Synthesis of 5-Benzenesulphonamido-1, 3, 4-Thiadiazol 2- Sulphonamide Derivatives as an Antiepileptic Agent

A.S. Warokar*, P.S. Deshpande, A.S. Mundhey, N.J. Duragkar, N.B. Charbe, P.B. Suruse and K.P. Bhusari

Sharad Pawar College of Pharmacy, Wanadongri, Hingna Road, Nagpur-441 110 (M.S.)

*Corresponding Author E-mail: amol_warokar@rediffmail.com

ABSTRACT:

Sulphonation of 5-amino-1, 3, 4-thiadiazol-2-[N-(substituted benzoyl)] sulphonamide (4a-c) with substituted phenylsulphonyl chloride (5a-d) was carried to synthesized 5-(substituted bezenesulphonamido)-1, 3, 4-thiadiazol-2-[N-(substituted benzoyl)] sulphonamide (6a-m). As per Schotten-Boumann method, benzoylation of acetazolamide (1) and substituted benzoyl chloride (2a-c) was carried out in the presence of sodium hydroxide to form N- substitutedbenzoyl acetazolamide (3a-c) which was further hydrolysed to obtained 5-amino-1,3,4-thiadiazol-2-[N-(substituted benzoyl)]sulphonamide(4a-c). Structures of the title compound were characterized by using spectral studies like UV, IR, NMR, GC etc. They were further screened for their antiepileptic activity. Among the tested compound 5-[(Methyl) bezenesulphonamido)]-1,3,4-thiadiazol-2-[N-(4 methyl benzoyl)] sulphonamide and 5-[(Methoxy) bezenesulphonamido)]-1,3,4-thiadiazol-2-[N-(4 amino benzoyl)] sulphonamide (6h and 6k) showed better activity when compared with phenytoin sodium as a standard drug however remaining compound exhibits moderate to mild activity.

KEYWORDS: 1, 3, 4-thiadiazol, antiepileptic activity, Maximal electroshock induced seizure method, Pentylene tetrazole induced seizure method.

INTRODUCTION:

The chemistry and pharmacology of thiadiazole have been of great interest. The 1,3,4-thiadiazole moiety possess wide variety of activities such as anti-inflammatory¹, analgesic², antimicrobial³, antituberculosis⁴, antiviral⁵, anthalmentic⁶, hypoglycaemic agent⁷, antihypertensive⁸, anticholinergic⁹, herbicidal¹⁰, insecticidal¹¹, growth promoting agent¹², diuretic¹³, carbonic unhydrase inhibitors¹⁴, antiglaucoma agent¹⁵.

Attachment of sulphonamide group on 2 and 5 positions and bulkier group attachment increase antiepileptic activity. Acetazolamide which has 1, 3, 4- thiadiazole is commonly used in epileptic seizures^16,17, but it has several undesirable effect; viz., ineffectiveness after some period, metabolic acidosis, electrolytic imbalance, polyurea, tinnitus, anorexia, transient myopia, etc^18,19. Thus, another sulphonamide with bulkier group substitution on 1, 3, 4 thiadiazole may reduce these side effects and improve its bioavailability due to increase in lipophilicity²⁰.

As per Schotten-Boumann method^21,22, benzoylation of acetazolamide (1) and substituted benzoyl chloride (2a-c) was carried out in the presence of sodium hydroxide to form N- substitutedbenzoyl acetazolamide (3a-c) which was further hydrolysed to obtained 5-amino-1,3,4-thiadiazol-2-[N-(substituted benzoyl)]sulphonamide(4a-c). Later sulphonation of compound (4a-c) and substituted phenylsulhonylchloride (5a-c) carried was to yield 5-(substituted bezenesulphonamido)-1, 3, 4-thiadiazol-2-[N-(substituted benzoyl)] sulphonamide (6a-m).In this reaction acetone: water (1:1) mixture was used instead of pyridine, sodium hydroxide or any other strong base. The reaction was carefully monitored by TLC. Precoated silica gel-G plate activated at 110^° for 30 minutes were used for thin layer chromatography and the spots developed in iodine chamber. Though different solvent system was employed, R_f values were reported for better comparable solvent systems, which are mentioned in the preceding text. The compounds prepared were obtained in pure form by recrystallization from suitable solvent. The various stages involved during the synthesis have been shown in Scheme 1. Synthesized compounds have been characterized based on their physical and analytical data shown in Table 1.

