192 J.C.S. Perkin ISynthesis and Reactions of 1 H-4,l.Z- Benzothiadiazines, and Observationson the Structure of Hydrazonoyl SulphidesBy Darko J. Vukov, Martin S. Gibson," and (in part) William E. Lee and Mary F. Richardson, DepartmentSyntheses of 1 -acetyl-7- and -8-brorno- and -6,8-dibromo-3-phenyl-4,1.2-benzothiadiazines establish, in con-junction with previous data, the generality of 1 H-4,1,2-benzothiadiazine synthesis from appropriately substitutedN'-acetyl-N'-arylbenzothiohydrazides. The corresponding 6-nitrobenzothiadiazine is also available by this route,and such cyclizations can proceed by expulsion of a nitro-group, presumably as nitrite ion. These 1 H-4,1,2-benzo-thiadiazines undergo electrophilic substitution at positions 6 and 8, are nucleophilic a t position 1, and are oxidizablea t position 4 to the corresponding sulphone. X-Ray crystallographic studies of bis- [ct-(2,6-dibrorno-phenylhydrazono) benzyl] sulphide confirm the symmetrical structure of hydrazonoyl sulphides.of Chemistry, Brock University, St.Catharines, Ontario LS2 3A1, CanadaWE have developed two methods for the synthesis ofsimple IH-4,1,2-benzothiadiazines (Scheme 1). Thefirst involves the reaction of suitably substitutedhydrazonoyl halides with thioacetate ion, normally inrefluxing a~etonitrile.l-~ The second involves basictreatment of suitably substituted N-acetyl-N-ary1-N'-thioaroylhydrazines, normally with triethylamine inrefluxing a~etonitrile.~ Other reactions leading toI. T. Barnish and M. S. Gibson, J .Chem. SOC. ( C ) , 1970, 854.P. D. Callaghan and M. S. Gibson, J . Chem. SOC. ( C ) , 1970,I. T. Barnish, P. D. Callaghan, and M. S. Gibson, J.C.S.P. D. Callaghan, M. S. Gibson, and A. J. Elliott, J.C.S.2106.Perkin I , 1974, 215.Perkin I, 1975, 1386.benzothiadiazines include the preparation of 3-phenylazo-1H-4,1 ,Zbenzothiadiazine by refluxing dithizone inacetic acid and of l-methyl-3-phenyl-4,1,2-benzo-thiadiazine by treatment of N'-methyl-N'-phenyl-benzothiohydrazide with iodine in benzene,6 but it is notknown how general these reactions are. The firstmethod suffers from the drawback that frequently mat-erial is diverted to the production of the correspondingW. S. McDonald, H. M. N. H. Trving, G. Raper, and D. C.Rupainwar, Chem.Comm., 1969, 392; C. H. Carlin and A. H.Convin, Abstracts, 157th National Meeting of the AmericanChemical Society, Minneapolis, April 1969.D. H. R. Barton, J. W. Ducker, W. A. Lord, and P. D.Magnus, J.C.S. Perkin I , 1976, 381977 193hydrazonoyl sulphide, S(CPh:N*NH*C,H,YZ),. In thisrespect the second method is more attractive and we havedirected our attention to extending its scope.In our earlier experiments,ld4 ring closure had onlybeen effected in cases where the substituent 2 was elec-tron-attracting, and then not in all cases. With Y =Br and 2 = H or Me, cyclization was not observed. Wefirst considered the question of whether the 2,4-position-ing of the substituents Y and 2 relative to nitrogen wasmandatory, and have studied the behaviour of 2,5- and2,6-dibromo- and 2,4,6-tribromo-phenylhydrazine deriv-atives in these reactions. The