1976 619Heterocycles from Ylides. Part 111.l Reactivity of Allylic PhosphoniumYlides with I ,3-DipolesBy Piero Dalla Croce,' lstituto di Chimica lndustriale dell'UniversitB di Milano, C.N.R. Centro di Studio sullaDonato Pocar, lstituto di Chimica Organica della FacoltB di Farmacia dell'UniversitB di Milano, Viale AbruzziSintesi e Stereochimica di Speciali Sisterni Organici, Via Golgi 19, 201 33 Milano, Italy42, 20131 Milano, Italy3-Cyano-, 3-formyl-, and 3-methoxycarbonyl-allylidenetriphenylphosphorane react with nitrile imides and nitrileoxides yielding the corresponding substituted pyrazoles and isoxazoles, through elimination of a methyltriphenyl-phosphonium salt. The differences in reactivity between the foregoing phosphoranes and simple carbonyl-stabilised phosphoranes are discussed.THE reaction between hydrazonyl halides and carbonyl-stabilised phosphonium ylides affords pyrazole deriva-t i v e ~ .~ . ~ This synthesis is an easy entry to some classesof pyrazoles such as 5-alkoxy- and 5-dialkylamino-substituted compounds.We now report the use of stabilised allylic phosphoniumylides in the preparation of pyrazoles and isoxazolederivatives by reaction with 1,3-dipoles. The ylidesemployed are vinylogues of carbonyl-stabilised phos-phoranes widely used in the synthesis of heterocycle^.^^^Br Ph,;-CH,-CH : CH.CN (113-Cyanoallylbiphenylphosphon~um bromide (1) wasprepared in 85% yield by treatment of 4-bromocrotono-nitrile with triphenylphosphine in acetonitrile at roomtemperature. The phosphonium salt was convertedinto the ylide by reaction with aqueous sodium hydroxideas described for 3-met hoxycarbonylallylidene- and3-formylallylidene-triphenylphosphorane (2b and c) .The IH n.m.r.spectrum of the ylide (2a) showed itsconfiguration to be trans, as already known for (2b andTreating solutions of the crystalline ylides (2a-c) inchloroform with various 1,3-dipoles (e.g. nitrile imidesand nitrile oxides) resulted in an extremely cleanaddition reaction leading, in good yield, to the corres-ponding pyrazole and isoxazole derivatives (4) (Scheme1 Parts I and 11, P. Dana Croce, Ann. Chim. (Italy), 1973, 63,2 R. Fusco and P. Dalla Croce, Chimica e Industria, 1970, 52,* P. Dalla Croce, Ann. Chim. (Italy), 1973, 63, 867.6 Y .Hagashi, T. Watanabe, and R. Oda, Tetrahedron Letters,c) .9867, 896.45.G. R. Harvey, J . Org. Chem., 1966,31, 1587.1970, 605.1). The structures of the products (4a-f) were con-sistent with their lH n.m.r. spectra and elementalanalyses.R'CH 'CR2 R'C-CR~ I1 + 11 + 11 1 1 +MebPh, X-Ph,b--EH-CH - / N H C y NY( 2 ) ( 3 ) ( 4 ) ( 5 )Cryst.R1 R2 Y M.p. ("C) solvent Yield(4a) CN C0,Me NPh 170-171 MeOH 75(4b)' C0,Me C0,Me NPh 99-100 MeOH 80C0,Me Ph NPh 102-103 MeOH 76(4e) C0,Me C,H,*N02-4 0 124-126 EtOH 64 I?:) CHO Ph NPh 141-142 EtOH 60(4f)' CN C,Hb*NO,-4 0 116-116 EtOH 70a L. Balbiano, Gazzetta., 1898, 28, 385. J . D. Kendall andc T. G. Duffin, B.P. 797,144 (Chem. Abs., 1969, 53, 4984).Sasaki and T. Yoshioka, Bull. Chem. SOC.Japan, 1968, 2212.SCHEME 1The main difference between this reaction and thecorresponding one of the carbonyl-stabilised ylides withthe same 1,3-dipoles is that, in our case, the formationof the five membered heterocycles is accompanied byelimination of a triphenylmethylphosphonium salt.Our results can be explained in terms of electrophilicattack of the dipole at the y-carbon atom of the ylide.In this case the positions involved in the formation ofthe cycloadduct are the p and the y, without involve-ment, as in the case of simple carbonyl ylides, of thec=o group.