Heterocycles by cycloaddition. Part I. Cycloadditionndash;extrusionndash;ring expansion reactions of five-membered mesoionic compounds with diphenylcyclopropenone and related compounds: preparation of six-membered heterocycles

摘要

632 J.C.S. Perkin IHeterocycles by Cycloaddition. Part 1. Cycloaddition-Extrusion-RingExpansion Reactions of Five-membered Mesoionic Compounds withDiphenylcyclopropenone and Related Compounds : Preparation of Six-membered HeterocyclesBy Hiroshi Matsukubo and Hiroshi Kato,' Department of Chemistry, Faculty of Science, Shinshu University,Cycloaddition-extrusion-ring expansion reactions of mesoionic oxazolones (9) and a thiazolone (1 5) with2.3-diphenylcyclopropenylidene compounds (1 0) gave pyridin-4-one, -thione, and -imine, and 4-methylene-dihydropyridine derivatives (1 2). The reactions of a mesoionic dithiolone (1 7) with cyclopropenylidene derivativesmainly gave thiopyranone and 4-methylenethiopyran derivatives (1 9).Asahi, Matsumoto 390, JapanTHE cycloadduct (2) formed by the reaction of a five-membered mesoionic compound (1) with a dipolarophilicolefin generally fragments further under the reaction con-ditions to give a 1,3-dipolar intermediate (3), whichultimately gives a five-membered heterocycle (6) bymigration of a substituent.l In a few cases, the 1,3-dipole (3) reacts further with the olefin to give a bridgedbis-adduct (7) .2$3In the case of the reaction of a mesoionic compoundwith a strained dipolarophile, a third reaction route maybe envisaged, in which fragmentation of the initial adduct(4) may be accompanied by simultaneous cleavage of thestrained bond to afford a ring-enlarged product (5) asshown in Scheme 1.In this Scheme, a, b, d, e, and X of//12c:cR2the ring system (1) may be any atoms or groups whichsatisfy the definition of mesoionic compound,4 and Y maybe any atom or group which provides sufficient energy inthe resulting ring.This route has been realised recentlyby Martin and H e k m a ~ ~ , ~ who showed that the reactionsof a mesoionic oxazol-5-one with cyclopropene and cyclo-butene give the corresponding six- and seven-memberedheterocycles.We describe here the cycloaddition-extrusion reactionsof some five-membered mesoionic compounds with 2,3-M. Ohta and H. Kato, ' Nonbenzenoid Aromatics,' vol. 1,ed. J. P. Snyder, Academic Press, New York, 1969, p. 117.H. Gotthardt and R. Huisgen, Chem. Be?., 1970, 103, 2626.This reaction actually gives the endo,exo-bis-adduct (m,p. 212-214") in addition to the exo,exo-bis-adduct reported by Gotthardtand Huisgen (H.Kato and K. Morisaki, unpublished data).P. M. Weintraub, Chem. Comm., 1970, 760. * W. Baker and W. D. Ollis, Quart. Rev., 1957,11, 15.diphenylcyclopropen-one, -thione, and -imine, and 3-meth ylenecyclopropene derivatives (hereafter referredto as cyclopropenylidene derivatives) .'j We hoped thatthese reactions would serve as a convenient procedure forthe preparation of fully conjugated six-membered hetero-cycles. Further, the reactions have an added interest inview of the ability of cyclopropenylidene derivatives toundergo cycloaddition reactions across the 1,2- or the2,3-position or across the exocyclic double bond depend-ing on the nature of the other reagent, and the fact thatdiphenylcyclopropenone acts, in some cases, only as amasked diphenylacetylene.' During the present in-vestigation, Potts and Baum independently reportedreactions of the same type; their results partly overlapwith ours.The mesoionic 3-methyl-2,4-diplienyloxazol-5-one (9a) ,prepared in sitzc from 2- (N-met hylbenzamido) -2-phenyl-acetic acid (8a) ,2 reacted readily with diphenylcyclopro-penone (loa) to give l-methyl-2,3,5,6-tetraphenyl-4(1H)-pyridone (12a).The assigned structure (12a) was sup-ported by spectral data [.,. 