{"id":340,"date":"2015-01-20T06:40:33","date_gmt":"2015-01-20T06:40:33","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=340"},"modified":"2020-04-23T11:34:38","modified_gmt":"2020-04-23T11:34:38","slug":"synthesis-and-antibacterial-evaluation-of-substituted-3-methyl-2-pyrazolin-5-ones","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol1no1\/synthesis-and-antibacterial-evaluation-of-substituted-3-methyl-2-pyrazolin-5-ones\/","title":{"rendered":"Synthesis and Antibacterial Evaluation of Substituted 3-methyl-2-pyrazolin-5-ones"},"content":{"rendered":"

Introduction<\/strong><\/p>\n

Pyrazolone moiety (a five-membered lactam ring containing two nitrogens and ketone in the same molecule or alternatively a derivative of pyrazole possessing an additional carbonyl\/hydroxy group) has been the focus of medicinal chemists for over last 100 years because of the outstanding pharmacological properties shown by several of its derivatives1,2<\/sup> e.g. ampyrone, metamizole etc. The pyrazolone ring is the basis of agents with various biological activities including antihyperglycemic properties1<\/sup>, anti-tumor necrosis factor activity3-4<\/sup>, non-steroidal anti-inflammatory drugs (NSAIDs)5<\/sup> ,inhibition of human telomerase6<\/sup> and antibacterial activity7<\/sup>. Also, substituted 2-pyrazolin-5-ones play an important role as substructures of numerous pharmaceuticals, agrochemicals, dyes, pigments, as well as chelating agents and thus attract remarkable attention8-10<\/sup>. The mentioned properties prompted us to synthesize substituted-3-methyl-2-pyrazolin-5-ones.<\/p>\n

Experimental<\/strong><\/p>\n

Material<\/strong><\/p>\n

All chemicals used in the synthesis were of analytical grade. Melting points were determined in open capillary tubes and are uncorrected. The purities of the compounds were checked on silica-gel-coated Al plates (Merck). IR spectra were recorded in KBr on a Perkin Elmer Spectrum RX-1 FT-IR spectrophotometer. 1<\/sup>H-NMR spectra was measured on Advance Bruker DRX-300. Elemental analysis was performed on Elementor Vario EL III.<\/p>\n

Synthesis of Ethyl-2-substituted phenyl hydrazono-oxobutyrate(1a-c)<\/strong> 11<\/sup><\/p>\n

Substituted aniline (o-chloro, p-chloro and p-nitro)(0.01mole) was dissolved in a mixture of concentrated HCl (8 ml) and water (6 ml) and cooled to 0o<\/sup>C in an ice bath. To it a cold aqueous solution of sodium nitrate (0.03 mole) was added. The diazonium salt solution was added dropwise into a cooled solution of ethylacetoacetate (0.01 mole) and sodium acetate (0.12 mole) in ethanol (50 ml). The resulting solid was washed with water and recrystallized with absolute ethanol.<\/p>\n

Synthesis of substituted thiosemicarbazides(2a-e)<\/strong> 12<\/sup><\/p>\n

To a solution of substituted aniline (p-methyl, o-methoxy, p-methoxy, 3,4-dimethyl and o-chloro) (0.01mole) in ammonia (20ml) and water (5ml), CS2 <\/sub>(7.5 ml) and ethanol (20ml) was added and stirred vigorously for 1 hour. Solution of Sodium carbonate(5.3 gm) and mono chloro acetic acid (9.5gm) in water (40ml) was added followed by hydrazine hydrate (6ml) and refluxed for 30-45 mins on steam bath. The resulting solid obtained on cooling was recrystallized with absolute ethanol.<\/p>\n

General method for synthesis of substituted-3-methyl-2-pyrazolin-5-one (1-15)<\/strong><\/p>\n

To 1a-e (0.01 mole), ethanol (20ml) and 2a-e (0.01 mole) was added and refluxed for 1-2 hrs in presence of 2-4 drops of glacial acetic acid.\u00a0 The resulting solid obtained was cooled, filtered and was recrystallized with hot absolute ethanol.<\/p>\n\n\n\n
\"Scheme<\/td>\n\n