The IR spectra of compounds (6a-m) shows strong band about 3110-3520cm^-1 (Ar C-H stretching), 1128 -1030 cm^-1 (S=O stretching), 1370, 1335, 1170-1155 cm^-1 (sulphonamide stretching), 1785-1735 cm^-1. The ¹H-NMR data of the compounds (6a, 6f, 6j) showing 2.172 (s,1H, Ar-SO2NH), 7.438 (s, 1H, CONH), 3.787 (s, 1H, N-H), 7.329 (m, 6H, ARr-H), 7.871 (s, 1H, thiadiazole, C-H) were in conformity with the structure.

In the GCMS spectra, molecular ion (M⁺) peaks, (which are base peak here) which appeared at different intensities, confirms the molecular weight of the compound (8a). Single intense peak in the gas chromatography reveals the purity of the compound.

EXPERIMENTAL AND RESULTS:

The chemicals, solvents employed for the synthetic work were of BDH, Hi-media, E-Merck, Loba and laboratory grad. Acetazolamide was obtained by Dr reddy’s District, (A. P.), Nakoda Chemicals Pvt. Ltd., Hyderabad and Medreich Limited, Banglore. The solvents were further purified by established methods. Few of chemicals used in synthesis were obtained from Sigma, Aldrich USA. All the residues are dried in vacuum desiccators. The melting points of the compounds were determined in open capillaries using Thermonik precision apparatus (model-C-PMP-2, Mumbai, India), are in Celsius scale and are uncorrected. Purity of the compounds was verified by precoated TLC plate’s Silica gel-G plate activated at 110 for 30 minutes. IR spectra were recorded using KBr pellets FTIR-8400s, (Shimadzu make), at Sharad Pawar College of Pharmacy, Nagpur. ¹ H-NMR spectra were recorded on Varian EM-390 Spectrophotometer (chemical shift in δ ppm) at Pune University, Pune.

Synthesis Procedure:

5-[(4-Acetamido)benzenesulphonamido]-1,3,4-thiadiazol-2-[N-(benzoyl)] sulphonamide (6a)

5-amino-1, 3, 4-thiadiazol-2-[N-(benzoyl)] sulphonamide (4a) (2 g, 0.007 mol) was suspended in a 1:1 mixture of acetone: water, and stoichometric amount of phenylsulphonyl chloride (4 a) and a base was added concomitantly. The reaction mixture was magnetically stirred for several hours, the solvent was evaporated then the pH was adjusted to 2 with 5 N hydrochloric acid and recrystillised from the aqueous ethanol and thus (6a) was obtained.

Yield: 1.2 g (35.50%), mp. 214, IR: (KBr, cm^-1) 2991-3053 (Ar C-H stretching), 1035 (S=O stretching), 1325, 1174 (sulphonamide stretching), 1663(heteroaromatic C=N). The ¹H-NMR (DMSO-d₆, d ppm) 2.172 (s, 1H, Ar-SO₂NH), 7.438 (s, 1H, CONH), 3.787 (s, 1H, N-H), 7.329 (m, 6H, ARr-H), 7.871 (s, 1H, thiadiazole, C-H), 8.611 (s, 1H, acetamido-H) were in conformity with the structure.

Adopting the above procedures, other compounds (6a-m) were synthesized and characterized. The characterized data of the compounds are given in Table-1.

Synthetic Scheme:

Antiepileptic Activity

The anti-epileptic activity of the synthesized compounds was evaluated by using two methods by using

A. MES (Maximal Electroshock induced seizure) Method:

This method is predictive of the efficiency against partial secondarily genaralised seizures.

B. PTZ (Pentylene tetrazole induced seizure) Method:

This method is predictive of efficacy against absence seizures.

Method:

The study was conducted on Norwegian strain of the rats (200-250 g body weight) of either sex. They were fasted fornight but free access to water. The animals were first tested by giving maximum current of 150 mA for 0.2 sec  duration through electroconvulsiometer (Techno Instruments, Lucknow, India) using transsuricular corneal electrodes. Only those animals showing characteristic hind limb extensor was selected.

The selected animals were divided into fourteen groups of five animals, each. The first group was control (propylene glycol 2mL/100g, oral) and the second group was for standard drug phenytoin sodium, dose: 100mg/kg, oral) and other thirteen groups were of newly synthesized compounds (dose 100mg/kg, p.o.).

