INTRODUCTION:

Heterocyclic compounds are the world’s largest and varied kinfolk of organic and synthetic routes. Cyclic imides comprising the most common heterocyclic elements like nitrogen, oxygen and sulphur plays a vital role in the development of pharmaceutical, medicinal,chemical and agricultural fields. Cyclic imides revealed the CNS anxiolytic and anti depressive activities on rats by open field test and porsolt test.^[1]Their biotransformation ofracemic and chiral forms was also susceptible on fungi.^[2]They are also remarkable region selective and stereo-selective agents by NaBH4 reduction.^[3]The molecular model methods of the substituted cyclic imides were prospectively found cytotoxic agents on DNA bindings andapoptosis induction of peripheral blood neutrophils.^[4]The substituted cyclic imides coumarins and at a coumarins confer significant antimicrobial and antifungal activities and pthalimide proven α-amylase enzymes inhibitory actions.^[5]Some halo-substituted phenyl succinimides obtained the significant role in the mechanism of NDPS nephro-toxicity NDHS formation.^[6]Succinimide acts as an electro-convulsions^[7], anti-muscarinic andnephrotoxic^[8], anticonvulsant against maximum electroshocks^[9][10][11], anti-mutagenic withanti-epileptic^[12], analgesic^[13]agents. Some optically active succinimide derivatives found good antagonistic activity towards acetylcholine on the ileum of the guinea-pigs.^[14]Cyclicimides like succinimides, maleimides, it a conimide and oxazolidinediones showed the preventive and curative antifungal potency against rice blast and kidney bean stem rots^[15]inthe green house test. They also inhibit a selective mono-glyceride lipase and psychiatricdisorders like anxiety and depression.^[16]Instead of these, the molecular polarizabilityellipsoids of the heterocyclic five membered cyclic imides are strongly interacted with othermolecular fragments which found reasonable electric properties.^[17]The numbers of succinimide derivatives have proved the seedling growth stimulator activities against Henrywheat and Scarlet globe radish ^[18]. Therefore the synthesis and selective fictionalizations ofcyclic imides has been focus of active research area over the years.^{[19] [20] [21]}

MATERIAL METHODS:

Melting points were recorded in open glass capillaries and were uncorrected. IR spectra in KBr pallets) were recorded on Simadzu and ATR Brucker alpha FT-IR spectrophotometer.¹H NMR spectra were recorded on 400 MHz and 500 MHz by Brucker spectrophotometer. The reaction was monitored by thin layer chromatography which was performed by using pre-coated silica gel aluminium plates with mixture of diethyl ether and ethyl acetate 7:3proportion. All the compounds 3a-j and 4a-j were synthesized in hours from thecorresponding commercial available aromatic amines, succinic anhydride, acetyl chloride andbenzene.

GENERAL PROCEDURE FOR CYCLIC IMIDES

Preparation of 3-(N-phenyl/napthylcarbamoyl) propanoic acid (3a-j)

To succinic anhydride (10 mmole) benzene was added and heated under reflux with constantstirring for 15 to 20 minutes till the solution becomes clear. Into this solution the primary aromatic amines / napthyl amine (10 mmole) in 5 ml benzene was slowly poured withconstant stirring for 15 to 20 minutes till the solution becomes homogenized. Uponevaporation of benzene the whitish amorphous powder of 3-(N-phenyl/napthylcarbamoyl)propanoic acid was obtained. The experimental method diagrammatically shown in fig.1;

3-(phenylcarbamoyl) propanoic acid (3a): White powder, M.F.: C10H11NO3, Mol. Wt.:193.2, M.P. 118 ºC

3-(4-bromophenylcarbamoyl) propanoic acid (3b):Shiny white powder,M. F.: C10H10BrNO3,Mol. Wt.: 272.1, M.P. 149 ºC

3-(4-chlorophenylcarbamoyl) propanoic acid (3c):White powder, M.F.: C10H10ClNO3, Mol.Wt.: 227.64, M.P. 136 °C

