The electrophilic substitution of N-alkylated isocarbostyrils was examined in considerable detail. Bromination, acylation, nitration, and acid-catalyzed condensation with formaldehyde occurred exclusively at C-4 under relatively mild conditions. The acylation of isocarbostyrils has heretofore not been reported.The bromination of 2-methyl-5-nitroisocarbostyril in aqueous acetic acid gave 2-methyl-3,4-dihydro-3-hydroxy-4-bromo-5-nitroisocarbostyril (7) of unknown stereochemistry, as the sole product. When heated above its melting point, 7 lost the elements of water to give the "normal" product of bromination 8.In aqueous acetic acid, excess bromine was shown to convert isocarbostyrils to the corresponding 3,4-dihydro-3-hydroxy-4,4-dibromo derivatives whose structures were supported by spectral and degradative evidence.
It is shoun that the sodium hydride (in dilnethyl formamide) induced elimination of hydrogen bromide from 1,3-dibromo-2-(tetrahydropyran-2-y1oxy)propane (3) can be considered to r e s~~l t in the in situ formation of 3-bronio-2-(tetrahydropyran-2-y1oxy)propene (4). When generated in this manner, 4 was shown to function as a masked acetonyl bromide of considerable utility. Under similar conditions, 1,3-dibrorno-2-methoxypropane was assumed to produce 3-bromo-2-methoxypropene, which also was shown to be a useful masked acetonyl bromide.The pyrolytic elimination of methanol from bromoacetone dimethyl ketal was shown to produce a 1 :1 mixture of the two possible isomeric en01 ethers, rather than pure 3-bromo-2-methoxypropene as stated in the literature (2).
NOTES 3079 N-(2,5-Dihydroxy-4-methoxyphenethyl) formamide (6d)Quinone 5d (1.0 g) was dissolved in 30 ml of methanol and hydrogenated in a Brown hydrogenator with 100 mg of 10% Pd-C catalyst. Hydrogen uptake ceased after 10 min. The mixture was stirred 20 min longer and then it was filtered over a bed of filter aid. Evaporation and recrystallization of the solid residue from 3 ml of methanol and 10 ml of ethyl acetate yielded 600 mg of tan-colored, i.e. air sensitive crystals, m.p. 129-131". This material was analyzed without further purification: I,,, (EtOH) 6-Hydroxydopamine Hydrobromide (7)( a ) From 2,5-Dihydroxy-4-methoxyphenethylamine Acetate (6a. HOAc) Compound 6a (1 1.5 g, 0.0473 mol) was refluxed for 5 h in 62.5 ml of 48% hydrobromic acid under nitrogen. The light brown reaction mixture was seeded, cooled to O0, filtered, washed with three 20 ml-portions of isopropanol followed by three 20 ml-portions of hexane. After drying in vacuo the white, crystalline 6-hydroxydopamine hydrobromide (7) inlet, was placed 5.04 g (0.0224 mol) of 6c and 10 ml of 48% hydrobromic acid. After refluxing for 4 h under nitrogen, the brown reaction mixture was evaporated with a rotary evaporator. The brown crystals were slurried with isopropanol, filtered, and washed with the same solvent to give 2.16 g (31%) of tan-colored 7 which was identical (i.r. and t.1.c.) with the material obtained in section a .
The addition of bromine to 2,2-diphenyl-4-pentenylan~ine ( 8 0 ) resulted in the formation of 2-bromomethyl-4,4-diphenylpyrrolidine hydrobromide (IOn), the structure of which was established by its mass spectrum and other properties. Analogous products were obtained from the corresponding methyl secondary amine and two methyl-substituted primary amines.The bromomethylpyrrolidines IOa and 10c gave the aziridines I l n a n d I l b on treatment with sodium hydride in DMF. D r y hydrogen bromide converted the unsubstituted aziridine l l a to 3,3-diphenyl-5-bromopiperidine hydrobromide ( 1 2 0 ) . Liberation of the methyl substituted bromomethylpyrrolidine l o b from the hydrobromide salt resulted in the spontaneous transformation to a single 2-methyl-3-bromopiperidine (12b) of unestablished stereochemistry.L'addition d u brome sur la diphinyl-2,2 penttnyl-4 nmine (80) conduit au bromhydrate de la brornomCthy1-2 diphenyl-4,4 pyrrolidine (Ion) dont la structtire a CtC dCterminCe par spectrometric de masse ainsi que par d'aulres propri6tCs. Des produits analogues ont ttC obtenus h partir d e la methylamine secondail'e correspondante ainsi que de deux amines primaires substituCes par des groupes mithyles.Les bromomCthylpyrrolidines Ion et 10c par traitement avec de I'hydrure de sodium dans le DMF conduisent aux aziridines l l a et l l b . L'acide bromhydrique sec transforme l'aziridine non-substitut 1 l a en brornhydrate de diphenyl-3,3 bromo-5 pipiridhe ( 1 2 a ) . L a neutralisation de l'acide bromhydrique libtre la bromom6thylpyrrolidine substituC p a r un groupe mCthyle ( l o b ) qui se transforme spontanement en une seule mCthyl-2 bromo-3 piphidine (120) de sttrCochin1ie non dCterminCe.[Traduit par le journal] Can. J. Chem., 52, 1321 (1974) The first intramolecular haloamination reactions were carried out almost a century ago by Ladenburg (1,2) and Merling (3) but the structures of the products were not assigned correctly until 1900. At that time Willstatter (4) demonstrated that the zinc and hydroiodic acid reduction of the products obtained from dimethylamino-4-pentene (1, R' = R2 = CH,) and bromine or iodine gave 1,1,2-trimethylpy~rolidinium iodide (3, R' = R' = CH3). The five-membered further until 1962. In connection with their interest in the kinetics of the iodocyclization of various unsaturated systems, Shilov and coworkers (5) reported that primary as well as tertiary 4-pentenyl amines underwent the cyclization reaction. Subsequent publications (6-8) from that laboratory were devoted t o a further elaboration of the mechanism and the generality of the r e a~t i o n .~ In all cases the products were assigned five-membered cyclic structures (2), presumably on the basis of Willstatter's observation and by mechanistic analogy to other halocyclization reactions (9).3In relation to studies (14,15) concerning 'The existence of this reaction has evidently not been generally recognized in the chemical literature of the western world. Recent standard (!) reference texts (10-13) state only that, depending o n the ...
A description of the synthesis of epoxides from diary1 ketones and dimethylsulfonium methylide by a modified technique is given.The nuclear magnetic resonance spectra of several of the 11-substituted dibenzo[b,e]azepin-6-ones are interpreted on the basis of a slow interconversion between diastereomeric boat conformers in which the C-11 substituent is quasi axial or quasi equatorial.
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