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The 1-(2,2-disubstituted alk-1-enyl)-5-phenyltetrazoles 2 and 4 are prepared from 1-methyl-5-phenyltetrazole and 5-phenyl-1-trimethylsilylmethyltetrazole by formation and appropriate interception of the α-lithioalkyl derivatives. Photolysis of the tetrazoles 2a and 4 gives the stable 4H-imidazoles 9 and 5, respectively. Similar photolysis of the tetrazole 2b gives the tetrazolophenanthrene 12 by an oxidative photocyclisation which is faster than nitrogen extrusion from the tetrazole ring. However, on further irradiation the tetrazolophenanthrene 12 can be transformed into the polycyclic 4H-imidazole 13. The 4H-imidazoles all undergo [1,5] alkyl or aryl shifts to carbon when heated, 5, 7, 9 and 13 giving 6, 8, 10 and 14 respectively.

The addition of trimethylsilyloxy phosphorus (III)derivatives generated in situ to imines at room temperature provides a mild selective and high yielding route to α-aminoalkylphosphorate and α-aminoalkylphenylphosphinate esters. Isocyanates and carbodiimides react similarly to give phosphonoureas and phosphonoguarnidines respectively aldehydes and ketones are much less reactive and cyanides are inert.

Photolytic or rhodium catalysed decomposition of α-diazo-β-ketophosphonamidates and intramolecular C–H insertion of the resulting carbene intermediates is the key step in the synthesis of mono and bicyclic 1,2-azaphosphetidines.

A short synthsis of the pentacyclic marine alkaloid ascididemin 1 (four steps, 21% yield) from 1,10-phenanthroline 16 is described. The key step, photocyclisation of the quinoneimine 14 in sulphuric acid, is the first such aza stilbene photocyclisation of a quinoneimine. Intermediate 14 is prepared in a single, but low yielding, step from the quinone 4 in an aza Wadsworth-Emmons reaction, or in much better yield from the epoxide 17 by treatment with 2- iodoaniline and triethylaluminium, followed by oxidation with barium manganate.

1,3,2-Dithiazol-1-ium chloride 6 and 5-chloro-1,3,2-dithiazol-1-ium chloride 7 have been prepared by the reaction of trimethylsilyl azide with 1-chloroethane-1,2-bis(sulfenyl chloride) and 1,2-dichloroethane-1,2-bis(sulfenyl chloride) respectively. The corresponding neutral 1-λ4δ2, 3,2-dithiazole-4-thione 8 and 5-chloro-1-λ4δ2,3,2-dithiazole-4-thione 18 were unexpectedly obtained by treatment of these salts with base. Methylation and benzylation of the thione 8 provided the 5-methylthio-1,3,2-dithiazol-1-ium 9 and 4-benzylthio-1,3,2-dithiazol-1-ium 12 salts, which on treatment with base afforded 5-methylthio-10 and 5-benzylthio-1-λ4δ2,3,2-dithiazole-4-thione 13 respectively; further alkylation provided a route to symmetrical difunctionalised cations such as 4,5-dimethylthio-1,3,2-dithiazol-1-ium iodide 11. Treatment of the dithiazolium chloride 7 with ammonia or aniline leads to 5-amino-19 and 5-anilino-1-λ4δ2,3,2-dithiazole-4-thione 20 respectively.

Anthranilic acid and 4,5-dichloro-1,2,3-dithiazolium chloride 1 give the delicate dithiazoloimino carboxylic acid 8 which on mild thermolysis gives 2-cyano-3,1-benzoxazin-4-one 6 and with triphenylphosphine gives 2-cyano-3,1-benzothiazin-4-one 7, both quantitatively; in general N-aryliminodithiazoles 2 with triphenylphosphine give the corresponding cyanothioformanilides 3, providing a route to these compounds from anilines in two mild steps.

4,5-Dichloro-1,2,3-dithiazolium chloride 1 reacts with fluoroanilines (see Table 1) to give the iminodithiazoles 5 in very high yield. Thermolysis of the latter gave the corresponding 2-cyanobenzothiazoles 6 together, in some cases, with the cyanoimidoyl chlorides 7. This reaction sequence provides modest yields of 2-cyanobenzothiazoles from the corresponding aniline, in two steps. Treatment of the iminodithiazoles with m-chloroperbenzoic acid in dichloromethane at or below room temperature opened the heterocyclic ring to give the N-arylcyanothioformamides (e.g.8→10), except for the p-nitrophenyl compound which gave p-nitrophenyl isothiocyanate 14 in high yield.