Scheme 1<\/strong><\/p>\n

Click here to View Scheme<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Table 1: Physical and analytical data of compounds <\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
SI. No<\/strong><\/td>\nR<\/strong><\/td>\n\u00a0\u00a0\u00a0\u00a0 R\u2019<\/strong><\/td>\nMol. Formula<\/strong><\/td>\nColor<\/strong><\/td>\nM.P<\/strong><\/p>\n

(o<\/sup>C)<\/strong><\/td>\n

%Yield<\/strong><\/td>\n\u00a0% N<\/strong><\/p>\n

Found<\/strong><\/p>\n

(Calc.)<\/strong><\/td>\n

\u00a0% S<\/strong><\/p>\n

Found<\/strong><\/p>\n

(Calc.)<\/strong><\/td>\n<\/tr>\n

1.<\/td>\n2-Cl<\/td>\n4-CH3<\/sub><\/td>\nC18<\/sub>H16<\/sub>ON5<\/sub>SCl<\/td>\nOrange<\/td>\n195<\/td>\n80.31<\/td>\n\u00a018.18<\/p>\n

(18.15)<\/td>\n

\u00a08.41<\/p>\n

(8.30)<\/td>\n<\/tr>\n

2.<\/td>\n2-Cl<\/td>\n2-OCH3<\/sub><\/td>\nC18<\/sub>H16<\/sub>O2<\/sub>N5<\/sub>SCl<\/td>\nYellow<\/td>\n166<\/td>\n62.32<\/td>\n\u00a017.49<\/p>\n

(17.41)<\/td>\n

\u00a08.07<\/p>\n

(7.96)<\/td>\n<\/tr>\n

3.<\/td>\n2-Cl<\/td>\n4-OCH3<\/sub><\/td>\nC18<\/sub>H16<\/sub>O2<\/sub>N5<\/sub>SCl<\/td>\nOrange<\/td>\n178<\/td>\n64.80<\/td>\n\u00a017.45<\/p>\n

(17.41)<\/td>\n

\u00a08.05<\/p>\n

(7.96)<\/td>\n<\/tr>\n

4.<\/td>\n2-Cl<\/td>\n3,4-di\u00a0 CH3<\/sub><\/td>\nC19<\/sub>H18<\/sub>ON5<\/sub>SCl<\/td>\nOrange<\/td>\n165<\/td>\n60.00<\/td>\n\u00a017.56<\/p>\n

(17.52)<\/td>\n

\u00a08.12<\/p>\n

(8.00)<\/td>\n<\/tr>\n

5.<\/td>\n2-Cl<\/td>\n2-Cl<\/td>\nC17<\/sub>H13<\/sub>ON5<\/sub>SCl2<\/sub><\/td>\nYellow<\/td>\n170<\/td>\n56.43<\/td>\n\u00a017.27<\/p>\n

(17.24)<\/td>\n

\u00a07.94<\/p>\n

(7.88)<\/td>\n<\/tr>\n

6.<\/td>\n4-Cl<\/td>\n4-CH3<\/sub><\/td>\nC18<\/sub>H16<\/sub>ON5<\/sub>SCl<\/td>\nOrange<\/td>\n170<\/td>\n73.03<\/p>\n

 <\/td>\n

\u00a018.21<\/p>\n

(18.15)<\/td>\n

\u00a08.38<\/p>\n

(8.30)<\/td>\n<\/tr>\n

7.<\/td>\n4-Cl<\/td>\n2-OCH3<\/sub><\/td>\nC18<\/sub>H16<\/sub>O2<\/sub>N5<\/sub>SCl<\/td>\nOrange<\/td>\n165<\/td>\n70.35<\/td>\n\u00a017.51<\/p>\n

(17.41)<\/td>\n

\u00a08.03<\/p>\n

(7.96)<\/td>\n<\/tr>\n

8.<\/td>\n4-Cl<\/td>\n4-OCH3<\/sub><\/td>\nC18<\/sub>H16<\/sub>O2<\/sub>N5<\/sub>SCl<\/td>\nOrange<\/td>\n164<\/td>\n68.36<\/td>\n\u00a017.49<\/p>\n

