A series of N-unsubstituted 1,2,4-triazol-3-ylpyridines was prepared for antiarthritic testing. Weak and scattered antiinflammatory activity was observed, with no clear structure-activity relationships. Some of the compounds, notably the 5-pyridyl-1,2,4-triazole-3-carboxylic acids, showed infrared bands characteristic of strong hydrogen bonding.

Acetals of N-unsubstituted 1,2,4-triazole-3-aldehydes have been prepared by condensation of imidic esters with dimethoxyacethydrazide. Free aldehydes couId not be isolated on hydrolysis of the acetals, or on oxidation of propenyl-l,2,4-triazoles. Condensation of imidic esters and acid hydrazides is satisfactory for the preparation of bitriazolyls and methoxymethyl-and cyanomethyl-1,2,4-triazoles.THE preparation of 1,5-diaryl-l,2,Ptriazole-3-aldehydes from the corresponding esters or acid hydrazides (Part VI *) is not a general method. Although the Sawdey rearrangement which has been used to obtain the esters and hydrazides is limited to the synthesis of derivatives of 1,5-diaryl-l,2,4-triazoles, the preparation of l-p-chlorophenyl-5-methyl-l,2,Ptriazole-3-aldehyde (I ; X = CHO) illustrates a convenient synthetic route in some cases. In the reaction illustrated conversion of the ethoxycarbonyl into the aldehyde group by way of an alcohol group follows normal routine.

Cyclic hemiaminal formation in solid X-unsubstituted azole aldehydes seems to be a general phenomenon when stabilization factors and position of substitution are favourable. Previously reported for 5- substituted 1,2,4-triazole-3-carbaldehydes and benzimidazole-2- carbaldehyde, it has been found to occur also in some previously undescribed aldehydes of pyrazole, imidazole, 3H-imidazo[4,5- b]pyridine, 3H-imidazo[4,5-c]pyridine, and purine. In purine-8- carbaldehyde the hemiaminal may be accompanied by the aldehyde hydrate. P.m.r. studies of the dimers, and of the dipiperidino cyclic aminals derived from them, indicate that in some cases more than one isomeric form is present.

Derivatives of two new diannulated azecine systems have been prepared by ring degradation of precursor bases with cyanogen -bromide-induced solvolysis. Reaction of a tetrahydro-5H-benzo[h] thieno [2,3,-a] quinolizine (5a) and a tetrahydro-7H-benzo[h][1] benzothieno [2,3-a] quinolizine (5b) with cyanogen bromide and magnesium oxide under solvolytic conditions yielded derivatives of a hexahydrobenzo [d] thieno [2,3-g] azecine (6a) and a hexahydrobenzo [d][1] benzothieno [2,3-g] azecine (6b), respectively. Functional group interconversions of these medium-ring systems were performed, including oxidations to cyclic ketones. The 5H-benzo[h] thieno [2,3-a] quinolizine and 7H-benzo[h] [l] benzothieno [2,3-a] quinolizine bases (5a) and (5b) are the first reported examples of these ring systems.

Four 5-aryl-2,3-dihydro-1,4-benzoxazepines (5a-d), with electron-releasing substituents, were prepared by a Bischler-Napieralski-type reaction of N-(2-aryloxyethyl)benzamides with phosphorus oxychloride in butanenitrile or ethanenitrile. Analogous 2,3-dihydro-1,4-benzoxazepines (12a, b), with hydrogen only or a chlorine substituent in the fused aromatic ring, were prepared by C-N ring-closure reactions. Cyclization of a dilute solution of N-[3-(3-methoxyphenoxy)propyl]benzamide (21) with phosphorus oxychloride in ethanenitrile gave a 40% yield of 9-methoxy-6-phenyl-3,4-dihydro- 2H-1,5-benzoxazocine (22). The seven- and eight-membered cyclic imines were converted into their methiodide salts (6a-d), (15a,b) and (24). These were reduced with sodium tetrahydroborate to yield the 5-aryl-4-methyl-2,3,4,5-tetrahydro-1,4-benzoxazepines (7a-d) and (l6a,b), and the 9-methoxy- 5-methyl-6-phenyl-3,4,5,6-tetrahydro-2H-1,5-benzoxazocine (25). These products were prepared for use as starting materials in ring-expansion reactions through the Meisenheimer rearrangement.