Azocine synthesis

Perhaps the commonest ring expansion method of azocine synthesis is by Beckmann or Beckmann-type rearrangements of cycloheptanone... 

Azocine, 1-benzoyloctahydro-microbiological oxidation, 7, 658 Azocine, dihydro-, 7, 660-662 Azocine, 1,2-dihydro-synthesis, 7, 660... 

Azocine, dihydromethoxydimethyl-synthesis, 7, 661 Azocine, methoxy-reactions, 7, 664 Azocine, 2-methoxy-synthesis, 7, 663 Azocine, octahydro-drugs, 7, 655... 

Azocin-2( 1H )-one, hexahydro- 1-phenyl-photochemical rearrangement, 7, 656 Azodn-2( 1H )-one, 1,2,7,8-tetrahydro-synthesis, 7, 662 Azocin-5-one IR spectra, 7, 16 transannular interactions, 7, 14 Azocin-5-one, l-(2,4-dimethylphenyl)-IR spectrum, 7, 657 Azocin-5-one, methoxycarbonyl-synthesis, 7, 657 Azocin-5-one, 1-methyl-IR spectrum, 7, 657 synthesis, 7, 657 Azodn-5-one, 1-p-tolyl-IR spectrum, 7, 657 Azocinones... 

H,12H-Dibenz[c,/]azocine, 5,6-dihydro-N-methyl-conformation, 7, 706 Dibenzazocinones synthesis, 7, 665 Dibenz[6,/]benzazecines synthesis, 7, 528 Dibenzobarrellene oxide heating... 

In contrast to most other azacyclooctatetraenes, for azocine a synthesis of the parent system 1 is known. Substituted derivatives are much more stable and, therefore, have been preferentially investigated. 2-Alkoxyazocine systems have attracted particular interest due to the fact that they are available by an easy synthesis and are rather stable compounds.6... 

The known, in many cases very special, synthetic approaches to azocines often proceed via valence isomerization of appropriate precursor molecules. In this section these routes are classified by the last step in the reaction cascade. The synthesis and chemistry of azocines has been described in several excellent reviews,9-11 so that the treatment here is systematic and rather concise. 

The first and to date only synthesis of the parent system 2 uses a flash-vacuum pyrolysis (FVP) of 7,8-diazapentacyclo[4.2.2.02-5.03 9.04 10]dec-7-ene (diazabasketene, 1). After condensation at -196 °C, the pyrolysis product is distilled in vacuum to give pure azocine in ca. 60% yield.12... 

Semi bull valcncs are well-known intermediates in the synthesis of cyclooctatetraenes, 1,5-diazo-cines and 1,3,5,7-tetrazocines. There are also some examples for the synthesis of azocines, although so far only for W-substituted lactam derivatives, e.g. 1.25,26... 

Tandem Enlargement of the Six-Membered Ring in Heteroannulated Tetrahydropyridines under the Action of Activated Alkynes - A General Method for the Synthesis of Condensed Azocines 116... 

The chemistry of heteroannulated azocines has not been explored in detail owing to the lack of efficient methods for their synthesis. The exception is azocinoindoles, which have been investigated extensively due to the host of alkaloids with an azocinoindole fragment in their structure. 

Only two examples of the synthesis pyrimidoazocines have been described. In Ref. 82JHC1257, a three-stage synthesis of a new heterocycle system, pyrimido[5,4-c]benz[l]azocine, has been proposed. Condensation of 4-methyl-2-phenyl-5-pyrimidincarboxylate (112) with 3,4-dimethoxy-6-nitrobenzaldehyde (113) led to the substituted alkene 114, which, after catalytic hydrogenation of the nitro group on Raney nickel and subsequent intramolecular cyclization of product 115, was converted into pyrimidobenz[l]azocine 116 (Scheme 32). 

In recent years much attention has been paid to the synthesis of benzomorphane heteroanalogs in which a benzene ring has been replaced by a heteroaromatic one. Syntheses of substituted thieno[3,2-/]morphanes (derivatives of thieno[2,3-d]-azocine) described in Ref. 75JHC651 consists of the condensation of cyanopyri-dines 120 with 2-thienyllithium, reduction of the resulting ketones into thienylmethylpyridines, quaternization and reduction of the quaternary salts with sodium borohydride to form piperidines 124 and 125. Intramolecular cyclization of the latter leads to the formation of thieno[2,3-d]azocines 126 (Scheme 34). 

---