Amines from cyclization

The benzazepines, veri 1 opam (79) and anilopam (81), for example, represent significant departures from the above generalization. Construction of the former starts with the alkylation of veratrylamine (74) with the dimethyl acetal of bromoacetaldehyde to give the secondary amine 7, Cyclization under acidic conditions leads to the benzazepine... 

The ureas, e.g. 28 (R = NMe2), derived from the corresponding 2-(l-arylviny )benzylamines by reaction with (dimethylamino)carbamoyl chloride (Me2NCOCl) in the presence of triethyl-amine, undergo cyclization in refluxing phosphoryl chloride to the 5-aryl-3-(dimethylamino)-l//-2-benzazepin-3-amines. e.g. 29a.84 Prepared similarly are the 3-(4-methylpiperazin-l-yl) compound 29b and the 3-methyl derivative 29c from the corresponding urea and amide, respectively. 

Some functionalized thiophenes have been investigated in order to assess the scope of ylide-derived chemistry. As already mentioned, 2-(hydroxymethyl)thiophene still gives the S-ylide upon Rh2(OAe)4-catalyzed reaction with dimethyl diazomalonate 146 but O/H insertion instead of ylide formation seems to have been observed by other workers (Footnote 4 in Ref. 2S4)). From the room temperature reaction of 2-(aminomethyl)thiophene and dimethyl diazomalonate, however, salt 271 was isolated quite unexpectedly 254). Rh2(OAc)4, perhaps deactivated by the substrate, is useless in terms of the anticipated earbenoid reactions. Formation of a diazo-malonic ester amide and amine-catalyzed cyclization to a 5-hydroxytriazole seem to take place instead. 

The hydrated dihydropyrimidotriazines 323 were prepared from the pyrimidine 321 by sequential amination and cyclization or by sequential amination, acylation, and cyclization [80JCR(S)278], Thus, acylhydra-zines reacted with pyrimidine 321 to give acylhydrazinopyrimidines 322, which then were cyclized by treatment with aqueous sodium hydrosulfite to give 323. They were found to be inactive as enzyme inhibitors. 

A related amination/rearrangement/cyclization tandem sequence had been introduced by Cossy [49]. Starting from cyclic epoxyketones 224 the reaction with propargylamines 225 caused an oxirane-opening condensation process to generate the enaminoketones 226. Upon heating in toluene to reflux, aza-Claisen rearrangement delivered the intermediate allenyl imines 227, which... 

Piperidones of two types have been prepared from saccharide derivatives. Those of one type are lactams, exemplified by 187, obtained by oxidizing255 5-azido-5-deoxy-2,3-0-isopropyidene-/3-D-ribo-furanose (185) to 186, reducing the lactone 186 to the amine, and cyclizing this to 187. The other type comprises the 4-piperidones such as 189 this is obtained256 by oxidizing methyl a-D-arabinopyrano-side (188) with periodate, and treating the product with methylamine and 3-oxopentanedioic acid the bicyclic compound obtained from the a-glycoside differs from that from the /3 anomer. 

Macrocyclic derivatives are of considerable importance in biological areas and as complexing agents, particularly for metals. Macrocyclic examples are given in MACROLIDES FROM CYCLIZATION OF w-BROMOCARBOXYLIC ACIDS 11-HYDROXYUNDECANOIC LACTONE and MACROCYCLIC POLY AMINES 1,4,7,10,13,16-HEX AAZ ACYCLOOCT ADE-... 

Two closely related mesoionic systems, 59 and 60, were obtained by reductive cyclization of 61 with TEP,62 and by oxidation of 62 with lead tetraacetate,63 respectively. The pyrazolo[4,3-c]pyrazole 64 was obtained from the azo compound 63 by reduction with dithionite, followed by diazotization of the resultant amine and cyclization with... 

Unsymmetrical secondary and tertiary amines. Unsymmetrical amines are obtained in 50-95% yield by reaction of an alcohol and amine in the presence of this ruthenium catalyst. The intramolecular version of this reaction provides an efficient synthesis of cyclic amines either from oc,a>-amino alcohols and an alcohol or from a,tu-diols and an amine. The cyclization is useful for preparation of tetrahydroiso-quinolines.3... 

Several novel IOji bicyclic imidazoles (63 or 65), obtained from polysubstituted imidazoles, were reported during this period. The first synthesis of an imidazo[4 ,5 4,5]thieno[3,2-d]pyri-midine commences with l-benzyl-2-(methylthio)-4-bromo-5-cyanoimidazole (62) [95TL12807]. Sequential metallation, sulfurization, S-alkyiation, and Thorpe cyclization of 62 afforded the thienoimidazole intermediate 63. Precursor 62 was obtained from 1 -benzyl-2,4,5-tribromoimida-zole in a series of metallation-electrophile trapping protocols. Nitroimidazo[l,5-a]imidazoles (65) were readily obtained from l-(acylmethyl)-2-methyl-4-nitro-5-bromoimidazoles (64) by sequential amination and cyclization [94KGS490]. 

An advantage of this methodology is that a strained or complicated molecule of the natural alkaloids can be built from simple compounds, such as commercially available carboxylic acids or amines, from which enamides are prepared. In addition, on cyclization, the skeletons of complex polycyclic and multifunctionalized natural products or their precursors, which are easily converted to the target alkaloids, can be formed in one step. 

Oxazoloquinolines were obtained from 2-amino-3-bromoquinolines by successive acylation, amination, and cyclization <03S2033>. 

Chloroquinoxaline undergoes facile nucleophilic displacement reactions with amines and aryloxides to give the corresponding 2-substituted quinoxalines. With diamines, besides the 2-amino derivatives, bis(quinoxalinyl)alkylenediamines are produced. When 2-chloro-quinoxaline is treated with a sodium aryloxide in an excess of the corresponding phenol, a mixture of the expected 2-aryloxyquinoxaline and the corresponding benzofuro[2,3-6]quinoxaline (144) is obtained. 2-Aryloxyquinoxalines are readily cyclized with polyphosphoric acid to benzofuro[2,3-6]quinoxalines. 2-Arylfuro[2,3-h]quinoxalines (146) result from cyclization of 2-phenacyl-3-quinoxalinones (145). ... 

This ring is formed in high yield from a mercapto-amine and either phosgene or disuccinimido carbonate (see Section 1.3). Ethyl potassium xanthate is also effective [3038]. An aminophenol in which the hydroxy group is masked as its dimethyl aminothiocarbamate cyclizes under conditions which generate the amine from the nitro group. The product is the result of a Newman-Kwart rearrangement [B-40, Vol. 3, p. II). 

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