Novel cycloadducts from the 1,3-dipolar cycloaddition reactions of triazolium-1-imide 1,3-dipoles

A range of imidazo-1,2,3-triazoles were synthesised by the 1,3-dipolar cycloaddition of triazolium-1-imides with N-sulfonyl imines. Oxazolo-1,2,3-triazoles were identified as side products of this reaction. Benzyne was also used as a 1,3-dipolarophile in the cycloaddition reaction, resulting in a range of tricyclic triazoloindoles


Introduction
In work previously carried out by our group 3a,6a-diaryl hexahydropyrrolotriazoles 3 underwent photoinduced disrotatory ring expansion to the new 2,5,6,7-tetrahydro-1,2,3,5 tetrazocines 4 1 (Scheme 1).Of key importance in the stability of these tetrazocines was the saturation of the C-6 position, and the nature of the group attached to C-6.Both saturation and electron withdrawing groups were found to initiate rearrangement of the initially formed tetrazocine, by the attack of N-2 on C-6.In searching for new ring systems of this type, and in particular those with a fifth nitrogen in the system, the cycloadditions of triazolium-1-imides 1 with various dipolarophiles were investigated.

Results and Discussion
Benzyne as a Dipolarophile.The use of benzyne 5 as a dipolarophile in the cycloaddition with triazolium-1-imide 1 would provide a degree of unsaturation between C-4a and C-8a in the cycloadduct 3 (Scheme 2).Subsequent photochemical induced ring opening would produce a 1,2,3,5-tetrazocine 4 with a C-5a-C-9a double bond, but attack by N-2 on a closed aromatic sextet of electrons would be a highly unfavourable process.
In situ formation of benzyne through diazotisation of anthranilic acid 6 and isoamylnitrite in 1,2-dimethoxyethane with the 1,3-dipole 1a,b yielded the cycloadducts 3a,b.Reaction conditions were optimised by heating a stirred solution of the 1,3-dipole at the reflux temperature of the solvent, thereby increasing the reactivity of the dipole within the short transitory lifetime of benzyne.Similarly, it was observed that yields were maximised by simultaneous addition of solvent solutions of anthranilic acid and isoamylnitrite every five minutes in 2cm 3 aliquots.
Yields of the cycloadduct were increased by introducing a para nitro-group on the phenyl ring of the nitrogen terminus of the 1,3-dipole.

N-Sulfonyl imines as dipolarophiles.
Previously the only carbon and nitrogen-containing dipolarophiles that had been successfully used in the cycloaddition to triazolium-1-imides were isocyanates and isothiocyanates. 2,3owever the use of these dipolarophiles limit the substituent at C-5 to carbonyl and thiocarbonyl groups.In order to enable variation of the substituent at C-5 a different nitrogen-containing dipolarophile was required.N-sulfonyl imines have been increasing in importance because they are one of the few types of electron-deficient imines that are stable enough to be isolated but reactive enough to undergo addition reactions.They have been used as electron-deficient 1,3-azabutadiene equivalents in inverse electron demand Diels-Alder chemistry, 4 as electrophilic aza-aldehyde equivalents in addition reactions, 5 as reactive olefin equivalents in ene reactions, 6 and as precursors to Nsulfonyloxaziridines which have utility as chiral oxidants. 7It was decided to investigate if Nsulfonyl imines could be used in the 1,3-dipolar cycloaddition with triazolium-1-imides.
Conjugation with electron-withdrawing or electron-releasing substituents increases the dipolarophilic activity of a multiple bond.Sulfonyl imines containing an aromatic group do not form adducts when heated in benzene with dienes, despite the electron-withdrawing effect of the sulfonyl group.However, if the carbon atom of the C=N bond also carries an electronwithdrawing group as in CO 2 R, CF 3 or CCl 3 , adducts are formed under the above conditions. 8our imines 7a-d were chosen to use as dipolarophiles in the cycloaddition reaction.Of these, three had an electron-withdrawing group 7a-c attached to the carbon, i.e.CO 2 CH 3 , CO 2 C 2 H 5 , CCl 3 , and the fourth 7d had a phenyl group attached to the carbon atom.As expected the Nsulfonyl benzaldimine failed to give the required imidazo-1,2,3-triazole.The N-sulfonyl trichloroimine 7c also failed to give the required adduct.However both of the N-sulfonyl imino acetic acid esters 7a,b successfully added to the triazolium-1-imide 1a-d to give the novel imidazo-1,2,3-triazoles 8a-e with a saturated C-5 position (Scheme 3).The success of the addition of the imino acetic acid esters is thought to be due to favourable secondary orbital interactions in the transition state, due to the conjugation of the π-system.

Table 1 .
Yields and melting points of the novel imidazo-1,2,3-triazoles and oxazolo-1,2,3triazoles 11neral Procedures.Infrared spectra were measured on a Perkin-Elmer System 2000 FT-IR.NMR spectra were recorded on a Bruker 400MHz spectrometer.Melting points were recorded on a Griffin apparatus and are uncorrected.Microanalytical data was provided by the Chemistry Department in University College, Dublin.The synthesis of all dipoles 2,10 and dipolarophiles11was carried out as described previously.