2030 J.C.S. Perkin ICondensed Thiophen Ring Systems. Part 1X.l Synthesis and Some Re-actions of I Benzothieno3,2-ccinnolinesBy K. E. Chippendale, 6. Iddon," and H. Suschitzky, Department of Chemistry and Applied Chemistry,I Benzothieno3,2-~cinnoline (1 ) and some of its derivatives are obtained (55-75 yields) when aqueoussolutions of the diazonium chlorides derived from 2- (o-aminophenyl) benzobthiophens are kept a t room tempera-ture. A number of reactions of compound (1) are reported.University of Salford, Salford M5 4WTIN Part VIII1 we reported the synthesis of 2-(o-azido-phenyl)benzobthiophen through diazotisation of 2-(0-aminophenyl)benzobthiophen and treatment of thediazonium compound with sodium azide a t 0". A by-product of this reaction was the hitherto unknownheterocycle, lbenzothieno3,2-~cinnoline (1) , whicharises by a Widman-Stoenner-type cyclisation of thediazonium compound.2 We have found that a highyield (75) of compound (1) is obtained when anaqueous solution of the diazonium compound is kept a troom temperature. Ring-closure on to the thiophenring is due to the resonance contributor (4), and isanalogous to the recently reported3 synthesis of 2-Part VIII, K.E. Chippendale, B. Iddon, and H. Suschitzky,preceding paper.J. C. E. Simpson, 'Condensed Pyridazine and PyrazineRings,' ed. A. Weissberger, Interscience, New York, 1953,Part I, pp. 3-65.methoxybenzoccinnoline (5), where the methoxy-groupprovides the necessary activation for cyclisation.Thereaction which we now report can be extended, forexample to prepare 8-methyl- (2) and 8-chloro-lbenzo-thieno3,2-ccinnoline (3).lBenzothieno3,2-~cinnoline (1) undergoes the ex-pected reactions; for example it is oxidised by peroxy-acetic acid2 to a trioxide. The i.r. spectrum of thiscompound confirms the presence of a sulphone group(vmX. 1155 and 1310 cm-l), but its spectroscopic propertiesdo not indicate the position of N-oxidation. Oxidationwith alkaline potassium permanganate a t 90-95"gave 13 benzothieno3,2-cpyridazine-3,4-dicarboxylicacid (6), a derivative of a new heterocyclic system.(Benzob thiophen is readily oxidised by this reagentJ. S . Swenton, T. J. Ikeler, and B. H. Williams, J. Amer.Chem. SOC.. 1970, 92, 3103.* E. Tauber, Ber., 1895, 28, 4511972 2031system to give o-carboxybenzenesulphonic acid.5) Theisomeric lbenzothieno2,3-dpyridazine (7) and anumber of its derivatives have been reported recently.6When cinnolines are treated with sodium ethoxide inboiling ethanol, ring contraction occurs to give in dole^.^.'t l 1 R = H( 2 ) R = Me( 3 ) R = c1OMe( 5 1( 7 1( 6 1 lBenzothien03,2-~cinnoline (1) similarly gives a lowyield of lOH-lbenzothieno3,2-bindole together withan intractable tar.As expected,B its reaction with ethanolic 1,3-dibromo-propane yields 2,3-dihydrolbenzothieno3,2-cpyrazolo- 1,2-a cinnolinium bromide (8), also a new heterocyclicsystem. 