Rao, A V Subba

Reddy, Kusukuntla Venkat

Sabitha, G

NOPR

IndianJournalof ChemistryVol.37B, July 1998, pp. 697 - 699Synthesis of substituted isoxazoles and1,3,4-oxadiazolesKusukuntlaVenkatReddy,G Sabitha'&A V SubbaRao·Departmentof Chemistry,P G Collegeof Science,Saifabad,OsmaniaUniversity,Hyderabad500004, IndiaReceived23 September1996; accepted(revised)16 July 1997A few novel 5-(2'-hydroxyaryl)-isoxazoles 3 and 2-(aryloxymethyl)-3-mercapto-I,3,4-oxadiazoles 8 havebeen synthesized from the intermediate enaminoketones 2, and tested for their herbicidal activity.The enamino ketones 2a-el•2 constitute animportant class of synthon which can beelaborated to a wide variety of heterocycliccompounds'. These enamino ketones are readilyderived from substituted 3-formylchromones Ia-e4 in one step by treating with diethylamine inrefluxing ethanol. We report herein the synthesisof novel substituted isoxazoles 3a-e and 1,3,4-oxadiazoles 8a-e from the synthon 2. Substitutedisoxazoles and oxadiazoles in general are reportedto possess antimicrobial, antiinflammatory andsedative activities5-8•As most of the compounds 2a-e, 3a-e and 8a-eare reported for the first time, screening of theirNoteherbicidal activity has been undertaken with thehelp of Du Pont Agricultural Products, USA andthe data indicate that they possess moderateactivity.The enamino ketone 2a on treatment withhydroxylamine hydrochloride in refluxing glacialacetic acid gave 5-(0-hydroxyphenyl)isoxazole3a, mp 194-96 °C in 82% yield. Mass spectralfragmentation pattern [m/z 161 (M+), 121, 93]conflrms'v'" that the product is 5-substitutedisoxazole 3, and notthe 3-substituted compound 4(cf. Figure 1), which is reported to be a liquid.Similar reaction of substituted enamino ketones2b-e gave the corresponding isoxazoles 3b-3(Tables I and II). This constitutes an easy andelegant method of preparing exclusively 5-(0-hydroxyaryl)-isoxazoles 3 in better yields withless reaction period in comparison with earliermethods I J-13.The enamino ketones 2a-e on treatment with,phenylhydrazine in ethanol gave the phenylpyrazoles 5a-eI4• Reaction of 5 with ethylbromoacetate in acetone-Kjf'O, medium in the:presence of phase transfer catalyst gave thearyloxy acetates 6a-e. These esters were thenreacted, without further purification, withhydrazine hydrate in aqueous alcohol to get thecorresponding hydrazides 7a-e. The oxadiazolerY0H~N-()4tpresent address:Indian Instituteof ChemicalTechnology,Hyderabad.2 31,l,3,5,6.7.8 • It e d eR H CH3 a Br a~ HHHHCH3Figure 1698 INDIAN J CHEM, SEC .B, JULY 1998Table I-Yields and elemental analyses of compounds 3a-e, 7a-e and 8a-eCompd R R' Yield mp Mol. Calcd (Found) (%)(%) °C formula C H N(Mol. wt)3a H H 82 194-96 C.;I7N02 67.07 4.38 8.69(161.16) (67.17 4.29) 8.74)3b CH3 H 80 176-78 CIOH9N02 68.56 5.18 8.00(175.19) (68.47 5.28 7.973e CI H 86 206-08 C9H6CIN02 55.26 3.09 7.16(195.61) (55.19 3.12 7.193d Br H 83 214-19 C9H6BrN02 45.03 2.52 5.84(240.06) (45.11 2.46 5.91)3e CI CH3 80 236-39 CIOHsCIN02 57.30 3.84 6.68(209.63) (57.43 3.89 