arylhydrazine wasAcPhCX=N*NH 0 \ Z - Ph(S ‘“DZY tSCHEME 1benzoylated and the resulting benzohydrazide con-veniently converted into the hydrazonoyl chloride byreaction with phosphoroyl chloride.Treatment of thehydrazonoyl chloride with sodium thioacetate in ace-tonitrile at room temperature (at reflux for the tribromo-compound) gave the anticipated N’-acetyl-N’-aryl-benzothiohydrazide together with the hydrazonoyl sul-phide. Each of these benzothiohydrazides was convertedinto the corresponding 1 -acety1-4,1,2-benzothiadiazinewhen refluxed with triethylamine in acetonitrile, thoughthe reaction was sluggish with the 2,5-dibromo-compound.The 1H n.m.r. spectra of the derived thiadiazines areconsistent with their structural assignments. Forexample, relative to 6-bromo-3-phenyl-1 H-4,1,2-benzo-thiadiazine, the signal due to the 8-proton appears a tconsiderably lower field in the spectrum of the 7-bromo-isomer, and in that of the 8-bromo-isomer the signal dueto the 1-proton (N-H) is considerably further downfield,consistent with the position of the bromine atom adjacentto nitrogen.It is thus clear that these cyclization re-actions are not limited to cases in which 2 is orientedpara to nitrogen, but some general electron withdrawalassociated with the substituent(s) seems necessary.In our earlier work, difficulties had been encounteredwith reactions of thioacetate ion with hydrazonoylhalides in which Y or 2 was a nitro-gr~up.~ Thisproblem has been further examined in the context ofalternative syntheses of 1 -ace t yl-6-ni t ro-3-phenyl-4,1,2-benzothiadiazine. We first prepared N’-acetyl-N’- (2-bromo-4-nitropheny1)benzothiohydrazide in the normalway, though it was not obtained pure.Refluxing withacetonitrile-triethylamine gave a mixture from which thethiadiazine was isolated in 26% yield. The same com-pound was produced by acetylating the product obtainedby the reaction of benzothiohydrazide with 1-fluoro-2,4-dinitrobenzene in acetonitrile-triethylamine (Scheme2). These experiments established both the compati-Aci, PhCS. NH.NH2- NEt 3i i . A c Z OSCHEME 2bility of the nitro-group with the reaction conditions andits displaceability in ring closure.However the processesare complicated by side reactions and are not syntheti-cally at tractive.We also considered the possibility of avoiding stepsinvolving the hydrazonoyl halide. This approach seemedmost feasible with the more stable sulphur nucleophiles.Thus N’-(2,6dibromophenyl) benzohydrazide and 4-nitrobenzenethiol react slowly in boiling acetonitrile-triethylamine to give the benzothiadiazine in a processthat may have more generality (Scheme 3).With a number of benzothiadiazines available, wehave undertaken a brief study of their reactions. Acidichydrolysis of l-acetyl-4,1,2-benzothiadiazines to lH-4,1,-2-benzothiadiazines and their regeneration by acetyl-ation had been noted previous1y.l We have foundthese reactions, not surprisingly, to be sluggish with the8-substituted compounds.The 1H-compounds are sus-ceptible to electrophilic substitution at positions 6 and 8.C H N 0 2 - 4i 6SCHEME 3Thus pyridinium