1612 cm-l (CO) ; 6 7.03 and7.18 (each 10H, s)], which eliminate the isomeric 2- and 3-pyridone structures, and confirmed by comparison with asample prepared by the reaction of 1,2,4,5-tetraphenyl-pentane-1,3,5-trione (13) with methylamine. Similar i i tsitu reactions of the oxazolone (9a) with diphenylcyclo-propenethione (lob) and tosylimino- (1Oc) , dicyano-methylene- (lOd), and cyano(ethoxycarbony1)methylene-diphenylcyclopropene (10e) gave the corresponding di-hydropyridine derivatives (12b-e) in acceptable yields(see Table).The structures of the dihydropyridines(12b-e) were supported by spectral data and in somecases by comparison with samples synthesised via differentroutes. The reaction of the pyridone (12a) with phos-phorus pentasulphide gave the pyridinethione (12b).Treatment of the pyridone (12a) with triethyloxoniumfluoroborate gave 4-ethoxy-l-methy1-2,3,5,6-tetraphenyl-pyridinium fluoroborate (14), which was then treatedwith toluene-$-sulphonamide or malononitrile in thepresence of base to give the corresponding tosylimino-(12c) or dicyanomethylene (12d) derivative.5 H.-D.Martin and M. Hekman, Angew. Chem. Iitternat. Edn.,6 Preliminary report, H. Matsukubo and H. Kato, J.C.S. Clieiii.7 I. T. Potts and J. S. Baum, Chem. Rev., 1974, 74, 189;8 I. T. Potts and J . Baum, J.C.S. Cizem. Comm., 1073. 833.1972, 11, 926.Comm., 1974, 676.M. L. Deem, Synthesis, 1972, 6751975 633(8)a; Ar=Phb; Ar =p-NOiC6H1X(91 (101 (1 1) (12)a ; X = O a; Ar=Ph,X=O b; Ar =Ph, X= Sb j X = S c; Ar = Ph,X=NTs d;Ar=Ph,X=C(CNhe; Ar = Ph, X=C(CN).C02Et c ; X=NTsd ; X =C(CNhe ; X =C(CN)*C02Etf ; Ar=p-NOiC6HL,X=0CJ; Ar =p-NOi C6H&, X=Sh ; Af = p - NOIC~HL ,X=CICNl;!OEt ...I l lPhCO.CHPh.CO.CHPh.COPh - (12al ____cIMe I (13) lv (12 bl (12d (12dlSCHEME 2 Reagents: i, Ac,O; ii, hIeNH,; iii, Et,O+BF,-; iv, Paslo; v, TsNH,NaOBut ; vi, CH,(CN),-NaOButSimilar in situ reactions of the mesoionic 3-methyl-2-9-nitrophenyl-4-phenyloxazol-5-one (9b) with the diphenyl-cyclopropenylidene derivatives (10a, b, and d) gave thecorresponding 2-9-nitrophenylpyridine derivatives (12f,g, and h). This oxazolone (9b) is relatively stable, andit is possible to use it in isolated form.g The yield of(12g), however, was not improved by use of the isolated T h y - :oxazolone (9b).These results show that the cycloaddition reactions ofmesoionic compounds with cyclopropenylidene deriva-tives (10) took place as expected to give the initial cyclo-The pyridine derivatives (12a-e) could also be pre- /*pared in- comparable yields by the reactions of cyclo-propenylidene derivatives (10a-e) with the mesoionic 3-methyl-2,4-diphenylthiazol-5-one (15) lo in refluxingxylene.Lastly, the reactions of the mesoionic 2,5-diphenyl-l,3-dithiol-4-one (17) l1 with diphenylcyclopropenone (10a)and dicyanomethylenediphenylcyclopropene (10d) inxylene under reflux afforded 2,3,5,6-tetraphenylthio-pyran-4-one (19a) l2 and the 4-dicyanomethylene- (171 (18) 'analogue (19b), respectively, though in relatively lowyields.In the case of the reaction of the dithiolone (17) with(loe), another product was formed (16%) in addition tothat expected (19c).The by-product retained a cyano-and the n.m.r.spectrum showed only a complex aromaticproton signal. From these spectral data and the com-bustion and mass analyses, the indeno[l,e-c] thiopyran(15) (161Ph(20)SCHEME 3substituent but no longer showed an i.r. carbonyl band,XPh(191a; X=Ob; X=C(CN)2c; X=C(CN)C02Etadducts (1 1), (16), and (18), which underwent fragment-sulphide accompanied by cleavage of the t hree-memberedl1 H. Gotthardt and B. Christl, Tetrahedron Letters, 1968, 4743.l2 K. W. Hubel and E. H. Braye, U.S.P., 3,280,017 (Chem.structure (20) was assigned.ful.Clzem. Bey., 1970, 103, 2581.E. Brunn, Tetrahedron Letters, 1967, 1809.Attempts at converting(lgC) into (20) PYrolYsis were not success- ation with extrusion of carbon dioxide or carbon oxy-H.0. Bayer, R. Huisgen, R. Knorr, and F. C. Schaefer,lo R. Huisgen, E. Funke, F. C. Schaefer, H. Gotthardt, andAbs., 1967, 66, 2462)J.C.S. Perkin Iring to give the fully conjugated six-membered hetero-cycles. The