Triazines and related products. Part 18. Decomposition of 1,2,3-benzotriazines and related triazenes with sodium azide in acetic acid: a convenient route to azidoarenes

摘要

1977 103Triazines and Related Products. Part 182 Decomposition of 1,2,3-Benzotriazines and Related Triazenes with Sodium Azide in Acetic Acid :a Convenient Route to AzidoarenesBy Andreas Gescher, Malcolm F. G. Stevens," and Colin P. Turnbull, Department of Pharmacy, Universityof Aston in Birmingham, Birmingham B4 7ET1.2,3-Benzotriazin-4(3H) -one and its 3-aryl derivatives decompose in boiling acetic acid containing sodium azideor sodium iodide to afford 2-azido- and 2-iodo-benzamides, respectively, in high yields. Certain azidoarenes withnucleophilic orrho-substituents, formed from the decomposition of 1,2,3- benzotriazines and related aryltriazenes,cyclise with elimination of nitrogen under the reaction conditions. 1.2-Bis-o-nitrophenyltriazene in acetic acidcontaining sodium azide yields benzofurazan N-oxide and 2-nitroaniline.WE have previously described the degradation of 1,2,3-benzotriazin4(3H)-ones (1) in the presence of secondaryamines and reactive methylene systems.3 3-Alkyl-,3-aryl-, and 3-aralkyl-l,2,3-benzotriazin-4(3H)-ones are,in general, unreactive towards amine nucleophiles,whereas the parent triazinone (la) undergoes nucleo-philic attack at C-4 with subsequent ring opening andloss of nitrogen to afford anthranilamide derivative^.^^^We anticipated that a similar nucleophilic attack byazide ion could lead to the triazenobenzoyl azide (2),which should undergo successive losses of nitrogen first togive anthraniloyl azide (3) and thence, via a Curtiusrearrangement ,5 benzimidazolone (4) (Scheme).The triazinone (la) however was recovered unchangedfrom boiling aqueous ethanol, dimethylformamide, ordimethyl sulphoxide containing an excess of sodium1 Part 17, E.J. Gray, M. F. G. Stevens, G. Tennant, andR. J . S. Vevers, J.C.S. Perkin I , 1976, 1496.2 M. S. S. Siddiqui and M. F. G. Stevens, J.C.S. Perkin I , 1974,611.3 M. S. S. Siddiqui and M. F. G. Stevens, J.C.S. Perkin I , 1974,2482.A. W. Murray and K. Vaughan, J . Chem. SOG. ( C ) , 1970,2070.azide. Boiling acetic acid, which is known to be an idealsolvent to promote reversible ring-opening of 1,2,3-benzo-triazin-4(3H)-ones (1) to -the diazonium species (5),s-*proved an admirable medium for azide-promoted decom-position, and the unsubstituted triazinone (la) wassmoothly converted in near quantitative yield into 2-azidobenzamide (6a) and not the predicted product.Al-though 3-alkyl- and S-aralkyl-l,2,3-benzotriazin-4(3H)-ones (1 b-h) were unchanged under the same conditions,high yields of N-aryl-2-azidobenzamides (6i-1) wereobtained from the corresponding 3-aryltriazinones (li-1) :the difference in reactivity may be attributed to theelectronic influence of the aryl substituents which inthese cases encourage initial heterolysis of the triazinoneN(2)-N(3) bond.3 Similar features explain the successfulconversion of the 3-pyrimidinyltriazinone (lm) into theappropriate azide (6m). This procedure represents aM. S. Gibson and M. Green, Tetrahedron, 1966, 21, 2191.J. G. Erickson, ' The Chemistry of Heterocyclic Compounds,'ed.A. Weissberger, Interscience, New York, vy1. 