perbromide converts both 6- and 8-brom0-3-phenyl-lH-4,1,2-benzothiadiazines into the 63-dibromo-compound.The lH-4,1,2-benzothiadiazines are feebly nucleo-philic at the 1-position (cf. acetylation). This positionmay also be methylated with methyl toluene-4-sulphon-ate, providing an alternative source of 1-methyl deriv-atives.6 Aryl halides such as l-fluoro-2,4-dinitrobenzenewill similarly arylate the 1-position. A 1-nitroso-derivative was also prepared by using pentyl nitrite, butwas unstable and not completely characterized.Lastly,one of the 1H-benzothiadiazines was oxidized to thesulphone with hydrogen peroxide in acetic acid.One problem which had been incompletely resolved inprevious work was the structure of the hydrazonoylsulphides which accompany thiohydrazide derivativesand benzothiadiazines in many of these reactions. Thesehave been formulated throughout as hydrazonoyl sul-phides (I), consistent with methods of formation andwith spectral data, but the unsymmetrical structure (11),formally derivable by rearrangement of (I), has not beencompletely dismissed. The question of the correctformulation of these compounds has been resolved byX-ray studies on bis- [ a- (2,6-dibromophenylhydrazono) -benzyl] sulphide. The molecules of this material ar194 J.C.S.Perkin Irequired crystallographically to have either C, symmetryin space group Aba2 or C2h symmetry in space groupCmca. That is, the four molecules in the unit cell mustoccupy the four-fold (4a) positions in Aba2, or the 4a or4b positions in Cmca.' The crystallographic require-ment for symmetry rules out structure(II), but is consis-tent with structure(1).PhC=N.NHArIISPhCZN-NHArArN=NH*CSPhP hC=N*NHArIEXPERIMENTALlH N.m.r. spectra were recorded with a Varian A60instrument (tetramethylsilane as internal reference). Massspectra were obtained with an A.E.I. MS30 double-beaminstrument (heated probe) operating a t 70 eV; data arerecorded for the lowest mass isotopic species, bromineexcepted.2,5-Dibromo~henylhydrazine.-This compound (17.1 g,goyo), prepared from 2,5-dibromoaniline by diazotizationand reduction with tin(1r) chloride in the normal.way,, hadm.p. 87-89".N'-( 2,5-Dibromophenyl) benzohydrazide.-This hydrazide(4.9 g, 71y0), from treatment of the hydrazine with benzoylchloride-triethylamine, crystallized from ethanol as needles,m.p. 169-170" (Found: C, 41.95; H, 2.8; Br, 43.45.C,,HloBr,N,O requires C , 42.1; H, 2.95; Br, 43.25%).N'-(2,5-DibromophenyZ)benzothiohydrazide (1.95 g, 40%),from the hydrazine and carboxymethyl dithiobenzoate-M-sodium hydroxide 4 9 8 a t 40-50 "C, crystallized from lightpetroleum (b.p. 60-90 "C) as yellow prisms, m.p. 149"(Found: C, 40.05; H, 2.55; S, 8.25. C,,HloBr2N2S requiresC, 40.45; H, 2.6; S, 8.3%).Similarly prepared were N'-( 2,6-dibromophenyl) benzo-hydrazide (7.9 g, 66y0), m.p.150-152" (lit.,3 150-151") ;N'-(2,6-dibromophenyZ)benzothiohydrazide (2.4 g, 82% crude,containing persistent orange by-product), m.p. 156-158" ;N'-(2,4,6-tribromophenyl)benzohydrazide (13.4 g , 70y0),from ethanol as rods, m.p. 172-173" (lit.,Q 172") ; N'-(2,4,6-tribromopheny1)benzothiohydrazide (7.17 g, 78%) [frombenzene-light petroleum (b.p. 30-60 "C)] as pale yellowprisms, m.p. 135" (Found: C, 33.85; H, 1.95; N, 6.0.C13H,Br3N,S requires C, 33.55; H, 1.95; N, 6.0%).Hydrazonoyl Chlorides.