The cyclobutanone oxime 6 reacts with disulfur dichloride to give two unexpected 10π pseudoazulenes in low yield: the dark blue cyclopenta-1,2-dithiole 7 and the orange cyclopenta-1,2-thiazine 8; the benzo derivative 14 of this oxime gives the analogous benzo product 15 together with the methylene indene 16 in high yield; mechanisms based on abnormal Beckman rearrangements are proposed for the formation of all of these products.

The first N-oxides of the 1,2,4-thiadiazole ring system are prepared by condensation of benzamidoximes with 4,5-dichloro-1,2,3-dithiazolium chloride 1; they are shown by 15N-labelling to be 4-oxides and a mechanism is proposed for their formation.

2-Cyanobenzimidazoles 6 are readily prepared from 1,2-diaminobenzenes 4 and 4,5-dichloro-1,2,3-dithiazolium chloride 1, either directly or through thermal or acid-catalysed rearrangement of the isolated imine intermediates 5; thermolysis of the imine 5b at 140–150°C simultaneously generates diatomic sulfur, S2, as shown by its interception.

Nucleophilic displacement of halide by alkoxide in pyridazines, phthalazines, a thiazole and a thiadiazole is unexpectedly activated by acetamido anion substituents compared to neutral amido and amino substituents.

Novel 3,1-benzoxazinones, 3,1-benzothiazinones and 4-alkoxyquinazolines have been synthesized via N -aryl-1,2,3-dithiazoles derivatives. The antibacterial and antifungal activity of these compounds were measured; the dithiazoles are significantly active against fungi.

8-Aminoquinolines and the dithiazolium salt 1 give N-(8-quinolinyl)iminodithiazoles 4 which undergo an unusual type of thermal rearrangement to give the new imidazo[5,4,1-ij]quinoline-4-thiones 6; it appears that the thione sulfur is delivered intramolecularly (9 → 10).

The cyclobutanone oxime 6 reacts with disulfur dichloride, N-chlorosuccinimide, and Hunig's base to give three unexpected 10 π pseudoazulenes in low yield: the dark blue cyclopenta-1,2-dithiole 7, its red isomer 10, and the orange cyclopenta-1,2-thiazine 8. The benzo derivative 14 of oxime 6 gives an analogous benzo product 15 together with the methylenoindene 16 in high yield. The formation of all of these products can be explained by a unified mechanism based on initial abnormal Beckmann rearrangement of the oximes to cyanides followed by cyclization and/or exhaustive chlorination and dehydrochlorination. The 1,2-dithiole 7 is synthesized independently from 1-(cyanomethyl)cyclopentene 11 and the above reagents, and 1-cyanomethylindene 17 is similarly converted into methylenoindenes 18 and 19, which are isomers of product 16. Structures 7 and 15 are confirmed by X-ray crystallography, and compounds 7, 8, 15, 16, 18, and 19 show birefringence on heating in a hot stage polarizing microscope indicating, mo...

1-Alkyl-5-amino-3-aryl-4-cyanopyrazoles, useful intermediates for fused heterocyclic systems, are synthesised by a one-pot three-step procedure from acid chlorides, malononitrile and alkylhydrazines. The regiochemistry of the hydrazine incorporation was proved in each case by X-ray crystallography and NMR spectroscopy.

A new, direct synthesis is described for the relatively rare but synthetically very versatile quinazoline-2-carbonitriles from antranilonitriles and 4,5-dichloro-1,2,3-dithiazolium chloride 1. Treatment of iminodithiazole 6, from 4,5-dimethoxyanthranilonitrile and the salt 1, with alcohols and a base gives 4-alkoxyquinazoline-2-carbonitriles 8 in good yield. Treatment of the parent iminodithiazole 2 (R = H; X = CN) with alcohols and sodium hydride gives the analogous quinazolines 12 in lower yield, though these yields are much improved and the reaction times reduced under microwave irradiation. Alternatively the imine 6 can be converted into the more reactive cyanothioformamide 7 which on brief heating in alcohols gives the same quinazolines 8 in high yield.