cycloaddition of the five-membered meso-ionic compounds always occurred across the 2,3-doublebond of the cyclopropenylidene derivatives irrespectiveof the nature of the exocyclic multiple bond and of thenature of the mesoionic ring system. In this sense, thebehaviour of the cyclopropenylidene derivatives (10)towards mesoionic 1,3-dipoles is in strong contrast withthat towards open-chain 1,3-dipoles, which showquite versatile behaviour depending upon the nature ofthe constituent heteroatoms.6*7J3It may appear that the reactions of this type afford anattractive method for the preparation of a wide variety ofpounds (12), (19), and (20) are available as Supple-mentary Publication No.SUP 21248 (3 pp.).EXPERIMENTALUnless otherwise stated, n1.p.s were determined on aYanagimoto hot-stage apparatus. U.V. and i.r. (KBr)spectra were recorded on Hitachi EPS-3T and EPI-G3spectrophotometers. h'.m.r. spectra were obtained on aJEOL JNM-4H-100 (100 MHz) spectrometer for solutionsin deuteriochloroform (standard internal tetramethylsilane) .Mass spectra were measured with a Hitachi RMU-6 spectro-meter at 70 eV (direct inlet technique). Compounds statedto be identical were so on the basis of m.p., mixed m.p., andi.r. and n.m.r. spectral determinations.TABLE 1Preparation and properties of cycloadductsProcedurePro - I-- -l duct Reactants T/"Ca t/h Isolation66Rfl66Rfl60Rfl80Rfl80Rfl8080RflRflRflRflRflRfl17.617.611658153.682.5910111616B (Me,CO)AAAB (Et,O):, (ET"COAC1,)AB (Me,CO)AB (PhH)B (PhH, Et,O)AB (PhH)AAC (PhH)C (PhH)(%I61656148643941746573535244623819816Analyses (%) t(Recryst. solvent) ( "C) Formula C H NYield Appearance M.p.d -7Needles(Me,NCHO)Yellow prisms(Me,N*CHO)PlatesYellow prisms(Me,NCHO)Orange prismsPale yellow prismsOrange-yellow prismsYellow needlesPale yellow prisms(Xylene)Yellow prismsYellow prisms(EtOH)Orange needles(CH,Cl,-Et,O)( CH,C1,-EtzO)(CH,Cl,-EtzO)( CH,ClS-E t SO)(CH,Cl,-Et,O)(CHtClz-EtZO)(MezCO)313-316 '341-342* f(decomp.)360-361 *(decornp.)(decornp.)3 10.5-31 2.6307.6-309 g281-282307-309 330318.5-319'305.Ei-306.6186.6- 1 8 7.5296-296.6C,,H,,NO 86.6 6-66 3-36(87.15) (5.6) (3-4)C,,H,,NS 83.75 6.46 3.0(83.9) (6.4) (3-26)C3,H30N20,S 77.96 6.3 4.9(78.4) (6.35) (4-96)C33Hz3N3 85.0 6.0 9.2(86.86) (6.0) (9.1)C,,H,,N,O, 82.3 6-66 5.7(82.66) (6.66) (5.5)C30H,,N,03 78.86 5.1 6-16(78.6) (4.86) (6-1)C30H,,N,0,S 76.7 4.6 6.9(76.96) (4.66) (6-9)C3,H,,N40, 78.16 4.4 11.36(78.26) (4.4) (11.06)(83.6) (4.86)(82.76) (4.36) (6-06)(79.8) (4.96) (2.76)(86.1) (4.4) (3.2)C,QH,oOS 83-26 4.76C3,H,,N,S 82.6 4.36 5.76C3,H,,NOzS 79.86 6.1 2.7C,,H,QNS 84.8 4.26 3.06a Rfl: reflux.b Isolation procedures: '4, crystals which separated on cooling were collected; B, solvent was distilled off and theresidue triturated with the solvent shown in the parentheses; C, products were separated by column chromatography on silica gelwith the eluant shown in parentheses. 0 Yields based on purified products. M.p.s. with an asterisk were determined in a capillarytube. Lit.,' 309-310". f Lit.,' 320-322" (decornp.). g liesolidified a t 313-315". Lit.,', 319-320".t Required values in parentheses. Some compounds gave consistently low carbon values but their purity was supported byspectral data and t.1.c. Mass spectra of all compounds gave consistent molecular ion peaks.fully conjugated six-membered heterocycles.However,the success of this method actually depends on the re-activity of the mesoionic ring system : the reactions of themesoionic oxazolone (9) proceed readily at moderatetemperature, but those of the mesoionic thiazolone (15)and dithiolone (17) require a long reaction time and arelatively high temperature. Further, with some othermesoionic ring systems, the expected cycloaddition-extrusion-ring expansion products were not obtained.Either the starting material was unchanged or a complexproduct mixture resulted from the reactions of diphenyl-cyclopropenone (10a) with 3-phenylsydnone, mesoionic4-phenyl- 1 ,3,2-oxat hiazol-&one, and mesoionic 2,3,5-triphenylthiazol-4-one ; and cyclopropenethione (lob)did not react with the dithiolone (17).The U.V. andn.m.r. spectra and pertinent i.r. and mass spectra of com-l3 H. Matsukubo and H. Kato, unpublished data.Cycloaddition Reactions of DiphenylcyclopropenylideneDerivatives (10) and Mesoionic Oxazolones (9) prepared insitu. General Procedure.