-These were prepared from thehydrazides by treating with pbsphoroyl chloride for (a)12 h a t 60 OC, or (b) 6 h a t reflux. When cool, the mixturefrom (a) was added dropwise to ice-cold sodium hydrogencarbonate solution with stirring, and the product was col-lected, washed, dried , and crystallized.Alternatively, (b)the mixture was evaporated in vacuo and the resulting gumwas triturated with ethanol to give a solid product whichwas crystallized.(a) N'-(2,5-Dibromophenyl)benzohydrazide ( 10.7 g) andphosphoryl chloride (50 ml) gave N-a-ch1orobenzyZidene-N'-(2,5-dibromophenyZ)hydrazine ( 10.5 g, 89%), which crystal-lized from acetonitrile as needles, m .p. 98-99" (Found :C, 40.1; H, 2.5; N, 7.35. C13HQBr,C1N, requires C , 40.15;7 ' International Tables for X-ray Crystallography,' vol. I,Kynoch Press, Birmingham, 1965, pp. 127, 153.8 K. A. Jensen, H. R. Baccaro, 0. Buchardt, G. E. Olsen,C.Pedersen, and J . Toft, Acta Chem. Scand., 1961, 15, 1109.H, 2.3; H, 7.2%). N'-(2,6-libromophenyl)benzohydrazide(5.40 g) gave N-a-c/zZorobenzyZidene-N'-( 2,6-dibromophenyZ)-hydrazine (5.22 g, 91%) as cream needles, m.p. 65" (fromacetonitrile) (Found: C, 40.25; H, 2.45; N, 7.25%).Similarly prepared were N-a-chlorobenzy1idene-N'- (4-bromopheny1)hydrazine (65y0), m .p, 123", and N-a-chloro-benzylidene-N'-(4-~hlorophenyl) hydrazine ( 74y0), m.p. 106"(1it.,lo 138-139, 108-110").(b) N'-(2,4,6-Tribromophenyl)benzohydrazide (8.2 g)gave N-a-chZorobenzyZidene-N'-( 2,4,6-tribromophenyl) hydra-zine (7.5 g, 88y0), m.p. 108-109°, as rods (from acetonitrile)(Found: C. 33.3; H, 1.65; N, 6.15. C13H8Br,C1N, requiresC, 33.4; H, 1.7; N, 6.0%).N'-A cetyl-N '-arylbenzothiohydrazides and Hydrazonoyl Sul-phides.-General conditions for reaction of hydrazonoylhalides with sodium thioacetate in acetonitrile a t roomtemperature correspond with those previously reported.2Hydrazonyl sulphides were recovered by virtue of theirsparing solubility in hot ethanol ; acetyl-thiohydrazideswere isolated from the ethanolic extracts by dilution withwater, with addition of acetic acid if necessary to inducecoagulation.For reference purposes, N-a-bromobenzyl-idene- N'- (2,4-dibromophenyl) hydrazine was also treatedwith sodium thioacetate in acetonitrile-water mixtures ofcomposition 19 : 1 and 9 : 1. Yields of the correspondingacetyl-thiohydrazide and hydrazonoyl sulphide were (a)83-88 and lO-ll%, and (b) 91-95 and 8% respectively.N-a-Bromobenzy1idene-N'- ( 2 4-dibromophenyl) hydrazine(4.33 g) gave the hydrazonoyl sulphide (0.62 g 9%), m.p.201-202" (decomp.), as rods (from benzene) [lit.,l 200-202" (decomp.) J , and N'-acetyl-N'-( 2,4-dibromophenyl)benzothiohydrazide (4.07 g, go%), m.p.177-178" (decomp.)as yellow prisms (from ethanol) (Found: C, 42.2; H, 2.75;N, 6.6. Calc. for Cl,Hl,Br2N,0S: C, 42.05; H, 2.8; N,6.55%).N-a-Chlorobenzy1idene-N'- (2,5-dibromophenyl) hydrazine(1.3 g) gave bis-[a-(2,5-dibromophenylhydrazono)benzy~ sul-$hide (0.12 g, 5.5%), m.p. 210" (decomp.), as rods (frombenzene) (Found: C, 42.1; H, 2.5; N, 7.6. C2,H18Br4N4Srequires C, 42.3; H, 2.45; N, 7.6%), and N'-acetyl-N'-(2,5-dibromopheny1)benzothiohydrazide (0.85 g, 60%) , m.p.146-147", as yellow needles (from ethanol) (Found: C, 42.2;H, 2.85; N, 6.7%).N-a-Chlorobenzy1idene-N'- ( 2,6-dibromophenyl) hydrazine(8.0 g) gave bis-[a-(2,6-dibrornophenyZhydrazono)benzy~ sul-$hide (1.8 g, 12%), m.p. 200-201" (decomp.), as creamneedles (from toluene) (Found: C, 42.6; H, 2.5; N, 7.45%),and N'-acetyl-N'-(2,6-dibromo~henyl)henzothiohydrazide (5.5g, 62y0), m.p. 150-151" (decomp.), as yellow prisms (fromaqueous ethanol) (Found: C, 42.3; H, 2.85; N, 6.5%).The latter compound. was identical (m.p., t.l.c., and i.r.spectrum) with that produced by refluxing N'-( 2,6-dibromo-pheny1)benzothiohydrazide with acetic anhydride-aceticacid for 20 min.N-a-Bromobenzy1idene-N'- ( 2-bromo-4-fluorophenyl) hy-drazine (5.0 g) gave the hydrazonoyl sulphide (0.82 g, lo%),m.p.184-186' (decomp.), as blades (from benzene) [lit.,l184-1 85" (decomp.)], and N'-acetyZ-N'-(2-bromo-4-fluoro-$henyl)benzothiohydrazide (3.6 g, 72%), m.p. 156-157"(decomp.), as yellow prisms (from ethanol) ; the latter com-pound was essentially pure (t.1.c.) and was used directly forconversion into the thiadiazine.@ G. Ponzio and C. Macciotta, Guzzetta, 1914, 44(1), 269.10 Cf. A. F. Hegarty, J. A. Kearney, and F. L. Scott, J.C.S.Perkin 11, 1973, 1422; A. F. Hegarty, personal communication1977In the case of N-a-chlorobenzylidene-N'-( 2,4,6-tribromo-phenyl) hydrazine (6.0 g), the reaction was conducted a treflux for 1 h. The mixture apparently contained no thio-diazine. The normal work-up gave the hydrazonoyl sul-phide (1.18 g, l l x ) , m.p.198-200" (decomp.), as rods(from benzene) [lit. 196-198" (decomp.)], and N'-acetyl-N'-( 2,4,6-tribromophenyl)benzothiohydrazide (4.12 g, 65%)m.p. 123-125" (decomp.), as yellow prisms (from benzene) ;essentially pure (t.1.c.) ; the latter compound was converteddirectly into the thiadiazine.Two hydrazonoyl sulphides were prepared from the hydra-zonoyl chloride and sodium sulphide nonahydrate in thenormal way : bis-[a-( 4-bromo~henylhydrazono) benzyq sul-Phide (50%), m.p. 202" (decomp.), as cream leaves (frombenzene) (Found: C, 54.0; H, 3.65; N, 9.4; S, 5.6.C,,H,,BrClN,S requires C, 53.8; H, 3.45; N, 9.65; S, 5.5%) ;and bis-[a-(4-chlorophenyZhydrazono)benzyZl sulphide (40y0),m.p.199" (decomp.), as cream needles (from benzene)(Found: C, 64.15; H, 4.05; C1, 14.45; S, 6.2. CzsHzoC1,-N,S requires C, 63.55; H 4.1; C1 14.45; S 6.5%).Cyclization of N'-A cetyl-N'-ary1benzothiohydrazides.-Thegeneral method was that described previously except wherenoted othe~wise.