Microwave irradiation of neat N-arylimino-1,2,3-dithiazoles 2 in screw-capped glass vials gives 2-cyanobenzothiazoles 3. rapidly and cleanly in good yield.

Primary aromatic amines condense with 4,5-dichloro-1,2,3-dithiazolium chloride 1 to give high yields of the N-aryl imines 2 which on heating give 2-cyanobenzothiazoles 3, thus providing a simple two-step route to these heterocycles from the appropriate aniline. This thermolysis is favoured by electron donating substituents in the aniline ring, and retarded by electron withdrawing groups in favour of a second pathway in which both dithiazole sulfur atoms are lost to form cyanoimidoyl chlorides 4. This is the sole pathway when both aniline ortho positions are substituted. Analogous N-alkyl imines 5, prepared from the salt 1 and the bis(trimethylsilyl) derivatives of the amine, also decompose with loss of both sulfur atoms as singlet diatomic sulfur, S2. 4-Chloro-5-methylimino-5H-1,2,3-diathiazole 5a does this at 140–150 °C and the S2 generated is intercepted with 2,3-diphenylbutadiene, 2,3-dimethylbutadiene and norbornene to give 16a, 16b and 17 respectively.

Hunig’s base and S 2 Cl 2 give the fused 1,4-thiazines 1 and (in the presence of formic acid) 2 and 3, each of which readily extrudes sulfur, selectively and quantitatively, to give the fused pyrroles 4, 5 and 6 respectively; at higher temperatures Hunig’s base and S 2 Cl 2 can be converted into the pyrroles in one pot, and the cycloadducts 8 and 10 are thus readily available in two steps.

Alkenes and alkynes react readily with trithiazyl trichloride 1 to give 1,2,5-thiadiazoles 2 in one step. Thus 3-amino-1,2,5-thiadiazole 5 is now readily available from N-vinylphthalimide and 1 in two steps. Cyclic alkenes react similarly to give fused thiadiazoles (7, 12) and phenanthrene gives the phenanthrothiadiazole 16. Tetra-substituted alkenes such as 13 appear to give the analogous 3,4-dihydrothiadiazoles (e.g. 14) which spontaneously ring open to give readily hydrolysed bis(methyleneamino) sulfides (e.g. 15). A simple set of mechanisms is proposed for all of these reactions.

The reaction of 2,5-diarylfurans with trithiazyl trichloride 1 to give 5-aroyl-3-arylisothiazoles in a useful one-step synthesis of isothiazoles has been extended to both weakly and strongly polarised unsymmetrical 2,5-diarylfurans. These react in an entirely analogous manner; the more electron releasing aryl group becomes incorporated into the 5-aroyl group of the isothiazole as the exclusive (strong polarisation) or the major (weak polarisation) product. However, with 3-bromo-2-(4-methoxyphenyl)-5-(4-nitrophenyl)furan 7, where the more reactive furan β-position is now substituted, this regiospecificity is reversed (to give isothiazole 8). When one of the α-aryl groups in the furan is replaced by methyl the same regiospecific isothiazole formation is now accompanied by some ring and side chain chlorination (15 → 16 + 17 + 18). All of these results can be explained by mechanisms (Schemes 2 and 5) which involve initial electrophilic attack of the furan to give a β-thiazyl derivative. This highly reactive (nitrenoid) substituent then induces a novel opening of the furan ring 21 to give a highly delocalised intermediate 22 which recyclises to the isothiazole.

Activated allylic compounds react with trithiazyl trichloride, (NSCl)3, to give 1,2,5-thiadiazoles 1 and isothiazoles 2. An allylic 2-substituent normally prevents formation of an aromatic 1,2,5-thiadiazole, and isothiazole formation becomes the major pathway. Simple allylic compounds are not very reactive towards (NSCl)3 but a terminal electron withdrawing group (CO2Et) enhances the reactivity. With unsymmetrical allylic compounds, isothiazole formation is regiospecific placing the more electron withdrawing group adjacent to the ring sulfur. 1,3-Diketones give 3-acyl-1,2,5-thiadiazoles; unsymmetrical 1,3-diketones give these thiadiazoles regiospecifically, explicable by cyclisation of an intermediate onto the more reactive carbonyl group. 1,4-Diketones give 3,4-diacyl-1,2,5-thiadiazoles; thus 1,2-dibenzoyl-ethane, -ethene and -ethyne all give 3,4-dibenzoylthiadiazole (40–44%). Many of these trithiazyl trichloride reactions provide attractive one-step routes to 1,2,5-thiadiazoles and isothiazoles.

