Azocine, structure

By far the most thoroughly investigated azocines are the 2-methoxy derivatives prepared and studied by Paquette and coworkers (7lAG(E)ll). The synthesis involves addition of chlorosulfonyl isocyanate to a cyclohexadiene, conversion to the imidate and introduction of another double bond by allylic bromination and dehydrohalogenation. Valence isomerization then ensues and 2-methoxyazocine (98) or alkyl homologs are isolated from this sequence in multigram quantities as stable yellow oils. NMR data (see 98) clearly indicate the monocyclic azocine structure the spectra are invariant from -70 to 180 °C and indicate less than 2% of the bicyclic valence isomers. 

Attachment of a polymethylene chain at the bridgehead positions markedly destabilizes the azocine structure, and the 3- and 4-atom bridged compounds exist entirely in the azapropellane form (99). With n = 5 the NMR spectrum is temperature dependent and... 

The corresponding ethano and propano compounds only exist in their propellane forms. Apparently, the smaller bridge leads to higher strain in the azocine tautomer, so that the triene structure predominates. Longer chains (> hexano), however, exhibit the normal behavior of tetraenic compounds. 

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. 

Problem 20.43 Write structures for (a) oxirane, (b) 1,2-oxazole, (c) 1,4-diazine (pyrazine), (d) l-thia-4-oxa-6-azocine, (e) 3H-1,2,4-triazole, (/) azepane. 

Some azocine derivatives showed insecticidal activity as assayed by oral administration to silkworms larvae <2000BBB1519>. The azocine ring was shown to be indispensable to form the active conformation. Benzazocine with the lactam structure was evaluated in the syntheses of homochiral polyamide polymers <1998TA3497>. 

Azocine formation by photocycloaddition of acrylonitrile to arenas is also observed when cyanobenzenes and cyanonaphthalenes are irradiated with ultra-violet light in the presence of phenols. The products have the structure (70) and are presumed to be formed by thermal ring opening of the primary ortho adducts (71). 

Figure 1. On the left, FR901483 structure with the replacement nomenclature numbering used in this review. On the right, FR901483 structure showing the heterocyclic system numbering (octahydro-1 //-7,1 Oa-inethanopyrrolo[ 1,2o]azocine) used by several authors.

This chapter details the nomenclature, thermodynamics, reactions, and synthesis, and summarizes the experimental structural methods and applications in the following order (i) unsaturated, partially saturated, fully saturated monocyclic azocines, (ii) benzazocines, and (iii) dibenzazocines. The nitrogen bridged systems and unique compounds are not given detailed treatment owing to space limitations. 

X-ray diffraction data confirmed the structure of the (5>. The relative configuration, in similar such systems, was determined by H and C NMR <89AP(322)21>. 

The reaction of acetyl-substituted aminopyran (101) with arylidenemalonitrile (102) afforded a novel bridge-head azocine (103) (Equation (14)). The controversy over its structure was resolved by x-ray crystallography <92T1581>. A one-pot, decarboxylative three-carbon ring expansion of a cyclic secondary amino acid afforded a tetrahydroazocine derivative <87CC1296>. 

X and Y, Electron withdrawing 7r-substituents (e.g. CN) appear to be essential for the stabilization of the norcaradiene valence isomer. Valence isomerization in the azocine series is also structure dependent. Thus (24) is wholly converted into (25) in the cases fi = 3 or 4, whereas with = 5 the equilibrium is only established at 100°, and when n = 6 only (24) is present. 

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