(17.41)<\/td>\n

\u00a08.00<\/p>\n

(7.96)<\/td>\n<\/tr>\n

9.<\/td>\n4-Cl<\/td>\n3,4-di\u00a0 CH3<\/sub><\/td>\nC19<\/sub>H18<\/sub>ON5<\/sub>SCl<\/td>\nYellow<\/td>\n169<\/td>\n65.79<\/td>\n\u00a0\u00a017.61<\/p>\n

(17.52)<\/td>\n

8.08<\/p>\n

(8.00)<\/td>\n<\/tr>\n

10.<\/td>\n4-Cl<\/td>\n2-Cl<\/td>\nC17<\/sub>H13<\/sub>ON5<\/sub>SCl2<\/sub><\/td>\nOrange<\/td>\n155<\/td>\n61.83<\/td>\n\u00a017.30<\/p>\n

(17.24)<\/td>\n

7.92<\/p>\n

(7.88)<\/td>\n<\/tr>\n

11.<\/td>\n4-NO2<\/sub><\/td>\n4-CH3<\/sub><\/td>\nC18<\/sub>H16<\/sub>O3<\/sub>N6<\/sub>S<\/td>\nOrangish<\/p>\n

Yellow<\/td>\n

191<\/td>\n72.33<\/td>\n\u00a021.30<\/p>\n

(21.21)<\/td>\n

\u00a08.14<\/p>\n

(8.08)<\/td>\n<\/tr>\n

12.<\/td>\n4-NO2<\/sub><\/td>\n2-OCH3<\/sub><\/td>\nC18<\/sub>H16<\/sub>O4<\/sub>N6<\/sub>S<\/td>\nDarkYellow<\/td>\n194<\/td>\n53.29<\/td>\n\u00a020.37<\/p>\n

(20.31)<\/td>\n

\u00a07.72<\/p>\n

(7.76)<\/td>\n<\/tr>\n

13.<\/td>\n4-NO2<\/sub><\/td>\n4-OCH3<\/sub><\/td>\nC18<\/sub>H16<\/sub>O4<\/sub>N6<\/sub>S<\/td>\nOrange<\/td>\n168<\/td>\n50.36<\/td>\n\u00a020.39<\/p>\n

(20.31)<\/td>\n

\u00a07.73<\/p>\n

(7.76)<\/td>\n<\/tr>\n

14.<\/td>\n4-NO2<\/sub><\/td>\n3,4-di\u00a0 CH3<\/sub><\/td>\nC19<\/sub>H18<\/sub>O3<\/sub>N6<\/sub>S<\/td>\nBrick<\/p>\n

Red<\/td>\n

170<\/td>\n71.04<\/td>\n\u00a020.47<\/p>\n

(20.42)<\/td>\n

\u00a07.85<\/p>\n

(7.80)<\/td>\n<\/tr>\n

15.<\/td>\n4-NO2<\/sub><\/td>\n2-Cl<\/td>\nC17<\/sub>H13<\/sub>O3<\/sub>N6<\/sub>SCl<\/td>\nGolden<\/p>\n

Yellow<\/td>\n

190<\/td>\n61.83<\/td>\n\u00a020.13<\/p>\n

(20.16)<\/td>\n

\u00a07.63<\/p>\n

(7.68)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Table 2: Characterization data of compounds <\/strong><\/p>\n\n\n\n\n\n\n
Compound No.<\/strong><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 IR<\/strong><\/p>\n

\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 \u00a0\u00a0\u00a0(\u03bd in cm-1<\/sup>)<\/strong><\/td>\n

\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 1<\/sup>H NMR<\/strong><\/p>\n

\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 (\u03b4 in ppm)<\/strong><\/td>\n<\/tr>\n