The homogeneous suspension of the test compounds and the phenytoin sodium were prepared in propylene glycol and distilled water (1:9/mL). The compounds were administered orally at the dose of 100 mg/kg body weight and control group receives vehicle only, 30 minutes prior to start of the experiments. The MES were induced by an electroconvulsiometer by giving shock 150 mA for 0.2 sec, using a technique described by Swinyard et al. The duration of extension of tonus was noted. The complete abolition of the hind leg tonic extension or reduction in extension time was also noted

Table 1: Characterization data of the synthesized compounds

Comp No.	R1	R2	Mol. Formula^a (Mol. Wt.)	% Yield^a	Mp^b (^oC)	Rf	λmax (nm)	IR (KBr,  cm^-1)	NMR (DMSO-d6, d ppm)
6a	H	H	C15H12N4O5S3	35.5	214	0.65	240	3053-2991 (Ar C-H stretching), 1035 (S=O stretching), 1325,1174 sulphonamide stretching),1510 (heteroaromatic C=N)	2.172 (s,1H, Ar-SO2NH), 7.438 (s, 1H, CONH), 3.787 (s, 1H, N-H), 7.32-8.50 (m, 5H, Ar-H), 7.871 (s, 1H, thiadiazole, C-H), 8.611 (s, 1H, sulphonamido)
6b	H	Cl	C15H11N4O5S3Cl	32	218	0.68	250	3066-3011 (Ar C-H stretching), 1040 (S=O stretching), 1360,1165 sulphonamide  stretching),1487 (heteroaromatic C=N) (C-Cl stretching) (axial 730-580) equatorial 780-740)	2.22 (s,1H, Ar-SO2NH), 7.65 (s, 1H, CONH), 3.82 (s, 1H, N-H), 7.43-8.25 (m, 5H, Ar-H), 7.67 (s, 1H, thiadiazole, C-H), 8.11 (s, 1H, sulphonamido)
6c	Cl	H	C15H11N4O5S3Cl	32.5	220	0.72	245	3055-3018 (Ar C-H stretching), 1038 (S=O stretching),1355,1168 sulphonamide  stretching),1495 (heteroaromatic C=N) (C-Cl stretching) (axial 730-580) equatorial 780-740)	2.20 (s,1H, Ar-SO2NH), 7.70 (s, 1H, CONH), 3.88 (s, 1H, N-H), 7.43-8.25 (m, 5H, Ar-H), 7.67 (s, 1H, thiadiazole, C-H), 8.08 (s, 1H, sulphonamido)
6d	Cl	Cl	C15H10N4O5S3Cl2	28	234	0.67	269	3123-3010 (Ar C-H stretching), 1040 (S=O stretching),1345,1162 sulphonamide  stretching),1430 (heteroaromatic C=N) (C-Cl stretching) (axial 730-580) equatorial 780-740	2.22(s,1H, Ar-SO2NH), 7.81 (s, 1H, CONH), 3.88 (s, 1H, N-H), 7.43-8.25 (m, 5H, Ar-H), 7.67 (s, 1H, thiadiazole, C-H), 8.08 (s, 1H, sulphonamido)
6e	Br	H	C15H11N4O5S3Br	27.6	238	0.75	321	3044-3010 (Ar C-H stretching), 1175 (S=O stretching), 1350,1165 sulphonamide  stretching),1575 (heteroaromatic C=N)  (C-Br) stretching)(axial 690-550) equatorial 750-690)	2.172 (s,1H, Ar-SO2NH), 7.438 (s, 1H, CONH), 3.787 (s, 1H, N-H), 7.32-8.50 (m, 5H, Ar-H), 7.871 (s, 1H, thiadiazole, C-H), 8.611 (s, 1H, sulphonamido)
6f	F	F	C15H10N4O5S3F2	22.6	256	0.62	298	3040-3015 (Ar C-H stretching), 1173 (S=O stretching),1366,1164 sulphonamide  stretching),1572 (heteroaromatic C=N)  (C-F stretching) 1045	2.172 (s,1H, Ar-SO2NH), 7.438 (s, 1H, CONH), 3.787 (s, 1H, N-H), 7.32-8.50 (m, 5H, Ar-H), 7.871 (s, 1H, thiadiazole, C-H), 8.611 (s, 1H, sulphonamido)