10, p. 1.J. P. Horwitz, ' Heterocyclic Compounds, ed. R. C. Elder-field, Wiley, New York, 1961, vol. 7, p. 778. * A. C. Mair and M. F. G. Stevens, J . Chem. SOG. (C), 1971,2317104 J.C.S. Perkin Iuseful new synthesis of N-aryl-2-azidobenzamides, which,unlike the N-alkyl and N-aralkyl analogues, cannot beprepared from appropriately substituted anthranil-amides by the usual diazotisation-azidation route becauseof the dominating competitive intramolecular cyclis-at ion to 3-aryl- 1,2,3- benzo t riazin-4 (3H) -ones .8$The unsubstituted triazinone (la) and its N-aryl deriv-atives (li and 1) also decomposed in acetic acid containingHf i c o . N H R( 7 )a ; R = Hb ; R = M eC ; R = E td ; R = Prne ; R = P r 'f ; R = CCH23,.OHg ; R = PhCH2h i R = PhCCH272i ; R = P hj ; R = o - M e C amp; t ~k ; R =o-NOz'CgHLI ; R=p-NO*.CbH'SCHEME Reagents : i, AcOH; ii, NaN,-AcOH ; iii, NaI-AcOHsodium iodide to afford high yields of the corresponding2-iodobenzamides (7a, i, and 1) respectively, but all theN-alkyltriazinones (lb-h) failed to react under thesame conditions.The nucleophilicity of the partici-pating anion also limits the synthetic scope of the de-T. B. Brown and M. F. G. Stevens, J . C . S . Perkin I, 1976,1023.lo H. N. E. Stevens and M. F. G. Stevens, J. Chem. SOC. ( C ) ,1970, 2308.composition: no 2-substituted benzamides were isolatedwhen the triazinone (la) was boiled in acetic acid(10)containing sodium bromide, chloride, cyanide, acetate,or sulphite.Conceivably more strongly nucleophilicanions would be as effective as azide and iodide ions.Decomposition of benzimidazol,2-c 1,2,3benzo-triazine (8) in acetic acid-sodium azide yielded the known2-o-azidophenylbenzimidazole (9), which was furthercharacterised by thennolytic cyclisation at 200 "C to theindazolo2,3-a benzimidazole (10) .lo In contrast , thes-triazinol,2-c 1,2,3benzotriazines (1 la-c) were trans-formed into the corresponding diamino-s-triazinol,2-b-indazoles (13a-c) in acetic acid-sodium azide. Theintermediates in these reactions the o-azidophenyl-s-triazines (12a-c) were shown independently to cyclisein boiling acetic acid, probably by a facilitated neigh-bouring-group elimination of nitrogen.llNH(11) (121(13)a ; R = Hb ; R = M ec ; R = B rThe acyclic NNN-systems (triazenes) also decomposedsmoothly under the influence of azide ion, particularlywith those substrates bearing an ortko-substituent suit-l1 s.M. Mackenzie and M. F. G. Stevens, J. Chem. SOC. ( C ) ,1970, 22981977 105able to interact with the azide group. For example,4-amino-2-2- (piperidin-1-ylazo) phenyllquinazoline (14)yielded the corresponding azide (15) after a short time inboiling acetic acid; prolonged reaction led to the form-ation of a mixture of the isomeric aminoindazoloquin-azolines (16) and (17). The azide (19) formed from thecorresponding quinazolone (18) showed no tendency tonitrophenyl azide in boiling acetic acid.On the otherhand, decomposition of the isomeric 