~N'- Acetyl-N'- ( 2,5-dibromophenyl) benzothiohydrazide(1.0 g) gave, after 20 h under reflus, l-acetyZ-7-bromo-3-phenyZ-4,1,2-benzothiadiazine (0.38 g 44%) as cream needles,m.p. 123-125" (from benzene). The compound retainedimpurities and so a sample (0.6 g) was deacetylated (3 hreflux with ethanol-conc. hydrochloric acid) to give 7-bromo-3-phenyl- lH-4,1,2-benzothiadiazine (0.37 g, 70%),which crystallized from ethanol as long yellow needles, m.p.149-150" (Found: C, 51.15; H, 2.95; N, 9.05.C13H9-BrN,S requires C, 51.15; H, 2.95; N, 9.2%) ; 6(CS,) 7.82-7.62 (2 H, m), 7.45-7.15 (4 H, m), 7.10-6.76 (2 H, m), and6.75-6.62 (1 H, distorted d). Acetylation (1 h reflux withacetic anhydride-acetic acid) gave the acetyl derivative,which crystallized from ethanol (charcoal) as needles, m.p.124-125' (Found: C, 51.85; H, 3.4; N, 7.9. C,,H,,-BrN,OS requires C, 51.9; H, 3.2; N, 7.9y0), identical withthe foregoing sample.N'-Acetyl-N'- (2,6-dibromophenyl) benzothiohydrazide(5.1 g) gave, after 8 h under reflux, l-acetyE-8-bromo-3-phenyl-4,1,2-benzothiadiazine (3.5 g, 85%) as cream prisms, m.p.127-128' (from benzene) (Found: C, 51.65; H, 3.2;S, 9.2. C1,HllBrN,OS requires C, 51.9; H, 3.2; S, 9.25%).Refluxing this compound (3.4 g) with ethanol-conc.hydro-chloric acid for 36 h gave a crude product which was chro-matographed (Florisil ; benzene-chloroform) to give startingmaterial (1.2 g), an unidentified red product, and 8-bromo-3-Phenyl-lH-4,1,2-benzothiadiazine (0.4 g, 13%) as yellowneedles, m.p. 75" (from ethanol) (Found: C, 51.15; H, 3.1;N, 9.05%) ; 6(CS,) 8.20-7.95br (1 H, s), 7.90-7.67 (2 H, m),7.45-7.15 (4 H, m), and 7.00-6.60 (2 H, m).N'- Acetyl- N'- (2-bromo-4-fluorophenyl) benzothiohydra-zide (3.0 g) gave l-acetyl-6-fluoro-3-phenyl-4,l , 2-benzothiadi-zine (1.1 g, 48y0), m.p. 173-174" (lit. 1 183"). Deacetyl-ation of a sample (1.0 g) gave 6-fluor0-3-phenyZ-lH-4,1,2-benzothiadiazine (0.72 g, 81%) as long yellow needles, m.p.106-107" (from ethanol); an analysed sample had m.p.107--108"(Found: C, 64.0; H, 3.8; F, 7.9; N, 11.3; S, 13.3.Cl,H,FN,S requires C, 63.9; H, 3.7; F, 7.8; N, 11.5; S,13.1 %).N'-Acetyl-N'-( 8,4,6-tribromophenyl) benzothiohydrazide(1.0 g) gave after 6 h under reflux, l-acetyl-6,8-dibromo-3-phenyl-4,1,2-benzothiadiazine (0.45 g, 55%) as needles, m.p.129-130" [from benzene (charcoal)], identical with thesample described below.l-Acetyl-6-nitr0-3-phenyl-4,1,2-benzothiadiazine .--Previousattempts to prepare this compound were unsuccessful. Thepresent experiments have been successful, but persistentcontaminants have prevented the preparation of samplesgiving satisfactory analytical figures.(a) N-a-Bromobenzylidene-N'-(2-bromo-4-nitropheny1)-hydrazine 11 (5.0 g) and sodium thioacetate (2.5 g) gave, inthe normal way, the hydrazonoyl sulphide (0.75 g 10%) asyellow prisms, m.p.227-228' (decomp.) (from toluene) ;v,,,. (KBr) 3 260 cm-1 (N-H). The reaction liquor yieldeda rusty red solid (3.85 g), m.p. 62-66", containing threecomponents (t.1.c.) of which one appeared t o be the desiredacetyl-thiohydrazide. The crude product (3.0 g) was boiledunder reflux for 4 h in acetonitrile-triethylamine and theproduct isolated by dilution with water. Chromatographyon Florisil gave l-acetyl-6-nitro-3-phenyl-4,1,2-benzothiadi-zine (0.58 g, 24%) as fluorescent golden needles, m.p. 182-183" (from ethanol); vmx. 1690 cm-l (GO); G(CDC1,)8.20-7.85 (5 H, m), 7.65-7.20 (3 H, m), and 2.55 (3 H, s);mle 313 (M+), 292, 290, 284, 283, 277, 273, 271, 241, 238, 225,185, 163, 149, 135, 121, 105, 103, 83, 81, 78, and 77.De-acetylation gave a red solid, m.p. 147-155' which contained6-nitro-3-phenyl- lH-4,1,2-benzothiadiazine. This was es-tablished by correlation of i.r. and mass spectra (see below) ;the mass spectrum showed additional peaks at mle 386, 358,351, 322, 299, and 284 due to other material.