6g	H	OH	C15H12N4O6S3	27.8	262	0.78	339	3062-3033 (Ar C-H stretching), 1049 (S=O stretching),1350,1160 sulphonamide   stretching),1163 (heteroaromatic C=N)  (O-H stretching) 3650- 3590),	2.18 (s,1H, Ar-SO2NH), 7.65 (s, 1H, CONH), 3.80 (s, 1H, N-H), 7.32-8.10 (m, 5H, Ar-H), 7.77 (s, 1H, thiadiazole, C-H), 8.70 (s, 1H, sulphonamido), 5.34 (s, 1H, Ar-OH)
6h	CH3	CH3	C17H16N4O5S3	25.6	256	0.63	388	3042-3011 (Ar C-H stretching), 1053 (S=O stretching),1346,1165 sulphonamide   stretching),1515 (heteroaromatic C=N) (O-H stretching) 3650- 3590), (C-H stretching) 2972-2953)	2.21 (s,1H, Ar-SO2NH), 7.84 (s, 1H, CONH), 3.80 (s, 1H, N-H), 7.65-8.23 (m, 5H, Ar-H), 7.65 (s, 1H, thiadiazole, C-H), 8.70 (s, 1H, sulphonamido), 3.82 (d, 2H, CH3^)
6i	OCH3	CH3	C17H16N4O6S3	26.7	268	0.67	369	3048-3015 (Ar C-H stretching), 1060 (S=O stretching),1352,1172 sulphonamide   stretching),1505 (heteroaromatic C=N)  (O-H stretching) 3650- 3590), (C-H stretching) 2972-2953) (CH3 – O stretching 2830-2810)	2.16 (s,1H, Ar-SO2NH), 7.68 (s, 1H, CONH), 3.86 (s, 1H, N-H), 7.65-8.23 (m, 5H, Ar-H), 7.65 (s, 1H, thiadiazole, C-H), 8.70 (s, 1H, sulphonamido), 3.76 (d, 2H, CH3^)5.34 (s,1H, Ar-OH),
6j	OCH3	OCH3	C17H16N4O7S3	27.8	257	0.74	381	3035-3007 (Ar C-H stretching), 1063 (S=O stretching),1362,1176 sulphonamide stretching),1530 (heteroaromatic C=N)  (O-H stretching) 3650- 3590), (C-H stretching) 2972-2953) ( CH3 – O stretching 2830-2810	2.19 (s,1H, Ar-SO2NH), 7.75 (s, 1H, CONH), 3.67 (s, 1H, N-H), 7.68-8.13 (m, 5H, Ar-H), 7.74 (s, 1H, thiadiazole, C-H), 8.68 (s, 1H, sulphonamido),5.28 (s, 1H, Ar-OH)
6k	OCH3	NH2	C16H15N6O6S3	29.5	267	0.64	299	3042-3014 (Ar C-H stretching), 1023 (S=O stretching),1366,1172 sulphonamide stretching),1530 (Ar C-N stretching)1340- 1250)(heteroaromatic C=N)  ( O-H stretching) 3650- 3590), ( CH3 – O stretching 2830-2810, 3217 (N-H stretching)	2.22 (s,1H, Ar-SO2NH), 7.72 (s, 1H, CONH), 3.66 (s, 1H, N-H), 7.69-8.03 (m, 5H, Ar-H), 7.71 (s, 1H, thiadiazole, C-H), 8.68 (s, 1H, sulphonamido),5.22 (s, 1H, Ar-OH)
6l	NO2	H	C15 H11N5O7S3	28.5	256	0.77	246	3032-3012 (Ar C-H stretching), 1165 (S=O stretching),1366,1172 sulphonamide  stretching),1523  (heteroaromatic C=N)  (Ar, C-NO2) 1555-1487	2.21 (s,1H, Ar-SO2NH), 7.84 (s, 1H, CONH), 3.80 (s, 1H, N-H), 7.65-8.23 (m, 5H, Ar-H), 7.65 (s, 1H, thiadiazole, C-H), 8.70 (s, 1H,sulphonamido) ,
6m	CH3	OCH3	C17H15N4O6S3	26.8	264	0.80	297	3035-3007 (Ar C-H stretching), 1063 (S=O stretching),1362,1176 sulphonamide stretching),1530 (heteroaromatic C=N)  ( O-H stretching) 3650- 3590), ( C-H stretching) 2972-2953) ( CH3 – O stretching 2830-2810	2.19 (s,1H, Ar-SO2NH), 7.75 (s, 1H, CONH), 3.67 (s, 1H, N-H), 7.68-8.13 (m, 5H, Ar-H), 7.74 (s, 1H, thiadiazole, C-H), 8.68 (s, 1H, sulphonamido),5.28 (s, 1H, Ar-OH)