1,3-bis-o-nitrophenyl-triazene (20) on a preparative scale gave only benzo-furazan N-oxide (22) and 2-nitroaniline. The benzo-furazan arises from the intermediate 2-nitrophenyl azide(21), which cyclises with nitrogen loss under the reactionconditions.12cyclise, presumably because the more weakly nucleo-philic N-atoms of the quinazolone ring cannot initiate0 0(18) (19)nitrogen loss. Decomposition of the triazene (14) in thepresence of acetic acid-sodium iodide afforded a highyield of the hydroiodide salt of Pamino-2-o-iodophenyl-quinazoline.0-+/(28) +'0-111N(22)Decomposition of 1,3-diaryltriazenes in acetic acid-sodium azide was followed by t.1.c.and in all casesexamined the main products of the reactions were theexpected azido- and amino-arenes. 1 ,S-Bis-fi-chloro-phenyltriazene decomposed smoothly at room temper-ature to afford 4-chlorophenyl azide and 4-chloroaniline.More forcing (boiling) conditions were required with1,3-bis-o-cyanophenyl-l-methyltriazene , which yieldedthe expected 2-azidobenzonitrile and N-methylanthranil-onitrile. Less satisfactory was the degradation of 1,3-bis-P-nitrophenyltriazene, which gave 4-nitrophenyl azideand 4-nitroaniline and at least five other compounds,presumably formed by secondary decomposition of theEXPERIMENTALLight petroleum refers t o the fraction of b.p. 60-80".1.r. spectra were recorded with a Perkin-Elmer 257 spectro-meter for KBr discs.2-Azidobenzumide (6a) .--I ,2,3-Benzotriazin-4( 3H)-one(0.6 g) and sodium azide (4 mol.equiv.) were boiled in aceticacid (5 ml) for 1 h and the mixture was diluted with water.A chloroform extract of the mixture furnished a gum whenconcentrated. Trituration with benzene yielded 2-azido-benzamide (95), which crystallised from benzene as whiteneedles, m.p. 135-136" (lit.,* 135-136") ; vmax. 3 378 and3 170 (NH), 2 140 and 2 110 (NJ, and 1653 cm-l (CO).There was no reaction when the triazinone was boiledwith an excess of sodium azide (4 mol. equiv.) in 75aqueous ethanol, 70 aqueous dimethylformamide, ordimethyl sulphoxide for 3 h.Similarly prepared from the appropriate 3-substituted1,2,3-benzotriazin-4(3H)-ones and sodium azide in boilingacetic acid were the following N-substituted 2-azidobenz-amides; N-phenyl- (64 (95y0), m.p.129-130" (efferv.) asbuff flakes (from aqueous ethanol) (Found: C, 65.6; H,4.0; N, 25.4. C13H1,N40 requires C, 65.5; H, 4.2; N,25;.3), v,, 3 290 (NH), 2 135 and 2 100 (NJ, and 1650cm-1 (CO); N-o-tolyl- (6j) (88), m.p. 100-101", as greyneedles (from ethanol) (Found: C, 66.9; H, 4.6; N, 22.0.C14H,,N,0 requires C, 66.7; H, 4.8; N, 22.2); vmx.3 350 (NH), 2 130 and 2 100 (N3), and 1668 cm-l (CO);N-o-nitrophenyl- (6k) (95), m.p. 150-152" (efferv.) asbronze needles (from ethanol) (Found: C, 54.9; H, 3.0;N, 24.9. C,,H,N,O, requires C, 55.1; H, 3.2; N, 24.7),vmx 3 290 (NH), 2 138 (NJ, and 1 670 cm-l (CO); N-p-nitrophenyl- (61) (93), m.p.162-164" (efferv.) as bronzeneedles (from ethanol) (Found: C, 55.3; H, 3.5; N, 24.7),v, 3 310 (NH), 2 135 (N3), and 1 665 cm-l (CO): N-2-amino-3,4-dilzydro-4-oxo-6-methyl~yrimidi~-5-yl- (6m) (65)m.p. 188-190" (efferv. and .resolid.) as buff micro-rosettes(from ethanol) (Found: C, 50.7; H, 3.6; N, 34.2. C,,H,,-N,O, requires C, 50.5; H, 3.9; N, 34.4), vmx 3 500-2 700 (bonded NH, OH), 2 130 (NJ, and 1 650 cm-l (CO).The 3-alkyltriazinones ( 1 b-f) and 3-aralkyltnazinones(lg and 11) were unchanged by boiling acetic acid containing4 mol. equiv. of sodium azide.l2 P. A. S. Smith and J. H. Boyer, Org. Synth., 1951, 31, 14106 J.C.S. Perkin I2-Iodobenzamide (7a) .