1<\/td>\n1110 (C=S), 1571 (-N=C-, pyrazolone ring), 1674 (>C=O)<\/td>\n1.22 (s, 3H, CH3<\/sub>), 2.34 (s, 3H, CH3<\/sub>), 3.38 (s, 1H, pyrazolone ring), 4.60 (s, 1H, NH), 6.35-7.86 (m, 8H, Ar-H).<\/td>\n<\/tr>\n
6<\/td>\n1108 (C=S), 1574 (-N=C-, pyrazolone ring), 1673 (>C=O)<\/td>\n1.25 (s, 3H, CH3<\/sub>), 2.35 (s, 3H, CH3<\/sub>) , 3.36 (s, 1H, pyrazolone ring), 4.65 (s, 1H, NH), 6.42-7.70 (m, 8H, Ar-H)<\/td>\n<\/tr>\n
11<\/td>\n1115 (C=S), 1560 (-N=C-, pyrazolone ring), 1686 (>C=O)<\/td>\n1.30 (s, 3H, CH3<\/sub>), 2.37 (s, 3H, CH3<\/sub>), 3.40 (s, 1H, pyrazolone ring), \u00a04.73 (s, 1H, NH), 6.55-8.65 (m, 8H, Ar-H),<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Antibacterial screenings<\/strong><\/p>\n

Filter paper disc technique using Hi-Media agar medium is employed to study the antibacterial activity of 1-15 <\/strong>against Staphylococcus aureus and Escherichia coli. The concentration of test compounds is 1,000 \u00b5g\/ml. After 48 hr incubation at 37 o<\/sup>C, zone of inhibition produced by each compound is measured in mm as shown in Table 3. Streptomycin is used as the reference drug and Dimethyl formamide as a control.<\/p>\n

All tested compounds showed slight to moderate antibacterial activity.<\/p>\n

Key to symbols: Resistance = R; slightly active = + (inhibition zone 6-9mm); moderately active = + + (inhibition zone 9-12 mm); highly active = + + + (inhibition zone> 12 mm).<\/p>\n

Table 3: Antibacterial activity of the compounds I-XII <\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
Compound No.<\/strong><\/td>\nE. coli<\/strong><\/td>\nS. aureus<\/strong><\/td>\n<\/tr>\n
1<\/td>\n\u00a0\u00a0 ++<\/td>\n\u00a0 R<\/td>\n<\/tr>\n
2<\/td>\n\u00a0\u00a0 \u00a0+<\/td>\n\u00a0 +<\/td>\n<\/tr>\n
3<\/td>\n\u00a0\u00a0 \u00a0+<\/td>\n\u00a0R<\/td>\n<\/tr>\n
4<\/td>\n\u00a0 + +<\/td>\n\u00a0+ +<\/td>\n<\/tr>\n
5<\/td>\n\u00a0\u00a0 +<\/td>\n\u00a0 R<\/td>\n<\/tr>\n
6<\/td>\n\u00a0\u00a0 ++<\/td>\n\u00a0+ +<\/td>\n<\/tr>\n
7<\/td>\n\u00a0\u00a0 +<\/td>\n\u00a0 R<\/td>\n<\/tr>\n
8<\/td>\n\u00a0\u00a0 +<\/td>\n\u00a0 R<\/td>\n<\/tr>\n
9<\/td>\n\u00a0+ +<\/td>\n\u00a0 +<\/td>\n<\/tr>\n
10<\/td>\n\u00a0+ +<\/td>\n\u00a0R<\/td>\n<\/tr>\n
11<\/td>\n\u00a0 +<\/td>\n\u00a0 +<\/td>\n<\/tr>\n
12<\/td>\n\u00a0 +<\/td>\n\u00a0 R<\/td>\n<\/tr>\n
13<\/td>\n\u00a0++<\/td>\n+<\/td>\n<\/tr>\n
14<\/td>\n++<\/td>\n++<\/td>\n<\/tr>\n
15<\/td>\n+<\/td>\nR<\/td>\n<\/tr>\n
Streptomycin<\/td>\n+ + +<\/td>\n+ + +<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Acknowledgements<\/strong><\/p>\n

We are thankful to Central Drug Research Institute (CDRI), Lucknow for spectral and microanalysis and Dr. B.M. Agarwal, S.N.Medical College, Agra for antibacterial screenings.<\/p>\n

References<\/strong><\/p>\n

    \n
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    Introduction Pyrazolone moiety (a five-membered lactam ring containing two nitrogens […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4],"tags":[],"class_list":["post-340","post","type-post","status-publish","format-standard","hentry","category-vol1no1"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/340","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=340"}],"version-history":[{"count":5,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/340\/revisions"}],"predecessor-version":[{"id":32505,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/340\/revisions\/32505"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=340"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=340"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=340"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}