(b) Benzothiohydrazide 8 (1.52 g), l-fluoro-2,4-dinitro-benzene ( 1.86 g) , acetonitrile (20 ml) , and triethylamine(5 ml) were boiled under reflux for 1 h, the solution turningdeep red. Chromatography on Florisil gave 6-nitro-3-phenyl-lH-4,1,2-benzothiadiazine (0.49 g, 18%) as fluores-cent red needles, m.p. 159-160"; vmax. 3 295 cm-l (N-H) ;G(Me,SO) 8.33-8.25 (1 H, m), 7.78-7.20 (5 H, m), and6.71-6.48 (3 H, m); mle 271 (M+), 255, 241, 237, 225, 195,187, 177, 165, 149, 138, 135, 123, 122, 121, 105, 103, 78, and77.Treatment with acetic anhydride (1 11 reflux) gave the1-acetyl derivative, identical (mixed m.p.and i.r. and lHn.m.r. spectra) with the foregoing sample.7-Bromo- 1 - (4-nitrophenyl) -3-phenyl- lH-4,1,2-benzothiadia-zine.-A mixture of 4-nitrobenzenethiol (0.42 g) , N'- (2,5-dibromophenyl) benzohydrazide (1 .O g), ethanol ( 15 nil),and triethylamine (5 ml) was boiled under reflux for 72 h.Solvents were removed in vacuo. 7-Bromo- l-(Cnitrophenyl)3-PhenyZ-lH-4,1,2-benzothiadiazine (0.46 g, 40%) crystal-lized from ethanol as orange prisms, m.p. 207-208" (Found :C, 53.55; H, 3.05; N, 9.6.C,,H,,BrN,O,S requires C,53.5; H, 2.85; N, 9.35%); m/e 4271425 (M+), 4111409,3951393, 3811379, 346, 3241322, 307, 305, 303, 278/276, 197,196, 153, 121, 103, 95, and 77.Reactions of lH-4,1,2-Benzothiadiazines.-(a) 6- and 8-Substitution. (i) Freshly prepared pyridinium perbromide( 1.6 g) and 6-bromo-3-phenyl- lH-4,1,2-benzothiadiazine(1.52 g) were stirred together in glacial acetic acid (50 ml) a troom temperature for 2 h. The colour of the mixturechanged from dark brown to yellow. The solid was filteredoff, washed, and crystallized from ethanol to give 6,S-di-brom0-3-~henyl-lH-4,1,2-benzothiadiazine (1.82 g, 95%) asyellow needles, m.p. 108-109" (Found: C, 40.95; H, 2.3;Br, 41.4. C,,H,Br,N,SrequiresC, 40.6; H, 2.1; Br, 41.6%):6(CC14) 7.90 (1 H, s), 7.71-7.59 (2 H, m), 7.29-7.19 (4 H,m), and 7.05-6.98 (1 H, distorted d).The same compoundl1 J. M. Burgess and M. S . Gibson, Tetrahedron, 1962, 18, 1001196 J.C.S. Perkin Iwas produced under similar conditions from 8-bromo-3-phenyl- lH-4,1,2-benzothiadiazine.The dibromo-compound (0.5 g) was boiled with aceticanhydride (5 ml) for 36 h to give the 1-acetyl derivative(0.52 g, 94%), which crystallized from ethyl acetate asneedles, m.p. 129-130", identical with the foregoing sample(Found: C, 42.4; H, 2.5; N, 6.55. C,,H,,Br,N,OS requiresC, 42.25; H, 2.35; N, 6.55%); G(CS,) 8.00-7.79 (2 H, m),7.71-7.65 (1 H, distorted d), 7.50-7.25 (4 H, m), and 2.33(ii) 6-Fluoro-3-phenyl- lH-4,1,2-benzothiadiazine (1 .O g)similarly gave 8-brouno-6-$uoro-3-pIzenyl- lH-4,1,2-benzo-thiadiazine (0.85 g, 64%) as pale yellow needles, m.p.99-100' (from methanol) (Found: C, 48.4; H, 2.45; N, 8.5.C,,H,BrFN,S requires C, 48.3; H, 2.5; N, 8.65%).