Syntheses of heterocyclic compounds—I Cyclization of N-substituted O-nitroanilines

Internal cyclization of a nitrogroup was carried out by heating the N-substituted o-nitroanilines (I; R=C₆H₁₁---, C₆H₅.CH₂, C₆H₅.CH₂.CH₂---, X=NH) in the presence of ferrous oxalate¹ (Waterman and Vivian's method) as a potential route to partly hydrogenated nitrogen heterocycles. A mechanism for this type of ring-closure is proposed.     

Furano compounds—IX

Starting with the appropriate 3-hydroxybenzoxanthones and the following the sequence of reactions allylation, Claisen migration, acetylation, bromine addition and dehydrobromination, 7:8-benzo- and 5:6-benzo-3:4, 2′:3′-furanoxanthones have been synthesized.     

Mass spectrometry of hop compounds—II: Mass spectra of related oxygen heterocyclic compounds

Mass spectra have been determined of a number of phloroglucinol derivatives and closely-related compounds encountered in chemical studies of hop components. Initial fission involving acyl, alkyl or alkenyl side-chains gives predominantly even-electron ions which then fragment their oxygen heterocyclic rings by elimination of neutral molecules, whilst gem-dialkenyl centres show preference for loss of an alkenyl group. The fragment ions induced by electron-impact may be correlated to a useful extent with molecular structure.     

Studies on the syntheses of heterocyclic compounds. CLXXIV. An approach to the synthesis of oxyacanthine and berbamine

Schotten-Baumann reaction of the amine (X) with 4-benzyloxy-3,4′-oxydiphenylacetyl chloride (XI) gave two amides, (XIIa) and (XIIb), which were cyclized to give the corresponding 3,4-dihydroisoquinolines, respectively. Methylation of the above 3,4-dihydro-isoquinolines, followed by hydrolysis, afforded the compounds having the same composition as berbamine (Ia) and oxyacanthine (Ib), whose structures are under examination.     

Studies on organophosphorus compounds—III: Reaction of α-substituted secondary car☐amides with HMPA—amidine and/or nitrile syntheses

Secondary car☐amides (R¹CONHR²) undergo different reactions when heated in HMPA at about 220°. If R¹ or R² can form stable carbonium ions, fragmentation reactions are observed and the corresponding nitriles R²CN or R¹CN, respectively, are formed. Also amidines are produced. N-benzyl-acetamide rearranges when heated in HMPA to give β-phenyl-propionitrile, It is suggested that in all the reactions investigated the first step is the formation of a phosphorodiamidate followed by formation of a nitrilium carbonium ion. The fragmentation reactions can be used as an alternative to the Sandmeyer reaction (nitrile synthesis).     

Mass spectrometry of heterocyclic compounds—II: Electron-impact induced fragmentation of 3,5-diphenyl-1,2,4-oxadiazole

The electron-impact induced fragmentation of 3,5-diphenyl-1,2,4-oxadiazole has been investigated by labelling experiments, defocused metastable ion detections and high resolution mass measurements. The main fragmentation process suggests heterocyclic cleavage at the 1 to 5 and 3 to 4 bonds confirming our previous interpretation. The structure of the major fragment ion [C₇H₅NO]⁺· has been interpreted as being represented by the isomeric benzonitrile oxide and phenylisocyanate structures, the latter isomerising irreversibly from the former. The benzonitrile oxide structure is consistent with [C₇H₅NO]⁺· formation by cleavage of the 1 to 5 and 3 to 4 bonds.     

Heterocyclic fluorine compounds—III Monofluoroxanthones

The four monofluoroxanthones substituted in the benzene ring have been prepared by two different routes, namely by cyclisation of the appropriate carboxyfluorodiphenyl ether and by a Balz-Schiemann reaction with the corresponding aminoxanthone.     

Fragmentation and rearrangement processes in the mass spectra of perhalogenoaromatic compounds—VIII: Fluoroaromatic heterocyclic derivatives of group IV

The metastable ion supported fragmentations and fluorine transfer rearrangements of a series of fluoroaromatic heterocyclic derivatives of silicon, germanium and tin are reported. Of particular interest is the unique loss of neutral SiF₄ from the parent ion of (C₁₂F₈)Si yielding the [C₂₄F₁₂]⁺˙ ion. These and similar rearrangements are discussed and structures are proposed for some of the ions observed. The general case of cyclic rearrangement intermediates prior to the loss of neutral metal fluorides from perfluoroaromatic derivatives is discussed. Losses of neutral metal fluorides from the parent ions appear to involve a species with increased co-ordination number about the central atom as an intermediate. In addition to (C₁₂F₈)₂M, the following compound types were studied: (C₆H₅)₂Ge(C₁₂F₈), (C₁₂F₈S)₂M and R₄Sn₂(C₆F₄)₂ (where M = a Group IV metal and R = CH₃ or C₆H₅).     

Studies on organophosphorus compounds—V: Pyridines from secondary car☐amides and HMPA

A new pyridine synthesis has been found by refluxing certain simple secondary car☐amides in HMPA. Thus 2,6-dimethylpyridine, 2-ethyl-6-methylpyridine, 2,3,6-trimethylpyridine, 2-ethyl-3,6-dimethylpyridine, 2-benzyl-6-methyl-3-phenylpyridine, 2-ethyl-3-methyl-5,6,7,8-tetrahydroquinoline and 2-t-butyl-6-methylpyridine were prepared in 15–40% yield.     