3-(p-tolylcarbamoyl) propanoic acid (3d): White powder, M.F.: C11H13NO3, Mol. Wt.:207.23, M.P. 146 ºC

3-(4-methoxyphenylcarbamoyl) propanoic acid (3e): White powder, M.F.: C11H13NO4, Mol.Wt.: 223.23, M.P. 151ºC

3-(4-fluorophenylcarbamoyl) propanoic acid (3f):White powder, M.F.: C10H10FNO3, Mol.Wt.: 211.19, M.P. 135 °C

3-(4-nitrophenylcarbamoyl) propanoic acid (3g):Pale yellow powder, M.F.: C10H10N2O5,Mol. Wt.: 238.2, M.P. 172 ºC

3-(naphthalen-4-ylcarbamoyl) propanoic acid (3h): Faded lavender coloured powder, M.F.:C14H13NO3, Mol. Wt.: 243.26, M.P. 111 ºC

3-(3-chloro-4-fluorophenylcarbamoyl) propanoic acid (3i):White powder, M.F.:C10H9ClFNO3, Mol. Wt.: 245.63, M.P. 124 °C

3-(2,4,5-trichlorophenylcarbamoyl) propanoic acid (3j):White powder, M.F.: C10H8Cl3NO3,Mol. Wt.: 296.53, 169 °C

Fig. 1: Experimental demonstration of cyclic imides synthesis

Preparation of N-phenyl/napthyl-pyrrolidine-2,5-dione or cyclic imides:

The mixture of 3-(N-phenyl/napthylcarbamoyl) propanoic acid and acetyl chloride (90mmole) was reflux for 15 to 20 minutes till the complete evolution of HCl gas. The reactionmixture was cooled at room temperature the solid product was obtained and purified byrecrystallization from methanol or ethanol (scheme–I) and percent yield of all the compounds were graphically shown in the chart. 1.

Phenylpyrrolidine-2, 5-dione (4a)

Cream white solid, yield (79.91%), m. p. 154-156 ºC[22],M.F.C₁₀H₉NO₂,M.W. 175.06;IR(KBr): 1708, 1774, 2937, 1291, 1457, 1502, 1595 cm^-1. 1H NMR (500 MHz, CDCl₃, δ ppm):7.1-7.42 (m, 5H, Ar-H), 2.93 (s, 4H, imide)

(4-bromophenyl) pyrrolidine-2, 5-dione (4b)

Whitish brown solid, yield (89.78%), m. p. 174-176 ºC, M.F. C₁₀H₈BrNO₂,M.W.254.08; IR(KBr): 1707,1766, 2998, 1295, 1455, 1488, 1588, 1070 cm^-1. ¹H NMR (400 MHz, CDCl₃, δppm): 7.16-7.40 (m, 4H, Ar-H), 2.95 (s, 4H, imide)

1-(4-chlorophenyl) pyrrolidine-2, 5-dione (4c)

Whitish lavender solid, yield (76.60%), m. p. 159-161 ºC, M.F. C₁₀H₈ClNO₂,M.W. 209.63;IR (KBr): 1711,1773,2985,1302, 1495, 1527, 1589, 1093 cm^-1. ¹H NMR 400 MHz, CDCl3, δppm): 7.12-7.46 (m, 4H, Ar-H), 2.89 (s, 4H, imide)

1-p-tolylpyrrolidine-2, 5-dione (4d)

Cream white solid, yield (62.73%), m. p.150-152 ºC, M.F.C₁₁H₁₁NO₂,M.W. 189.21; IR(KBr): 1710,1774,2995, 1288, 1450, 1519, 1589 cm^-1. ¹H NMR (400 MHz, CDCl₃, δ ppm):7.01-7.48 (m, 4H, Ar-H), 2.89 (s, 4H, imide), 2.31 (s, 3H, CH₃)

4-methoxyphenyl) pyrrolidine-2, 5-dione (4e)