Table 2: Time spend by animal (sec.) in the phases of convulsion

Time spend by animals (sec.) in phases of convulsion					Treatment dose	Sr. No.
R/D	Stupor	Clonus	Extension	Flexon
R	129	9	59	5	Control 2mL/100g	1
R	161	21	27	3		2
R	213	6	94	8		3
R	115	17	64	7		4
R	153	12	27	4		5
			54.20±28.21  (12.62)		Mean
R	70	7	11	2	Phenytoin sodium mg/kg	1
R	67	6	9	3		2
R	54	6	9	4		3
R	64	5	10	3		4
R	45	10	11	3		5
			10.00±1.00 (0.4472)		Mean
R	39	9	13	3	(6a) 100mg/kg	1
R	64	8	10	2		2
R	71	10	12	4		3
R	45	6	11	4		4
R	60	6	8	3		5
			10.80±1.924 (0.8602)		Mean
R	56	10	11	2	(6b) 100mg/kg	1
R	83	8	10	3		2
R	41	15	12	4		3
R	50	12	8	3		4
R	65	11	12			5
			10.60±1.673 (0.7483)		Mean
R	70	10	9	3	(6c) 100mg/kg	1
R	62	12	10	3		2
R	58	8	12	2		3
R	82	15	12	2		4
R	60	12	15	5		5
			11.60±2.302 (1.030)		Mean
R	85	8	13	4	(6d) 100mg/kg	1
R	61	15	10	2		2
R	81	9	9	2		3
R	58	10	16	3		4
R	68	7	12	3		5
			12.00±2.739 (1.255)		Mean
R	45	12	9	2	(6e) 100mg/kg	1
R	94	10	9	2		2
R	62	16	17	5		3
R	57	7	14	4		4
R	71	9	13	3		5
			12.40±3.435 (1.536)		Mean
R	90	16	7	5	(6f) 100mg/kg	1
R	81	14	15	3		2
R	65	9	9	2		3
R	56	13	13	4		4
R	76	7	7	4		5
			10.20±3.633  (1.625)		Mean
R	70	9	11	2	(6g) 100mg/kg	1
R	76	14	10	6		2
R	64	7	12	3		3
R	59	10	8	3		4
R	69	13	12	2		5
			10.60±1.673 (0.7483)		Mean
R	96	12	7	5	(6h) 100mg/kg	1
R	68	19	15	3		2
R	79	12	9	4		3
R	55	10	13	3		4
R	61	13	7	3		5
			10.20±3.362 (1.503)		Mean
R	56	10	18	2	(6i) 100mg/kg	1
R	83	8	13	3		2
R	41	15	10	4		3
R	50	12	16	3		4
R	65	11	11	5		5
			13.06±3.362 (1.503)		Mean
R	70	10	13	3	(6j) 100mg/kg	1
R	62	8	10	2		2
R	58	15	12	4		3
R	82	12	11	4		4
R	60	11	8	3		5
			10.80±1.924 (0.8602)		Mean
R	70	9	11	3	(6k) 100mg/kg	1
R	76	14	7	3		2
R	64	7	14	3		3
R	59	10	10	2		4
R	69	13	9	5		5
			10.20±2.588 (1.158)		Mean
R	70	10	9	3	(6l) 100mg/kg	1
R	62	12	10	3		2
R	58	8	12	2		3
R	82	15	12	2		4
R	60	12	15	5		5
			11.60±2.302 (1.030)		Mean
R	70	10	13	3	(6m) 100mg/kg	1
R	62	8	10	2		2
R	58	15	12	4		3
R	82	12	11	4		4
R	60	11	8	3		5
			10.80±1.924 (0.8602)		Mean

Mean value represented as mean of all reading ± S.D., parentheses denotes the SES (standard error of mean).

Dose of standard and test compounds was 100 mg/kg and control was 2ml/100g.