Studies on argentine plants—XX The syntheses of fargarine II

Fagarine II has been synthesized starting from tetrahydropseudoberberine and its proposed structure (V) confirmed.     

Mass spectrometry of heterocyclic compounds—III. Electron-impact-induced fragmentation of 1,2-benzisothiazole and some 3-substituted derivatives

The mass spectra of fifteen 1,2-benzisothiazoles are reported; their fragmentation patterns have been investigated by labelling experiments, high resolution mass measurements and defocused metastable ion detection. The parent compound of the series, 1,2-benzisothiazole, eliminates HCN after partial inter-ring hydrogen scrambling. The extent of scrambling has been determined for normal daughter ions produced at different electron beam energies and also for metastable daughter ions, and is compared with the data reported for benzothiazole. Some 3-substituted derivatives show unusual fragmentation patterns. The mechanisms of these processes are under further investigation.     

Studies on the syntheses of heterocyclic compounds. part CCLXXIX . Synthesis of O-isobutylcularidine

Although various methods of oxepine formation from phenoxybenzene dicarboxylic acids was attempted, only 11-hydroxy-4-isobutoxy-7,8-dimethoxydibenz[b,f]oxepin-l-ylaeetic acid lactone (XXX) was synthesized successfully. Compound XXX gave O-isobutylcularidine (XXXVlIb) in a few steps. Our synthetic O-isobutylcularidine was identical with that prepared from natural cularidine proving the structure for cularidine proposed by Manske. However, dealkylation of synthetic O-isobutylcularidine was unsuccessful.     

Studies of intramolecular alkylidene carbene reactions; an approach to heterocyclic nucleoside bases

A series of investigations into the applications of intramolecular cyclisations of alkylidene carbenes are described. The insertion reaction of the carbene generated from 1,4-di(tert-butyldimethylsilyloxy)-3-benzyloxy-butane-2-one to the benzylic position proceeded in good yield and a diastereoselectivity of 3.6:1. The corresponding insertion process of 1,4-di(tert-butyldimethylsilyloxy)-3-methyloxymethyl-butane-2-one gave a mixture of products, including one resulting from a competitive trapping of the carbene by the oxygen atom of a silyloxy group.     

Organic fluorine compounds—XXXVIII N-alkylated fluoroamino acids

Hydroxyproline methyl ester was methylated and the hydroxyl group of the product replaced by fluorine, using 1,1,2-trifluoro-2-chloroethyl-diethylamine. Analogously, the N,N-dimethyl derivatives of several β-hydroxy--amino acids were transformed into the corresponding β-fluoro compounds.     

Fragmentation and rearrangement processes in the mass spectra of perhalogenoaromatic compounds—VI. Perfluoroaromatic heterocyclic derivatives of sulfur,selenium and tellurium

The mass spectra of the compounds C₁₂F₈M₂ (M = S, Se), (I), C₁₂F₈M (M = S, Se, Te), (II) and C₁₂F₈SX₂ (X = Br, I), (III), have been measured. Results indicate that sulfur-carbon bonds are more stable under electron bombardment than either selenium-carbon or tellurium-carbon bonds. Numerous metastable-supported transitions are evident, which are incorporated into comprehensive fragmentation schemes for these compounds. Many metastable transitions, not previously reported, were observed for the fluorocarbon fragments and a fragmentation scheme is reported. The bromine and iodine-containing compounds behave remarkably like the heterocyclic systems, I and II, presumably due to initial loss of Br₂ or I₂ to form a ring system of type II.     

Studies on the syntheses of heterocyclic compounds—DLXIX : One-step synthesis of dihydropyridocarbazole derivatives

Heating indole and 4,5-dibromomethyl-3-hydroxy-2-methylpyridine hydrobromide (10), followed by acetylation, gave the desired dihydropyrido[4.3-b]carbazole (12) and its structural isomer, dihydropyrido[3.4-b]carbazole (13). The structures of (12 and 13) were determined by UV spectral investigations of the corresponding dehydrogenated products, 4-acetoxy-3-methyl-6H-pyrido[4.3-b]carbazole (11) and 4-acetoxy-3-methyl-10H-pyrido[3.4-b]carbazole (14).On the other hand, the same reaction in the presence of sodium iodide afforded 12 together with four other coupling products which were not cyclized, such as (16, 17, 18), and a dimer.     

Studies on organophosphorus compounds—IV: HMPA as precursor for dimethylamine in nucleophilic aromatic substitution reactions

The potential leaving groups (NO₂, Cl, Br, OH, OMe) in nucleophilic aromatic substitution reactions are replaced by a dimethylamino group simply by heating the aromatic compounds (activated by cyano- or nitro-groups) in HMPA at elevated temperature.     

Synthetic studies leading to DE-ring analogs of camptothecin

A synthetic scheme leading to an isomeric DE ring ( 14 ) of the anti-tumor alkaloid, camptothecin, has been achieved. However, the method failed to give the correct pyridone lactone ( 2 ) found in this alkaloid.