Brownish solid, yield (78.91%), m. p.160-162 ºC, M.F. C₁₁H₁₁NO₃,M.W. 205.21; IR (KBr):1708, 1770, 2963, 1302, 1476, 1512, 1606, 1178 cm^-1. ¹H NMR (400 MHz, CDCl₃, δ ppm):6.28-7.20 (m, 4H, Ar-H), 2.91 (s, 4H, imide), 3.84 (s,3H, OCH₃)

1-(4-fluorophenyl) pyrrolidine-2, 5-dione (4f)

Brownish solid, yield (62.90%), m. p. 176-178 ºC, M.F. C₁₀H₈FNO₂,M.W. 193.17; IR (KBr):1712, 1767, 3000, 1290, 1456, 1513, 1604, 1178 cm^-1. ¹H NMR (400 MHz, CDCl₃, δ ppm):7.16-7.36 (m, 4H, Ar-H), 2.94 (s, 4H, imide)

1-(4-nitrophenyl) pyrrolidine-2, 5-dione (4g)

Cream yellow solid, yield (88.86%), m. p. 219-221 ºC, M.F.C₁₀H₈N₂O₄,M.W. 220.18; IR(ATR): 1617, 1679, 2883, 1300, 1501, 1564, 1596, 1501 cm^-1. ¹H NMR (400 MHz, CDCl₃, δppm): 7.84-8.22 (m, 4H, Ar-H), 2.91 (s, 4H, imide)

1-(naphthalen-4-yl) pyrrolidine-2, 5-dione (4h)

Dark lavender solid, yield (99.11%), m. p. 148-150 ºC, M.F. C₁₄H₁₁NO₂,M.W. 225.24; IR(ATR): 1700, 1776, 2939, 1291, 1440, 1463, 1509, 1570, 1595 cm^-1. ¹H NMR (400 MHz,CDCl₃, δ ppm): 7.30-8.03 (m, 7H, napthyl), 3.06 (s, 4H, imide)

1-(3-chloro-4-fluorophenyl) pyrrolidine-2, 5-dione (4i)

Pinkish white solid, yield (84.60%), m. p. 158-160 ºC, M.F.C₁₀H₇ClFNO₂,M.W. 227.62; IR(ATR): 1698, 1776, 2800, 1294, 1490, 1502, 1595, 1173, 1059 cm^-1. ¹H NMR (500 MHz,CDCl₃, δ ppm): 7.25-7.44 (m, 3H, Ar-H), 2.92 (s, 4H, imide)

1-(2, 4, 5-trichlorophenyl) pyrrolidine-2, 5-dione (4j)

Purewhite solid, yield (75.56%), m. p. 196-198 ºC, C₁₀H₆Cl₃NO₂, M.W. 278.52; IR (ATR):1660, 1700, 2993, 1356, 1454, 1508, 1570, 1072 cm^-1. ¹H NMR (500 MHz, CDCl₃, δ ppm):7.28-7.49 (m, 2H, Ar-H), 2.27 (s, 4H, imide)

Scheme–IPreparation of N-phenyl imides

RESULTS AND DISCUSSION:

Chemistry:

The intermediate 3a-j compounds were prepared by the reaction of succinic anhydride using primary aromatic amines and napthyl amine. The series of cyclic imides 4a-j were synthesis in reasonable yields by condensation of intermediate 3a-j with acetyl chloride formation of cyclic imides was confirmed by IR and ¹H NMR and elemental analysis.