Table 3: Percentage activity with oral dose of control/standard/synthesized compounds

% Activity	Mean Extensor in sec.	Treatment
18.45	54.2	Control
100	10.0	Standard
92.59	10.8	(6a)
94.34	10.6	(6b)
86.21	11.6	(6c)
83.33	12.0	(6d)
80.65	12.4	(6e)
94.34	10.6	(6f)
80.65	12.4	(6g)
98.03	10.2	(6h)
73.53	13.0	(6i)
92.59	10.8	(6j)
98.03	10.2	(6k)
80.65	12.4	(6l)
92.59	10.8	(6m)

The following phases in the sequence and time in each phase (in seconds) was noted.

1. Tonic flexon: Contraction of muscle throughout the body and forelimbs

2. Tonic extension: Extension of extremities.

3. Clonus: Stages of relaxation after extension.

4. Stupor: Stage of unconsciousness before recovery.

  (Generally more than one minute).

The results are shown in the table 2, percentage activity reported in table 3. The synthesized compounds were compared with standard drug Phenytoin sodium.

Method B:

The anticonvulsant activity of all the synthesized was evaluated against Maximal Electroshock induced seizures method as given above. The compounds were administered i.p. at various doses from 30-120mf/kg of the body weight to mice. Thirty minutes later an i.p. dose of the 80mg/kg PTZ was given to the mice. The convulsion begins with jerk of the head and body, consisting chiefly of clonic contractions. Protection of the mice from seizures was noted. The results of Maximal Electroshock induced seizures method are shown in table 4.

Table 4: Anticonvulsant activity against PTZ induced seizures

% Protection	4h	0.5h	Compd. No.
-	-	-	Control
100	120	30	Phenytoin sodium
83.33	60	30	6a
66.66	90	60	6b
83.33	120	90	6c
66.66	120	60	6d
50	120	90	6e
66.66	60	30	6f
83.33	90	60	6g
90.00	150	90	6h
66.66	90	60	6i
66.66	90	60	6j
92.00	150	90	6k
83.33	120	90	6l
89.00	120	90	6m

RESULT AND DISCUSSION:

In the present investigation derivatives of 2,5-disulphonamido1,3,4-thiadiazole (6a-m) were synthesized. 5-amino-1, 3, 4-thiadiazol-2-[N-(substitutedbenzoyl)] sulphonamide (4a-c) were prepared by hydrolysis of the substitutedbenzoylated acetazolamide (3a-c). Compound (3a-c) were prepared from the acetazolamide by benzoylation with substitutedbenzoyl chloride (2a-c).Modified Scotten-Boumann synthesis method ¹² was used to synthesized title compound (6a-m), in which compound (4a-c) was treated with  substituted benzene where the sulphonation was made by nucleophilic substitution reaction. In this reaction, acetone: water mixture (1:1) was used instead of pyrimidine; sodium hydroxide or any other base. The thin layer chromatography was performed on precoated plates of silica gel using different solvent system and showed single spot in iodine vapour chamber. Single spot ascertained purity and homogeneity of the synthesized compounds.

The IR spectra of all compounds (6a-m) shows strong band about 3110-3520cm^-1 ( N-H stretching), 1710-1680 cm^-1 (C=O, amide stretching), 711-655 cm^-1 (C-S stretching),  1128 -1030 cm^-1 (S=O stretching), 1370,1335, 1170-1155 cm^-1 (sulphonamide stretching), 1785-1735 cm ^-1 (hetroaromatic C=N stretching).

The ¹H-NMR data of synthesized compounds δ 1.103 showing (s, 1H, Ar-SO₂H), 2.378 (s, 3H, CH₃), 3.320 (s, 1H, CONH), 4.740 (s, 1H, N-H), 7.281-7.785 (M, 6H, Ar-H), 8.025 (s, 1H, thiadiazole, C-H), 8.611 (s,1H, Acetamido-H),  were in conformity with the structure.

In the GCMS spectra, molecular ion (M⁺) peaks, (which are base peak here) which appeared at different intensities, confirms the molecular weight of the compound (6a). Single intense peak in the gas chromatography reveals the purity of the compound.

ACKNOWLEDGEMENT:

The authors are thankful to the Head, Department of Chemistry, Pune University, Pune, for recording ¹H-NMR spectra; Principal, Sharad Pawar College of Pharmacy, Nagpur for providing necessary facilities to carry out this research work.

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Received on 27.02.2012         Modified on 16.03.2012

Accepted on 25.03.2012         © AJRC All right reserved

Asian J. Research Chem. 5(5): May 2012; Page 642-649