* W. J. Bailey and J. Bello, J . Org. Chem., 1955, 20, 626. ' F. Bohlmann and C. Zdero, Chem. Ber., 1973,106, 3779.M. J. Berenguer, J. Castells, J. Fernandez, and R. M.J. R.Neff, R. R. Gruetzmacher, and J. E. Nordlander, J .Galard, Tetrahedron Letters, 1971, 493.Org. Chem., 1974, 39, 3814620 J.C.S. Perkin IThis fact was experimentally confirmed : the reactionof 3-cyanoallylidenetriphenylphosphorane with 4-nitro-benzonitrile oxide in the presence of triethylaminehydrobromide at 0-5 "C afforded [4-cyano-3-(4-nitro-phenyl) -A2-isoxazolin-5-ylmet h yl] triphenylphosphoniumbromide (6).* On heating with triethylamine inmethanol, a nearly quantitative yield of (4f) was obtained(Scheme 2).The ready elimination of triphen ylmethylphosphoniumbromide from (6) occurs through a carbanion mechanism,driven by the resulting gain in aromaticity.EXPERIMENTALN.m.r. spectra were measured with a Varian A-60spectrometer (solvent CDC1, ; Me,Si as internal standard).NC-CW NC-CH-I+ i - * II Ph3P-CH Ph,P-CHCHIICH 4e--)General Procedure f o r the Preparation of HeterocyclicDevivatives.-A mixture of the ylide (0.01 mol), the hydr-azonyl halide or nitrile oxide (0.01 mol), and triethylamine(0.01 mol) in methanol (50 ml) was kept at room temperaturefor 2 h and then refluxed for 2 h.The solvent was evapor-ated off and the residue taken up in benzene (75 ml) andwater (25 ml). From the organic solution the heterocycliccom9ounds (4a-f) were obtained by conventional work-up.Addition of aqueous 60% perchloric acid (2 ml) to theaqueous layer gave triphenylphosphonium perchlorate,m.p. 164" (from methanol).[4-Cyano-3- (4-nitropJzeny1) -A2-isoxazolin-5-yletJzy~,?ri-Phenylphosphoniuun Bromide (6) .-To a stirred solution of3-cyanoallylidenetriphenylphosphorane (3.27 g) in chloro-form (50 ml) cooled to 0 "C were added 4-nitrobenzonitrileoxide ( 1.64 g) and triethylamine hydrobromide ( 1.8 1 g) .The mixture was set aside for 2 h and evaporated in vacuo.+C-C,Hi N02-4 NC- H C -C-CsH, N02--4 +I 4 1 II- / ,!C\oP0 Ph, P-CH, Bf-(6)SCHEME 2Elemental analyses for new compounds are available asSupplementary Publication No.SUP 21651 (2 pp.).?3-Cyanoallyltriphenylj1hosphoniuun Bromide ( 1) .-Tri-phenylphosphine (26.2 g) and 4-bromocrotononitrile 13 (14.6g) in acetonitrile (70 ml) were left a t room temperature over-night. The precipitate was filtered off and recrystallizedfrom ethanol; yield 34.5 g (85%); m.p. 213".3-CyanoallylidenetriphenylpJ~osphmalze.-The salt (1) (8.16g) in water (100 ml) was treated with N-sodium hydroxide(20 ml) and the product was filtered off; yield 5.9 g (90%) ;m.p. 164" (from benzene).* Owing to the lack of solubility of this compound, poor lHn.m.r. spectra were obtained from which only qualitative in-ferences could be drawn.Et 3N * 65'CThe residue was recrystallized from methanol; yield 2.86 g(50%); m.p. 220".4-Cyano-3-(4-nitropJzenyl)isoxazole (4f) .-A solution ofcompound (6) (1 g) in methanol (25 ml) was treated withtriethylamine (0.5 ml) and refluxed for 2 h. The solventwas evaporated off and the product (4f) (0.32 g, 85%) wasobtained from the residue as described above for thepreparation of heterocyclic derivatives.We thank the Consiglio Nazionale delle Ricerche, Rome,[Fill424 Received, 18th July, 19751for financial support.t For details of Supplementary Publications see Notice toAuthors No. 7, J.C.S. Perkin I, 1975, Index issue
展开▼