Antibacterial activities:

All the synthesized compounds 4a-j were Screened for their antibacterial activity against gram positive bacteria Bacillus subtilis (MCMB-310) and gram negative bacteria E. coli(MCMB-301) using DMF solvent. The bacterial cultures were purchased from ARI, Pune.Some of the compound showed moderate to good activities against Bacillus subtilis and Ecolias shown in the table –1;

Table-1: Antibacterial activities of cyclic imides

Compound Code	Gram +ve bacteria			Gram -ve bacteria
	*Bacillus subtilis*			*E. coli*
	100μg/ml	200μg/ml	300μg/ml	100μg/ml	200μg/ml	300μg/ml
4a	--	8.33±0.33	11±0.57	--	8.66±0.33	11±1.15
4b	--	6.33±0.33	6.33±0.33	--	8.66±0.33	11.33±0.33
4c	--	-	8.33±0.33	7.33±0.33	9.66±0.33	12.66±0.33
4d	6.33±0.33	7.33±0.33	10.66±0.33	7±0.00	9.66±0.33	11.66±0.33
4e	--	--	--	--	10±0.00	13±0.57
4f	6.33±0.33	9±0.57	11±0.57	7.33±0.33	9.66±0.33	12.66±0.33
4g	--	--	17±0.57	7±0.57	9.33±0.33	11.66±0.33
4h	--	--	--	--	10.66±0.33	13±0.57
4i	--	7±0.00	14.33±0.33	--	9.66±0.33	12.33±0.33
4j	7±0.57	10±0.57	17±0.57	--	9.66±0.33	12±0.57
Control	0	0	0	0	0	0
Ampicillin	18.66±0.33	22.33±0.33	24±0.57	18.66±0.33	21±0.57	24±0.57

REFERENCES:

1. Pooja, Gupta Vinita, Singh Sanchita, Gupta Y.K.. “Synthesis and physico chemical characteristics of Nickel (II), Copper (II), Zinc (II), Cadmium (II) and Tin (II) complexes of schiff base with 1, 2, 4-triazole.”Journal of Ultra Scientist of Physical Sciences2017. Vol. 29(B), No 10, pp 295 - 302,

2. Sortino M., Postigo A. and Zacchino S., Effects of chirality on the antifungal potency of methylated succinimides obtained by Aspergillus fumigates biotransformation comparison with racemic ones, Molecules, 2013; 18: 5669-5683.

3. Pooja, Gupta Vinita, Singh Sanchita, Gupta Y.K.. “Synthesis, Characterization and Anti-microbial Activity of Some Schiff’s Bases of 1, 2, 4-Triazole”. Journal of Ultra Chemistry, 2017, Vol. 13, No 06, pp 132 - 139,

4. Kumar Arun, Gupta Vinita, Singh Sanchita, Gupta Y.K. “Synthesis of Some Chalcone and Their Heterocyclic Derivatives as Potential Antimicrobial Agents: A Review”. Asian Journal of Research in Chemistry, 2017,Vol. 10, No 02, pp 225-239,

5. Marulasiddaiah R., Kalkhambkar R.G., Kulkarni M. V., Synthesis and biological evaluation of cyclic imides with coumarins and azacoumarins, Open Journal of Medicinal Chemistry, 2012; 2: 89-97.

6. Kumar Arun, Gupta Vinita, Singh Sanchita, Gupta Y.K.. “Synthesis and Physico Chemical Studies of Some Chalcone and Their Derivatives as Potential Antimicrobial Agents.” Research Journal of Pharmacy and Technology (RJPT) 2017,Vol.10, Issue 05, pp 951-958.

7. Luszczki J. J., Marzeda E., Kondrat-Wrobe M. W., Wrobel J.,Kocharov S. L. and Florek-Luszczki M., Effect of N-(p-ethoxy-carbonyl-phenyl-methyl)-p-isopropoxyphenylsuccinimide on the anticonvulsant action of four classical antiepileptic drugs in the mousemaximal electroshock-induced seizure model,Journal of Preclinical and ClinicalResearch, 2014; 8(1): 34-37.

8. Gupta Y.K., Agarwal S.C., “Study of Antimicrobial activities of Schiff bases”, Journal of ultra-chemistry, Vol. 7, No 3,2011 pp 493-502.

9. Gupta Yogesh Kumar,GuptaVinita,SinghSanchita “Synthesis, Characterization and Antimicrobial activity of Pyrimidine based derivatives”. Journal of Pharmacy Research, (Elsevier) Vol. 07, No. 06,2013 pp 491-495.