-A solution of 1,2,3-benzotriazin-4(3H)-one (1.0 g) in acetic acid (10 ml) containing sodiumiodide (2 mol.equiv.) was boiled (1 h) and diluted with water(20. ml). The precipitated iodobenzamide (85) gavewhte crystals (from aqueous ethanol), m.p. 182-184'(lit.,13 183"), vmx. 3 350 and 3 190 (NH), and 1 640 cm-l (CO).Similarly prepared from the appropriate 3-substituted1,2,3-benzotriazin-4(3H)-ones were the following N-sub-stituted 2-iodobenzamides; N-phenyl- (79 (85), m.p.141-142" (lit.,14 m.p. l42'), v,, 3 230 (NH) and 1 646 cm-1(CO); N-p-nitrophenyl- (71) (goyo), m.p. 213-215O, as paleyellow prisms (from ethanol) (Found: C, 42.6; H, 2.7; N,7.4. C,,H,IN,O, requires C, 42.4; H, 2.5; N, 7.6).2-o-A zidophenylbenzimidazole (9) .-A solution of benz-imidazo1,2-c1,2,3benzotriazine l5 (1.0 g) in acetic acid(10 ml) containing sodium azide (4 mol.equiv.) was boiled(1 h), cooled, and diluted with water (10 ml). The productwas extracted into chloroform, and the extract evaporated.The solid residue, crystallised from light petroleum, yieldedthe azide (85) as brown prisms, m.p. 165-170" (decrep.),identical (i.r. data and thermal behaviour) with an authenticsample.102,4-Diamino-s-triazino lf2-bindazoZe ( 13a) .-(i) kAmino-2-imino-2H-s-triazino 1,2-c 1,2,3benzotriazine l1 ( 1 .O g) ,-acetic acid (10 ml), and sodium azide (4 mol. equiv.) wereboiled (1 h) and the mixture was diluted with water (10 ml).The precipitated triazinoindazole (70) was identical (i.r.and m.p.) with an authentic sample.11(ii) A solution of 2,4-diamino-6-( 2-azidophenyl)-s-triazine11(1.0 g) in acetic acid (10 ml) was boiled (1 h) and dilutedwith water to yield the same triazinoindazole (85).2,4-Diamino-9-methyZ-s-triazino 1,2-bindazoZe ( 13b) .-This triazinoindazole was prepared as above from either4-amino-2-imino- lO-methyl-2H-s-triazino 1,2-c 1,2,3benzo-triazine 11 or 2,4-diamino-6-( 2-azido-5-methylphenyl)-s-tri-azine,ll in 70 or 80 yield, respectively.2,4-Diamino-9-bromo-s-triazino 1,2-bindazole ( 13c) .-Thebromotriazinoindazole was prepared either from 4-amino-1O-bromo-2-imino-2H-s-triazino 1,2-c 1,2,3benzotriazine l1in acetic acid containing sodium azide (78), or from 2,4-diamino-6-( 2-azido-5-bromopheny1)-s-triazine11 (90) inacetic acid alone, and was identical (ix.) with authenticmaterial.11( 15) .