THE CHEMISTRY OF HALOGENOAZINES ESPECIALLY AS PRECURSORS TO HETEROCYCLIC COMPOUNDS

Mohamad  M. ABDUL‑GHANI

The work presented in this thesis is concerned mainly with an investigation of reactions of the dichloroazine CF₃ CCL=NN=CCICF₃ (7) with a wide range of reagents.The reaction of azine (7) with amines generally gives the monosubstituted product (1:2 molar ratio) and the disubstituted product (1:≥4 molar ratio). The reaction of azine (7) with ammonia (1:2 and 1:7.5 molar ratios), aniline (1:2), methylamine (1:2 and 1:6), methyl glycinate (1:4), ethyl glycinate (1:8), hydroxylamine (1:4) and hydrazine (1:3.5) affords, respectively, the (ZZ)‑ monoaminoazine (118), the (ZZ)‑diaminoazine (92), the monoanilino compound (120) present as the syn (Z) ‑ and anti (E) ‑isomers of the imidoyl tautomer, the (ZZ)‑mono (methylamino) azine (121), the (ZZ)-bis (methylamino) azine (122), the mono‑(ZZ)‑ and (ZE) ‑ (125) and (127) and the di‑(ZZ)‑(126) and (128) substituted glycine esters, the syn  (Z)‑oxime (13) and the dihydro‑s‑tetrazine (131).

A general route to 4‑substituted‑ 1,2,4‑triazoles is established by thermolysis of di‑substituted primary amino azine derivatives. Hydrolysis of the ammonium triazolide (93) with aqueous hydrochloric acid (4M) gives the parent H‑1,2,4‑triazole (81) (75%),which is stable when subjected to oxidizing conditions in an attempt to prepare the N‑hydroxyt riazole. The H‑triazole (81) with its three nitrogens is a nucleophilic species and it undergoes addition reactions at elevated temperatures (120‑150 C) with a variety of unsaturated systems to give exclusively N‑1 substituted triazoles confirming the greater nucleophilicity of the N‑N linkage compared to N‑4.

The sodium salt (182) of the H‑triazole (81) is a nucleophilic species that will displace a leaving group on an electrophilic carbon such as that in alkyl halides giving exclusively N‑1 substituted triazoles. Reaction with ethyl bromoacetate, allyl chloride, propargyl bromide, n‑bromobutane and 4‑bromobut‑l‑ene affords the substitution products (183) to (188), respectively; the propargyl bromide reaction also gives the allenic isomer (186). The reaction with pentafluoropyridine affords the 4‑, 2‑ and 2,4‑substituted fluoropyridyl compounds (189) to (191), respectively. Exposure of a mixture of the azine (7) and triethylamine (1:2 molar ratio) to daylight gives the decatriene (197) as a major product together with trifluoroacetonitrile and tar.

Thermal  1,3‑diplor cycloaddition reactions (20‑100 C) of the dichloroazine (7) with indene, norbornadiene, cyclopentene, cyclopentadiene, dicyclopentadiene, 2,3‑dihydrofuran, 2,3‑dihydropyran, acenaphthalene and cycloheptene give in each case as the major product, the rearranged (3+2) cycloadducts (271) to (280) containing a CF₃ CCl₂ group; hydrolysis of the CF₃ CCl₂ group to CF₃ CO giving amides (281) to (290) takes place on attempted  chromatographic purification on silica gel.

Elimination of the trifluoroacetyl group from amides of type (260) is achieved by treatment with an ethanolic solution of methylamine. Treatment of the indene (281) and the norbornadiene (282)+(283) cycloaddition products afford the parent N‑H compounds (332) and (335a)+(335b) together with N‑methyltrifluoroacetamide. Under apparently similar conditions the norbornadiene cycloaddition product (282) gives the formamide (334)(87%) and the iminoindazole (336) (5%).