10. Kaminski K. Obniska J. Chlebek I, Liana P. and Pekala E., Synthesis and biological properties of new N-Mannich bases derived from 3-methyl-3-phenyl and 3,3-dimethylsuccinimides Part V., European Journal of Medicinal Chemistry, 2013; 66: 12-21.

11. Obniska J., Rzepka S. and Krzysztof K. S., Synthesis and anticonvulsant activity of new N-Mannich bases derived from 3-(2-fluorophenyl)- and 3-(2-bromophenyl)-pyrrolidine- 2,5-diones. Part II, Elsevier, Bioorganic and Medicinal Chemistry, 2012; 20: 4872-4880.

12. Pekalaa E., Lianaa P., Kubowicza P., Powroznika B., Obniska J., Chebekb I., Wegrzync A. and Wegrzyn G., Evaluation of mutagenic and anti-mutagenic properties of new derivatives of pyrrolidine-2,5-dione with anti-epileptic activity, by use of the Vibrio harveyi mutagenicity, Elsevier, Mutation Research, 2013; 758: 18-22.

13. Gupta Y.K., Agarwal S.C.,SharmaDilip “Synthesis and biological activities of 2-Methyl-4-N-2-cyanoethyl-N-substituted benzaldehydes and their derivatives”, Asian Journal of Research in Chemistry, Vol. 5, No 2,2012 pp 245-247.

14. Gupta Y.K., Agarwal S.C., “Physical characterization of some complexes of nitrogen donor compounds”, International Journal of Chemical Engineering, Vol. 4, Issue 2,2011 pp 147-158

15. Gupta Vinita, Singh Sanchita and Gupta Y.K. “Synthesis and Antimicrobial Activity of some Salicylaldehyde Schiff bases of 2-aminopyridine”. Research Journal of Chemical Sciences, Vol. 03, Issue09, 2013 pp 26-29.

16. Matuszak N., Muccioli G. G., Labar J. and Lambert D. M., Synthesis and evaluation of N-substituted maleimide derivatives as selective monoglyceride lipase inhibitor, Journal of Medicinal Chemistry, 2009; 52: 7410-7420.

17. Prezhdo V. V., Kowalski P., Kowalska T., Zubkova V. V., Olan K. and Prezhdo O. V., Molecular polarizability anisotropy of some five-membered cyclic imides, Elsewhere, Journal of Molecular Structure, 2011; 997: 20-29.

18. Gupta Y.K.,Agarwal S.C., "Synthesis and antimicrobial activity of new 4-thiazolidinone derivatives containing 2-amino-6-ethoxybenzothiazole", Asian Journal of Research in Chemistry, Vol. 4, No 12, 2011pp 1245-1252.

19. Patil M. M. and Rajput S. S., Succinimides: Synthesis, Reaction and Biological activity, International Journal of Pharmacy and Pharmaceutical Sciences, 2014; 6(11): 8-14. 20.

20. Rajput S.S., Synthesis and Characterization of Bis-Heteroyclic Derivatives of 1-(3- Chlorophenyl)-Pyrrolidine-2, 5-Dione, International Journal of Advances in Pharmacy, Biology and Chemistry, 2012; 1(2): 242-246.

21. Gupta Vinita,Singh Sanchita, Gupta Y.K. “Synthesis and Antimicrobial Activities of Zn(II) Complex of 2,5-diamino-1,3,4-thiadiazole”. Research Journal ofSciences and Technology, Vol. 05, Issue04, 2013 pp 462-465.

22. GuptaY.K,Gupta Vinita, Singh Sanchita. “Synthesis, characterization and antibacterial activity of some 4-Thiazolidinones derivatives”. Asian Journal of Research in Chemistry, Vol. 05, No 9,2012 pp 1155-1158

Received on 06.12.2017 Accepted on 28.12.2017

Int. J. Tech. 2017; 7(2): 85-89.

DOI: 10.5958/2231-3915.2017.00014.1