH3), 3.7 (1H,s,S-CH) 6.4-7.3 (7H,m,Ar-H) 9.1.(2H,s,NH) and D2O exchangeable
3p	2,4-Dinitro phenyl	H	p-OCH3	250	66	1695 (C=O) 1580(C=N) 3398 (NH)	2.1 (3H,s,CH3), 3.6 (1H,s,S-CH) 3.8 (3H,s,OCH3) 6.1-7.0 (7H,m,Ar-H) 9.2.(2H,s,NH) and D2O exchangeable
3q	2,4-Dinitro phenyl	H	m-OCH3	225	59	1680 (C=O) 1565(C=N) 3395 (NH)	1.9 (3H,s,CH3), 3.6 (1H,s,S-CH) 4.0 (3H,s,OCH3) 6.3-7.2 (7H,m,Ar-H) 9.1.(2H,s,NH) and D2O exchangeable
3r	2,4-Dinitro phenyl	H	p-NMe2	255	70	1690 (C=O) 1575(C=N) 3390 (NH)	2.0 (3H,s,CH3), 2.9 (6H,s,NMe) 3.7 (1H,s,S-CH) 6.2-7.0 (7H,m,Ar-H) 9.2.(2H,s,NH) and D2O exchangeable
3s	2,4-Dinitro phenyl	phenyl	H	263	57	1685 (C=O) 1580(C=N) 3400 (NH)	1.8 (3H,s,CH3), 3.8 (1H,s,S-CH) 6.2-6.9 (13H,m,Ar-H) 8.9.(1H,s,NH) and D2O exchangeable
3t	2,4-Dinitro phenyl	phenyl	p-NO2	224	60	1685 (C=O) 1578(C=N) 3385 (NH)	2.0 (3H,s,CH3), 3.7 (1H,s,S-CH) 6.4-7.1 (12H,m,Ar-H) 9.1.(1H,s,NH) and D2O exchangeable
3u	2,4-Dinitro phenyl	phenyl	m-NO2	271	64	1695 (C=O) 1575(C=N) 3395 (NH)	2.0 (3H,s,CH3), 3.8 (1H,s,S-CH) 6.3-7.1 (12H,m,Ar-H) 9.0.(1H,s,NH) and D2O exchangeable
3v	2,4-Dinitro phenyl	phenyl	p-OCH3	236	59	1700 (C=O) 1580(C=N) 3388 (NH)	1.9 (3H,s,CH3), 3.7 (1H,s,S-CH) 4.0 (3H,s,OCH3) 6.2-7.2(12H,m,Ar-H) 9.2(1H,s,NH and D2O exchangeable
3w	2,4-Dinitro phenyl	phenyl	m-OCH3	229	62	1690 (C=O) 1580(C=N) 3385 (NH)	2.1 (3H,s,CH3), 3.6 (1H,s,S-CH) 3.9 (3H,s,OCH3) 6.4-7.3(12H,m,Ar-H) 9.0(1H,s,NH and D2O exchangeable
3x	2,4-Dinitro phenyl	phenyl	p-NMe2	270	68	1695 (C=O) 1577(C=N) 3390 (NH)	2.0 (3H,s,CH3), 2.8 (6H,s,NMe2) 3.8 (1H,s,S-CH) 6.2-7.1(12H,m,Ar-H) 8.9(1H,s,NH) and D2O exchangeable

 

 

 

ACKNOWLEDGEMENT:

The authors are very grateful to the Principal and Head, Department of Chemistry, T.D.P.G. College, Jaunpur for providing necessary facilities and also to Dr. M.S. Singh, B.H.U. Varanasi for providing spectral suggestions. Thanks are also due to Dr. R.K. Asthana (Ex. Associate Prof., Chemistry Dept.) R.S.K.D.P.G. College, Jaunpur for Valuable suggestions.

 

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Received on 17.12.2017         Modified on 15.01.2018

Accepted on 05.02.2018         © AJRC All right reserved