6.51)7a H H 74 115-17 C17HI6N402 66.22 5.23 18.17(308.34) (66.28 5.30 18.24)7b CH3 H 71 120-22 CIsH18N402 67.06 5.63 17.38(322.37) (66.98) 5.74 17.43)7e CI H 76 127-29 C17HIsCIN402 59-56 4.41 16.35(342.79) (59.55 4.51 16.33)7d Br H 81 152-55 C17HISBrN402 52.73 3.90 14.47(387.23) (52.82) 3.86 14.53)7e CI CH3 70 162-67 CIsH17CIN402 60.59 4.80 15.70(356.81) (60.66 4.86 15.61 )8a H H 72 210-12 CIsHI4N402S 61.70 4.03 15.99(350.34) 61.83 4.04 16.06)8b CH] H 75 180-82 CI9HI6N402S 62.62 4.43 15.38(364.41) (62.71 .4.35 15.29)8e CI H 78 168-70 C18HnCIN402S 56.18 3.40 14.56(384.83) (56.04 3.48 14.62)8d Br H 80 140-42 CIsHnBrN402S 50.36 3.05 13.05(429.29) (50.44 3.00 13.01)8e CI CH] 67 214-16 CI9HlsCIN402S. 57.21 3.79 14.05(398.86) (57.14 3.86 14.} 5)Table II_IH NMR data of compounds 3a-e, 7a-e and 8a-e (chemical shifts 0, pprn; Jvaiues in Hz)Compd3a3b3e3d3~7a7b7e7d7e8a8b8e8d8eIH NMR (CDCh, DMSO-d6)6.80-6.97 (m, 3H), 7.16 (s, tH), 7.77 (d, tH, .1=6.08),8.24 (d, tH, .1=4.6),9.92 (s, tH).2.34 (s, 3H), 6.86 (s, tH), 6.94 (d, tH, .1=5.26),7.04 (s, tH), 7.68 (d, tH, .1=3.16),8.30 (d, tH, .1=9.20),9.78 (bs, IH)6.83 (s, tH), 6.96 (s, tH), 7.11 (d, IH, .1=6.80),7.72 (d, tH, .1=4.21),8.25 (s, lH), 10.20 (bs, tH)6.85 (s,IH), 6.93 (d, IH, .1=2.1),7.28 (d, tH, .1=7.08),7.86 (d, tH, .1=3.15),8.30 (d, tH, .1=1.57),10.40 (bs,tH)2.28 (s,3H), 6.78 (s, IH), 6.86 (d, tH, .1=2.94), 7.69 (s, tH), 8.25 (d, tH, .1=4.5), 10.12 (bs, IH)3.66 (bs, 3H), 4.15 (s, 2H), 6.44 (s, 'IH~, 6.73 (d, 2H, .1=9.1), 7.09 (d, tH, .1=8.63), 7.32 (s,5H), 7.38 (d, 2H,.1=13.6), 7.75 (s,IH)1.55 (s, 3H), 2.29 (s, 3H), 4.08 (s, 2H), 6.38 (d, tH, .1=4.5), 6.57 (d, IH, .1=2.27), 7.26 (s, 5H), 7.72 (d, tH,J=11.4)3.73 (d, 3H), 4.15 (5, 2H), 6.53 (d, tH, J=1.36), 6.73 (d, tH, J=1.5), 7.32-7.48 (m, 7H), 7.84 (d, tH, J=9.5)2.43 (s, 3H), 4.12 (s, 2H), 6.41 (s, tH), 6.57 (d, tH, .1=9.1), 7.28-7.40 (m, 6H), 7.50 (s, tH), 7.73 (s, tH)2.32 (s, 3H), 3.6 (bs, 3H), 4.12 (s, 2H), 6.45 (s, tH), 6.63 (d, IH, .1=9.1),7.25-7.46 (m, 5H), 7.54 (bs, tH),7.74 (q, tH)4.59 (s, 2H), 6.44 (d, tH, .1=3.77), 6.89 (d, IH, .1=7.59),7.05 (d, tH, .1=7.56),7.15-7.38 (m, 7H), 7.65 (d, IH,J=2.0), 14.19 (bs, tH)2.32 (s,3H), 4.54 (s, 2H), 6.43 (d, tH, .1=4.52),6.84 (d, tH, .1=9.18),7.16 (5, 2H), 7.28 (m, 5H), 7.64 (s, tH),14.18 (5, IH)4.56(s,2H), 6.46 (d, tH, .1=1.0),6.91 (d, tH, .1=9.1),7.18-7.41 (m, 5H), 7.71 (d, tH, J=10.0), 14.7 (5, tH)4.52 (s,2H), 6.45 (d, IH, J=1.25), 6.90 (d, tH, J=9.25), 7.16-7.42 (m, 5H), 7.69 (d, tH, .1=9.75), 14.76 (s, 1H)7.25 (s,3H), 4.44(s, 2H), 6.38 (d, tH, J=3.1), 6.78 (s, tH), 7.19 (m, 5H), 7.44 (s, tH), 7.6 (d, tH, J=3.4),14.16(bs, IHJ= 13.15), 10 12 (bs, 1H)R~~N--NPh""'-R'yYO~O~'"R~N--NPh""'-s, X=H 8oIIX= -CH2 C-OEtoIIX= -CH2CNHNH27,Figure 2ring is now built by reacting 7 with CS2 and KOHin aqueous ethanol to get the title compounds 8a-e(Figure 2; Tables I and II).Experimental SectionGeneral. Melting points are uncorrected. 