The reaction of p -benzoquinone-4-oximes with disulfur dichloride affords the red 6 H -1,2,3-benzodithiazol-6-ones. Some ring chlorination occurs, but 2,6-substituents are retained in the products except for a tert -butyl group, which is, exceptionally, replaced by chlorine. 1,4-Naphthoquinone 4-oxime and 1,2-naphthoquinone 2-oxime similarly give the red 4-chloro-5 H -naphtho[1,2- d ][1,2,3]dithiazol-5-one and the blue 9-chloro-4 H -naphtho[2,3- d ][1,2,3]dithiazol-4-one respectively. A unified set of mechanisms is proposed for all of the reactions.

4,5-Dichloro-1,2,3-dithiazolium chloride 1 condenses with active methylene compounds, such as malononitrile, barbituric acid and Meldrum’s acid, to give the dithiazol-5-ylidene derivatives, such as 3, 4 and 5, in modest yields. Better yields are obtained from 4-chloro-1,2,3-dithiazole-5-thione 6. Thus the thione 6 condenses with diphenyldiazomethane in a very mild version of the Barton double extrusion synthesis of hindered alkenes; this requires neither heat to extrude nitrogen nor a phosphine to abstract sulfur, to give the alkene 7 (83%) (Scheme 1). This alkene rearranges at room temperature, with loss of hydrogen chloride and sulfur, to give the benzothiophene 13 (89%) in a new thiophene ring-forming reaction (Scheme 2). The thione 6 also condenses with tetracyanoethylene oxide to give a better yield of the dicyanomethylene compound 3 (70%) (Scheme 4). Compound 3, in turn, reacts with morpholine and with chloride ions (Scheme 5) to give 3-morpholino- 19 (60%) and 3-chloro- 20 (100%) isothiazole-4,5-dicarbonitrile, in a new isothiazole ring synthesis. Mechanisms are proposed for all of these reactions.

Methyl 3-aminocrotonate 7 reacts with 4,5-dichloro-1,2,3-dithiazolium chloride 1 at room temperature to give methyl 5-cyano-3-methylisothiazole-4-carboxylate 9 in high yield (78%) (Schemes 1 and 2). This reaction is formally related to Woodward’s synthesis of methyl 3-methylisothiazole-4-carboxylate 24 from the same enamine and thiophosgene (Scheme 7). 3-Aminocrotononitrile 10 is similarly converted into 4,5-dicyano-3-methylisothiazole 12 but the yield is much reduced (to 40%) since the reaction is more complex (Scheme 3) giving 2,3,5-tricyano-4,6-dimethylpyridine 14 (20%), in a new pyridine ring construction, and three other minor products. All the products can be accounted for by reasonable mechanisms (Schemes 4, 5 and 6). One of the minor products, ketone 13, has been synthesized from the enolate anion 21 and the reagent 1, and the analogous ketones 23 have been readily prepared in high yield from the active methylene compounds 22 and reagent 1.

Primary aromatic amines are readily converted into arylimino-1,2,3-dithiazoles 2 and the derived cyanothioformanilides 6, both of which are rapidly cleaved by ethylmagnesium bromide in hot THF to give the corresponding isothiocyanates. The transformation 2→6→ArNCS can be performed as a ‘one-pot’ operation. The imines 2 are also converted, more slowly, into the isothiocyanates by sodium hydride in hot THF, via the cyanothioformanilides 6. Conversion of the anilides 6 into isothiocyanates is much faster under microwave irradiation in 2,6-lutidine. Mechanisms are proposed for these reactions.

Novel N-arylimino-1,2,3-dithiazole derivatives of aminoquinolines and aminonaphthalenes have been synthesised. The antibacterial and antifungal activities of these compounds were measured; the new dithiazoles are significantly active against fungi, but no enhancement of biological activity was detected by introduction of the more complex aromatic moiety.