1Benzothieno3,2-ccinnoline (1) dissolves in 20sulphuric acid to give a red-orange solution.Additionof zinc dust decolourises this solution and yields aprecipitate of 5,6-dihydro 11 benzothieno 3,2-c cinnolinesulphate.2 Attempts to isolate this salt failed, however,because it is rapidly aromatised back to (1) in air.Attempts to prepare 3-phenylcinnoline by desulphuris-ation of compound (1) with W-7 Raney nickel inethanol, propan-2-01, or butanol 9~10 were abortive.EXPERIMENTALThe spectroscopic instruments used are described inPart V1II.l Molecular weights were determined by massspectrometry.5-Methyl- 2- (o-nitrophenyl) benzob thiophen and 2- (0-aminophenyl)-5-methylbenzobthiophen were prepared asdescribed in the preceding paper.15-Chloro-2- (0-nitrophenyl) benzo b thiophen (40 yo) wasprepared from 5-chloro-2-benzobthienyl-lithium l1 in ati F.B. Erickson, U.S.P. 2,642,45811953 (Chem. Abs., 1954,48, 5219).M. Robba, G. DorB, and M. Bonhomme, Comfit. rend.,1969, 268C, 256; 1969, 269C, 245; 1970, 271C, 1328; Tetra-hedron, 1972, 28, 2563 (see also 0. Tsuge, s. Iwanami, and s.Hagio, Bull. Chem. Soc. Japan, 1972, 45, 237). ' C . M. Atkinson and J. C . E. Simpson, J - Chem. Soc., 1947,1649.manner similar to that used 1 for 2-(o-nitrophenyl)benzob-thiophen. It had m.p. 111-112" (from ethanol), 't (CDCI,)1-95-2-70 (m, aromatic) Found: C, 58.0; H, 2.8; N,4.5; M , 289; M + 2, 291 (ratio 3 : 1). C,,H,ClNO,Srequires C, 58.0; H, 2.8; N, 4.8; M , 289; M + 2, 291(ratio 3 : l).2-(o-Aminophenyl)-5-chlorobenzo{bthio~hen hydrochloride(82), prepared by reduction 1 of 5-chloro-2-(o-nitrophenyl)-benzobthiophen, had m.p.213-218" (from ethanol),T (Me,SO) 1.75-2.63 (m, aromatic) and 3-80 (exchangeable, + +NH,); vmX. (Nujol) 2560br cm-1 (NH,) (Found: C, 56.5;H, 3.6; N, 4.4. C,4H11Cl,NS requires C, 56.75; H, 3.75;N, 4.7). lBenzothien03,2-~cinnoZine.-A solution of sodiumnitrite (0.56 g, 8.1 mmol) in water (4 ml) was added drop-wise to a stirred mixture of 2-(o-aminophenyl)benzob-thiophen hydrochloride 1 (2.1 g, 7.75 mmol), concentratedhydrochloric acid ( 5 ml), and water (25 ml) a t 0", and theresulting mixture was stirred at 0" for a further 30 min. Itwas then filtered; the filtrate was allowed to warm to roomtemperature, and stirred at this temperature for 90 min.The precipitate was filtered off and crystallised fromethanol to give the product (1.4 g, 75), m.p.212-214",identical with the sample prepared as described previously ;T (CDCl,) 0-95-1.32 (m, 4-H and 7-H) and 1.80-2-45 (m,aromatic); A,, (EtOH) 205 (E 18,780), 237 (35,000), 256(33,560), and 271 nm (21,600); m/e 236 ( M f , 100) and208 (M - N,; m*, 187.6).The following compounds were prepared similarly :S-methyZ lbenzothieno3,2-~cinnoline (56), m.p. 222-224"(from ethanol), T (CDCl,) 1-05-1-34 (m, 4-H and 7-H),1.85-2-73 (m, aromatic), and 7-38 (CH,) (Found: C, 71.7;H, 4-1; N, 11.2; M , 250. Cl,H1,N2S requires C, 72.0;H, 4.0; N, 11.2 ; M , 250) ; 8-chZorolbenzothieno3,2-c-cinnoline (55), m.p. 261-263" (from ethyl acetate),T (CF,*CO,D) 1-08-2.00 (m, aromatic) Found: C, 61-9;H, 2-7; N, 10.4; M , 270; M + 2, 272 (ratio 3 : 1).Cl,H,ClN2S requires C, 62-1; H, 2.6; N, 10-30/,; M , 270;M + 2, 272 (ratio 3 : l).Reactions of 1Benzothieno3,2-ccinnolzne.