The 2H-Benzimidazoles (Isobenzimidazoles) as Synthons in Heterocyclic Chemistry

This article reviews for the first time the chemistry of isobenzimidazoles (2H-benzimidazoles) with special emphasis on their synthetic application in organic chemistry, Same ideas for future work in this area are outlined

Studies in isothiazole chemistry: I. isothiazolo [5,4-b] pyridines. II. approaches to isothiazolynes

The first part of this thesis describes investigations on the synthesis and chemistry of isothiazolo[5,4-b] pyridines. The syntheses of a number of alkyl isothiazolo[5,4-b] pyridines from 5-amino-3-methylisothiazole under conditions of the Skraup reaction are described and their nuclear magnetic resonance spectra are discussed. The reactions of 3-methyl- and 3,6-dimethylisothiazolo[5,4-b] pyridine have been studied. In particular they did not undergo nitration under the conditions employed and whereas the 3-methyl compound did not condense with benzaldehyde, 3,6-dimethylisothiazolo[5,4-b] pyridine gave mono-styryl products with benzaldehyde, and p-nitrobenzaldehyde. Potassium permanganate oxidation gave isothiazolo[5,4-b] pyrid-3(2H)-one 1,1-dioxides rather than the expected isothiazolo[5,4-b] pyridine carboxylic acids and chromic acid oxidation resulted in cleavage of the isothiazole ring to give 2,3-disubstituted pyridines. Ethyl 4-hydroxy-3-methylisothiazolo[5,4-b] pyridine-5-earboxylabe was readily obtained by thermal cyclisation of the malonate from 5-amino-3-methylisothiazole and ethoxymethylenemalonic ester. The hydroxyl ester was converted to a number of substituted isothiazolo[5,4-b] pyridines. In addition it has been established that methylation at nitrogen rather than oxygen occurs with both the 4-hydroxy ester and the 4-hydroxy compound which has been shown to exist preferentially in the carbonyl form, namely 3-methylisothiazolo[5,4-b] _7pyrid-4-one. The reaction of 5-amino-3-methylisothiazole with ethylacetoacetate and with acetylacetone under the conditions of the Conrad Limpach reaction and the Combes reaction respectively, did not give isothiazolo[5,4-b] pyridines. The latter gave a product which has been tentatively formulated as 5-acetyl-3,4-dimethylisothiazole. The second part of this work describes the synthesis of 5-amino-3-chloroisothiazole-4-carboxylic acid, 4-amino-3-methylisothiazole- 5-carboxylic acid and 4-aminoisothiazole-3-carboxylic acid and experiments aimed at investigating the possible intermediacy of isothiazolynes. Attempts to generate and trap isothiazolynes by their aprotic diazotisation with isoainyl nitrite in the presence of 2,3,4,5-tetraphenylcyclopentadienone gave only small quantities of isothiazoles in addition to a variety of oxidation products derived from the arynophile. 4-Amino3-methylisothiazole-5-carboxylic acid gave isothiazolyl-substituted products when furan and anthracene were used as trapping agents, and it was found that the reaction of isothiazole-4-diazonium carboxylate hydrochloride and propylene oxide in the presence of furan gave 4,-cyano-1,2,3-thiadiazole. In none of the reactions investigated was there any evidence for the formation of inothiazolyne intermediates

REDUCTIVE CYCLIZATIONS BY MEANS OF SODIUM BOROHYDRIDE AND PALLADIUM-CHARCOAL

In the course of his investigations into the syntheses of hydroxamic acids Coutts became involved in a study of the reducing properties of sodium borohydride in the presence of palladium-charcoal. The purpose of this thesis is to determine whether it is possible to extend this study to the preparation of novel heterocyclic N-hydroxy compounds. The emphasis of Coutts' studies to date has been on the preparation of cyclic hydroxamic acids, compounds which have aroused interest only in recent years. In 1943, White (1) discovered that the filtrate from cultures of certain strains of Aspergillus flavus possessed antibacterial activity against various gram negative and gram positive bacteria. Further investigation (2) attributed this action to a metabolite, aspergillic acid (I), which was isolated from the filtrate

Synthesis and reactions of Janus-type bis(NHCs), tuned by phosphorus bridges

Due to our first attempts to synthesize P-functional bis(NHCs),[6] we were aware of a problem if bis(thiones) were used. Therefore, the idea emerged to use bis(selones) instead. Herein, the synthesis of the first tricyclic bis(selones) and their conversion to bis(NHCs) having two facially opposed imidazole-2-ylidenes with two linking phosphorus centers in different oxidation states is presented. Furthermore, the formation of homo-bimetallic metal(I) complexes of these NHCs as well as reactions with reducing agents are reported

New Synthetic Tools in the Pyridine, Quinoline and Other Nitrogen-Heterocyclic Series

The halogen-metal interconversion reaction now makes possible the preparation of hitherto difficultly or completely inaccessible organolithium compounds from the corresponding bromo- or iodo-nuclear substituted nitrogen heterocycles by means of other organolithium compounds like n-propyllithium and n-butyllithium : C5H4NBr +n-C4H9Li ( 3-bromopyridine) → C5H4NLi +n-C4H9Br ( 3-pyridyllithium). These organolithium compounds of the nitrogen heterocycles are of a relatively high order of reactivity with other functional groups. Some of the types reported on in the pyridine series are: 1. 3-pyridyllithium in 70 per cent yield from 3-bromopyridine and n-butyllithium, 2. 3-quinolyllithium in 52 per cent yield from 3-bromopyridine, 3. 5-bromo-3-pyridyllithium in 41 per cent yield from 3, 5-dibromopyridine and slightly more than two equivalents of n-butyllithium. In the carbazole series, some of the organolithium compounds rep0rted are: 1. N-ethyl-2, 8-dilithiocarbazole in 84-91 per cent yield from N-ethyl-2, 8-dibromocarbazole, and in 79-92 per cent yield from the corresponding di-iodo-compound. 2. N-ethyl-2-lithiocarbazole 1 from the corresponding iodocarbazole in 68 per cent yield

Studies in new nitrogen-containing heterocyclic compounds

I. QUININDINES AND PYRINDINES: Introduction and Discussion; Discussion of Experimental; Experimental .II. INDENOIMIDAZOLES AND REDUCTION OF AZO-COMPOUNDS BY HYDRAZINE: Introduction and Discussion; Experimenta

8-Hydroxyisoquinolines

Petaline, an alkaloid from Leontice leontopetalum, Linn, has been shown by synthetic and degradative experiments to be a 2,2-dimethyl-8-hydroxy-7-methoxy-1-(p-methoxybenzyl)-1,2,3,4-tetrahydroisoquinolinium salt and is the first benzyl-isoquinoline alkaloid reported with this oxygenation pattern