(i) A mixture of 6-bromo-3-phenyl- 1H-4, l12-benzothiadiazine ( 1.52 g), methyl toluene-4-sulphonate(0.95 g), and acetonitrile (30 ml) was boiled under reflux for144 h. Chromatography (Florisil ; pentane-chloroform)gave the starting thiadiazine (0.62 g) and 6-bromo- 1-methyl-3-phenyl-4,lI2-benzothiadiazine (0.72 g, 45%) as yellow rods,m.p. 63-64' (Found: C , 52.5; H, 3.45; S, 10.0. C14H1,-BrN,S requires C, 52.7; H, 3.45; S, 10.05%); 6(CC1,)7.90-7.71 (2 H, m), 7.38-7.12 (5 H, m), 6.61-6.50 (1 H,distorted d), and 3.37 (3 HI s).(ii) A mixture of 6-bromo-3-phenyl- 1 H-4,1,2-benzothia-diazine (0.72 g), l-fluoro-2,4-dinitrobenzene (0.43 g),acetonitrile (15 ml), and triethylamine (5 ml) was boiledunder reflux for 6 h ; solvents were removed in uacuo.Crystallization from ethyl acetate gave 6-brouno- 1-( 2,4-di-nitrophenyl) -3-pheny1-4,1,2-benzothiadiazine as red needles,m.p.213-214" (Found: C, 48.2; H, 2.35; N, 11.55.C,,H,,BrN,O,S requires C, 48.4; H, 2.35; N, 11.9%);G(Me,SO) 8.17-7.40 (4 H, m), 7.25-6.61 (6 H, m), and6.21-6.05 (1 H, distorted d).(iii) Isopentyl nitrite (0.29 g, 1 equiv.) was added during(3 HI s ) .(b) 1-Substitution.10 min to a stirred solution of 6-bromo-3-phenyl-lH-4,1,2benzothiadiazine (0.76 g) in ethanol (30 ml) and hydrochloricacid (1 ml) a t room temperature.After 2 h, the yellowsolid was filtered off, washed, and dried. Crystallizationfrom acetone (at - 78 "C) gave the 1-nitroso-derivative(0.45 g , 54%) as yellow needles, m.p. 92-94", which slowlydecomposed at room temperature ; G(CDC1,) 8.08-7.81(2 H, m), 7.72-7.63 (1 H, d), and 7.60-7.20 ( 5 H, m).Microanalytical figures were discrepant.A solution of 6-brom0-3-phenyl-lH-4,1,2-benzothiadiazine (0.76 g) in acetic acid (30 ml) and 6% hy-drogen peroxide (10 ml) was boiled under reflux for 15 minand then cooled. Water (30 ml) was added and the solidwas filtered off, and dried. Crystallization from ethanol-ethyl acetate gave 6-bromo-3-phenyl-lH-4,1,2-benzothiadi-aziize 4,4-dioxide (0.55 g , 6604,) as pale pink prisms, m.p.249-250" (Found: C, 46.0; H, 2.85; N, 8.2. C1,H,-BrN,O,S requires C , 46.3; H, 2.7; N, 8.3%); mle 338/336(Mf), 2931291, 274/272, 2471245, 243, 2351233, 231, 219, 216,207, 205, 199, 198, 197, 171, 169, 166, 165, 162, 143, 135, 123,118, 105, 104, 103, 78, and 77.X-Ray Crystallographic Studies of Bis-[cr-(2,6-dibromo-phenylhydrazono) benzyq Sulphide.-Crystals of the hydra-zonoyl sulphide were examined under a polarizing micro-scope. A small single crystal was chosen and sealed in aLindemann capillary tube. Oscillation and Weissenbergphotographs were taken with nickel-filtered Cu-K, radiation.The following orthorhombic unit cell parameters wereobtained from these photographs: a = 6.86, b = 15.85,c = 24.49 A, D, = 1.84, D,(flotation) = 1.88 g ~ m - ~ , 2 = 4,space group Cmca or Aba2.We thank Mr. N. Hughes for initial study of the phos-phoryl chloride reaction, and the National Research Councilof Canada for financial support.[6/1438 Received, 22nd July, 19761(c) Oxidation
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