-(a) Oxid-ation. (i) Hydrogen peroxide (100 vols; 8 ml) was addeddropwise to a stirred mixture of lbenzothieno3,2-c-cinnoline (0-8 g, 3-39 mmol) in acetic acid (8 ml) a t roomtemperature, and the resulting mixture was then heated at90-95" for 2 h.It was cooled and the precipitate wasfiltered off to give lbenzothieno3,2-~cinnoline 5(6), 11,ll-trioxide (0-8 g, say0), m.p. 264-266' (from ethanol), vmX.(Nujol) 1155s and 1310s cm-l (SO,); T (Me2SO) 0.84-1-18(q, Jo 8-0, Jm 2.0 Hz, 4-H or 7-H) and 1.20-2.00 (m,aromatic) (Found: C, 58.6; H, 3.1; N, 9.5.Cl,H,N,O,Srequires C, 59-15; H, 2.8; N, 9.8).(ii) A solution of potassium permanganate (8-0 g, 50.6mmol) and potassium hydroxide (0-5 g, 9.0 mmol) in water(100 ml) was added slowly t o a stirred mixture of llbenzo-thieno3,2-ccinnoline (1.0 g, 4-24 mmol) and water (25 ml)heated on a steam-bath, and the resulting mixture washeated on the steam-bath for a further 3 h. It was thenfiltered and the volume of the filtrate was reduced to 50 ml.Acidification of the residual solution with concentratedD. G. Farnum, R. J. Alaimo, and J. ill. Dunston, J . Org.Chem., 1967, 32, 1130.D. E. Boswell, J. A. Brennan, P. S. Landis, and P. G.Rodewald, J . Heterocyclic Chem., 1968, 5, 69.lo B.Iddon and R. M. Scrowston, Adv. Heterocyclic Chew.,1970, 11, 375.l1 R. P. Dickinson and B. Iddon, J . Chem. SOC. (C), 1971. 1822032 J.C.S. Perkin Ihydrochloric acid gave 11 benzothieno3,2-cpyridazine-3,4-dicarboxyzic acid (0-4 g, 35.5), m.p. 203-265" (fromaqueous ethanol), vmx. (Nujol) 3300br (OH) and 1700s cm-1(CO) (Found: C, 52.95; H, 2.5; N, 10.2; M , 274.C,,H,N,O,S requires C, 52.5; H, 2-2; N, 10.2; M , 274).To a solution of llbenzothieno-3,2-ccinnoline (1.0 g, 4.24 mmol) in ethanol (40 ml) heatedunder reflux sodium (3.5 g, 0-15 g atom) was added piece bypiece (0.2-0-4 g). The resulting mixture was heatedunder reflux for a further 3 h, then cooled and poured intowater (10 ml). Continuous extraction of the resultingaqueous solution for 24 h with chloroform gave a tar whichwas chromatographed on alumina.Ether eluted startingmaterial (0.5 g, 50), m.p. 212-214" (from ethanol), andchloroform eluted 1023- lbenzothieno3,2-bindole (0-1 g,21 based on conversion), m.p. 250-252' (from benzene),identical with an authentic samp1e.l(b) Ring contraction.(c) With 1,3-dibromopropane. A solution of llbenzo-thieno3,2-~cinnoline (1.0 g, 4-24 mmol) and 1,3-dibromo-propane (4.6 g, 22.8 mmol) in ethanol (60 ml) was heatedunder reflux for 100 h. Distillation of the solvent underreduced pressure gave a residue which was crystallisedfrom ethanol, to give 2,3-dihyd~o lbenzothieno3,2-c-~yrazoZo1,2-acinnoZinium bromide (0.4 g, 26.5), m.p.223-229" (decornp.) (Found: C, 56.65; H, 3.6.C,,H,,BrN,S requires C, 57.1; H, 3.7).We thank the S.R.C. for financial support (C.A.P.S. toK. E. C.), Dr. J . W. James and his colleagues at the NicholasResearch Institute for providing the facilities to carry outthis work during an industrial visit (by K. E. C . ) , and Dr.R. P. Dickinson for a sample of 5-~hlorobenzobthiophen.2/670 Received, 21st March, 1972
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