'nNMR spectra were determined on a VarianGemini 200 MHz spectrometer (internal SiMe4).Mass spectra were recorded on a VG micromass70-70H instrument. IR spectra were recorded on aPerkin-Elmer 1605 instrument. Thin layerchromatography was performed on Merck silicagel 60 F250 precoated plates (0.2mm).5-(2' -Hydroxyaryl)isoxazoles 3a-e (TablesI,ll). Equimolar mixture of substituted enaminoketones 2a-e (10 mmoles) and hydroxylaminehydrochloride (10 mmoles) in glacial acetic acid(5 mL) was refluxed for 1-2 hr. It was cooled toroom temperature and poured onto crushed ice togive light yellow solid which was recrystallizedfrom ethanol to afford colorless crystals of 3a-e;the yields are given in Table I.Aryloxyacetyl hydrazones 7a-e (Tables I, II).A mixture of aryloxyphenyl pyrazoles 5a-e (12mmoles), ethyl bromoacetate (14 mmoles),K2C03 (10g) and TBA HS04(2 mmoles) wastaken in acetone and refluxed for 5-7 hr. Solventwas then evaporated and the resulting aryloxyacetates 6 reacted without further purificationNOTES 699with hydrazine hydrate (15 mmoles) by refluxingm aqueous ethanol for 30 min. The resulting solidwas recrystallized from ethanol to get 7a-e ascolourless crystals; the yields are given in Table I.2-(Aryloxymethyl)-5-mercapto-l,3,4-oxadia-zoles 8a-e (Tables I,ll). A mixture of thehydrazides 7a-e (15 mmoles), carbon disulfide(18 mmoles) and potassium hydroxide (18mmoles) was refluxed in aqueous ethanol (10mL) for 4-6 hr and cooled. The resultingcrystalline solid was filtered, and recrystallizedfrom ethanol to give Sa-e as colorless crystals; theyields are given in Table I.AcknowledgementOneof the authors (AVSR) likes to express hisgratitude to Dr G Jagath Reddy, Heterocyclics,Hyderabad and Dr R Rama Krishna, Biological ELtd, for helpful discussions.References1 Ghosh C K & Khan S, Synthesis, 1981,719.2 (a) Ram B, Singh A N, Reddy C V S, Varma R K,Thomas G P, Tripathi G P & Kaushal R, Indian Drugs,28,1991, I.(b) Baker W, Harbome J W & Ollis W D, J Chem Soc,1952, 1303.3 (a) Jagath Reddy G, Sabitha G & Rao A V S, SynthCommun, 17,1987,1851.(b) Sabitha G, Jagath Reddy G & Rao A V S, SynthCommun, 18, 1988,639.4 Nohara A, Umetani T & Sanno Y, Tetrahedron Lett,1973, 1995; Tetrahedron, 30, 1974,3553.5 Ashour F A, Almazoro S & Sava A, Alexandria JPharm Sci, 4, 1990,29.6 Hazzone G, Bonina F, Puglisi E, Paniw A M & ArrigoReina R, Farma Co Ed Sci.39, 1984,414.7 Kaemmerer F J & Schlerebach R, Ger Pat, 2854438(1980); Chem Abstr, 93, 1980,239392.8 Eckhard I F, Lehtonem K, Satub T & Summers L A,Aust J Chem, 26, 1973, 2705.9 Szabo V, Borbely J, Theisz E & Nagy S, Tetrahedron,42,1986,4215.10 Rene B & Christophe M, J Org Chem, 42, 1977, 1356.II Yang I L & Lang S, J Heterocyclic Chem, 14, 1977,345.12 Woldzimierz B & Zofia J, Pol J Che~, 53, 1979,229.13 Zofia J & Woldzimierz B, Rocz Chem, 51, 1977,2283.14 Ghosh C K & Mukhopadhyay K K, J Indian Chem Soc,55. 1978. 386.

Synthesis of substituted isoxazoles and 1,3,4-oxadiazoles

http://nopr.niscair.res.in/bitstream/123456789/56849/1/IJCA%2037B%287%29%20697-699.pdf

Synthesis of substituted isoxazoles and 1,3,4-oxadiazoles

Abstract

Similar works

Full text

Available Versions

NOPR