-4-Amino-2-2-(piperidin-l-ylazo)phenylquinazoline 16 (1.0 g) was boiledin acetic acid (10 ml) with sodium azide (4 mol.equiv.) for15 min. The mixture was diluted with water and extractedwith chloroform, and the chloroform layer evaporated. Theoily residue was dissolved in benzene and fractionated onan alumina column. The first yellow band, eluted withbenzene, afforded the azidophenyZquinazoZine (27y0), m.p.143-145' (resolid.) (from ethanol) (Found: C, 64.4; H,P A mino-2- (2-azidophenyZ)quinazolinelS W. Wachter, Ber., 1893, 26, 1774.l4 W. Wachter, Ber., 1893, 26, 1744.15 L. L. Zaika and M. M. JouillC, J. Heterocyclic Chem., 1966, 3,444.3.9; N,32.2. C14Hl,N,requiresC, 64.1; H, 3.8; N, 32.1y0),vmx.3 340 and 3 180 (NH), and 2 130 and 2 090 cm-l (NJ.Cyclisation of the azidophenylquinazoline in boiling aceticacid was complete in 1 h. The products, identified as theisomeric indazoloquinazolines ( 16) and (1 7), were recognisedas intensely fluorescent spots on t.1.c. on alumina (0.25 mm)with benzene as developing solvent, with R p identical withthose of authentic samples.l?2-(2-AzidophenyZ)quinazolin-4(3H)-one (19) .-A mixtureof 2-2-(piperidin- l-ylazo)phenylquinazolin-4( 3H)-one 2(1.0 g) and sodium azide (4 mol. equiv.) was boiled in aceticacid (10 ml) for 1 h and diluted with water (10 ml). Theprecipitated quinazolinone (0.5 g) had m.p. 300" (frommethanol) (Found: C, 64.1; H, 3.5; N, 26.3. C14H,N,0requires C, 63.9; H, 3.4; N, 26.6y0), vmX.3 200-2 750(bonded NH, OH), 2 140 and 2 100 (N3), and 1680 cm-l4-Amino-2-( 2-iodophenyl)quinazoline.- 4-Amino-2-2-(piperidin- l-ylazo)phenylquinazoline ( 1.0 g) , sodium iodide(2 mol. equiv.), and acetic acid (10 ml) were boiled (2 h), andthe mixture was diluted with water. The quinazolinecrystallised from ethanol as a hydroiodide salt, m.p. 230"(decomp.) (Found: C, 35.5; H, 2.3; N, 8.7. C14H1,1N3,HIrequires C, 35.4; H, 2.3, N, 8.4). The free base, m.p.191-193" (from ethanol) was formed by basifying thehydroiodide with aqueous ammonia (Found: C, 48.8; H,3.05; I, 36.45; N, 12.4. C14Hl,IN3 requires C, 48.4; H,2.9; I, 36.6; N, 12.1).Decomposition of 1,3-Bis-o-nitro~henyltriazene.-The tri-azene (1.44 g) and sodium azide (1.3 g, 4 mol. equiv.) wereboiled in acetic acid (15 ml) for 1 h after the initial vigorouseffervescence had subsided. Solvent was removed and theresidue triturated with benzene (20 ml) . Sodium acetate(1.7 g) was filtered off and the filtrate fractionated on analumina column (benzene as eluant). The rapidly movingpale yellow band afforded benzofurazan N-oxide (0.55 g)(Slyo), identical (i.r.) with an authentic specimen.12 Thedeep yellow band similarly yielded 2-nitroaniline (0.5 g ,The following 1,3-diaryltriazenes were similarly decom-posed in acetic acid containing sodium azide (4 mol. equiv.).Products (in parentheses) were identified by comparisonwith authentic materials on t.1.c. plates silica gel (0.25 mm) ;benzene-acetone (7 : 3) illuminated at 254 or 366 nm : 1,3-bis-p-chlorophenyltriazene (4-chlorophenyl azide and 4-chloro-aniline) ; 1,3-bis-o-cyanophenyl- 1 -methyltriazene (Z-azido-benzonitrile and N-methylanthranilonitrile) ; 1,3-bis-p-nitrophenyltriazene (4-azidoaniline, 4-nitroaniline, and fiveunidentified products).A. G.) and the S.R.C. for a studentship (to C. P. T.).(CO)83).We thank the Cancer Research Campaign for support (to6/870 Received, 6th May, 1976116 M. F. G. Stevens, J.C.S. Perkin I, 1974, 615.l7 M. F. G. Stevens, J. Chem. SOC. (C), 1967, 1096