-Under nitrogen, a solution of 2-(N-methylaroylamino)-2-phenylacetic acid (8) (0.3-0.55 g)in freshly distilled acetic anhydride ( 5 ml) was warmed at 55"for 5 min. An equivalent amount of cyclopropenylidenederivative (10) was then added, the resulting solution orsuspension was warmed, and the products were isolated byappropriate procedures. The results are listed in the Table.Cycloaddition Reactions of DiphenylcyclopropenylideneDerivatives ( 10) and Mesoionic Compounds ( 15) and ( 17).General Procedure.-A solution or suspension of the mesoioniccompound (0.2-0.5 g) and an equimolar amount of di-phenylcyclopropenylidene derivative (10) in xylene (5-1 0ml) was refluxed, and the products were isolated by suitablemethods. The results are shown in the Table.l-Methyl-2,3,5,6-tetraphenyl-4( lH)-pyridone (12a) .-Asolution of 1,2,4,5-tetraphenylpentane-1,3,5-trione (0.31 g)and ethanolic 30% methylamine (0.5 ml) in ethanol (50 ml1975 635was kept overnight at room temperature.More ethanolicmethylamine (0.5 ml) was added, and the solution was re-fluxed for 5.5 h. The solvent was distilled off and the resi-due was recrystallised from dimethylformamide to giveprisnis (l2a) (0.13 g, 43y0), m.p. 307-308.5", identical withthe sample prepared by cycloaddition.l-MethyZ-2,3,5,6-tetraphenyZpyridine-4( 1H)-thione ( 12b) .-The pyridone ( 12a) (0- 1 g) and phosphorus pentasulphide(0.08 g) in xylene (50 ml) were refluxed for 6 h.The organicsolution was concentrated and the residue was recrystallisedfrom dimethylformamide to give the pyridinethione ( 12b)(0.05 g, 48y0), identical with the specimen prepared bycycloacldition.4-Ethoxy- l-methyZ-2,3,5,6-telvapC~enyZ~yridiniul.12 Fluoro-borate (14) .-To a solution of triethyloxonium fluoroborate( 5 g) in dichloromethane (10 ml) was added a solution ofpyridone (12a) (1 g) in dichloromethane (15 ml). Afterstirring for 2 h, the solution was concentrated and theprecipitate was recrystallised from ethanol to give thefluoroborate (14) (1.27 g, 99%) as needles, m.p.268-273"(decomp.) (lit.,? 275-278"). This crude material was usedwithout further purification. The u.v., i.r., and n.m.r.spectra agreed with those reported.?Pyridine (12c) .-A mixture of ethoxypyridinium fluoro-1 , 4-Dihydro- l-methyZ-2,3,5,6-tetra~henyZ-4-tosyZimino-borate (14) (0.1 g), toluene-p-sulphonamide (0.07 g), sodiumt-butoxide [from sodium (0.01 g ) ] , and t-butyl alcohol (12ml) was refluxed for 3 h. The mixture was concentrated invamo and the residue was recrystallised from dichloro-methane-ether to give the tosyliminopyridine (12c) (0.09 g,84%), m.p. 310-312.5", identical with the sample preparedby cycloaddition; A,. (MeOH) 324 nm (log E 4.112); vmax1586 cm-l (CN) ; 6 7.35-7-02 (22H, m), 6-73 (2H, d, J 8 Hz),3.14 (3H, s), and 2.19 (3H, s); m/e 566 (7%), 411 (81), and397 (100).4-Dicyanornethylene- 1,4-dihydro- l-methyZ-2,3,5,6-tetra-phenylpyridine ( 12d) .-The pyridinium fluoroborate (14)(0.1 g) was treated with malononitrile (0.025 g) by essentiallythe same procedure as described above to give the dicyano-methylenedihydropyridine (1 2d) (0.07 g, 80%) , identicalwith the sample prepared by cycloaddition; A,, (MeOH)246 (log E 4.309) and 383 nm (4.499) ; v,, 2180, 2155 (CiN),and 1584 cm-l ( C X ) ; 6 7.14br (lOH, s), 7.06br (lOH, s), and2-98 (3H, s); m/e 461 (looyo), 460 (81), and 118 (9).We are indebted to Kyorin Chemical Laboratories forelemental analyses and mass spectra, and to Mr. NaomiTakagi for experimental assistance.[4/2040 Received, 4th Octobev, 1974