Seven-membered ring heterocycles with

Oxepin 1, thiepin 2 and azepine 3 are the parent compounds of the seven-membered heterocycles with one heteroatom. Of the seven-membered ring heterocycles with several heteroatoms, only diazepines e.g. 1,2- and 1,4-diazepines 4 and 5 will be discussed. 

It was not possible to obtain seven-membered ring heterocycles with a longer chain, and the cationic complex was unstable. The limit to the formation of the 7r-cation intermediate is related to the steric hindrance of the substituents on the 7-carbon (Scheme 35). ... 

The only heterocyclic seven-membered ring system with maximum unsaturation containing six heteroatoms is 1,3A4,5,2,4,6-trithiatriazepine (1). The methoxycarbonyl derivative 2 is a minor product (14%) of the complex reaction of tetrasulfur tetranitride with dimethyl acetylenedicarboxylatc in refluxing toluene, which gives mainly dimethyl l,2,5-thiadiazole-3,4-dicarboxylate (3, 67%) (see Houben-Wcyl, Vol. E8d, pl54ff which includes an experimental procedure). Two other products are the trithiadiazepine 4 (5%, see Section 4.4.1.1.1.) and the 1,2,4-thiadiazole derivative 5 (3%).385... 

From Other Seven-Membered-Ring Compounds with Fused Heterocyclic... 

The Mannich reaction consists on the condensation of a CH-activated compound with a primary or a secondary amine and a non-enolizable aldehyde or ketone to afford p-aminocarbonyl derivatives known as Mannich bases (Scheme 20). This sequence is of great use for the constmction of heterocyclic targets, as illustrated for example by the Robinson-Schopf synthesis of tropinone in 1937 or by the preparation of some azabicyclo[3.3.1]nonanones or pyranocoumarine derivatives (Fig. 1) [100]. In the following, representative recent examples of the formation of five- to seven-membered ring heterocycles will be presented. 

There are now two possible routes to the final product. Reductive elimination would insert the new alkyne into one of the old C-Co bonds and form a seven-membered ring heterocycle. This could close in an electrocyclic reaction to give the new six-membered ring with the cobalt fused on one side and hence the cobalt complex of the new benzene. 

Likewise, reaction of the seven membered ring heterocyclic iminophosphoranes 9 with phenyl isocyanate gives the corresponding carbodiimides 10. ... 

In more modern times, the first successful anti-ulcer drug, cimetidine 3, with its ability to block histamine synthesis in the stomach, is an imidazole and the classical anti-depressant valium 4 has a seven-membered ring heterocycle that is not (quite) aromatic. 

The NMR spectra of heterocyclic compounds with seven or more ring members are as diverse as the shape, size and degree of unsaturation of the compounds. NMR is perhaps the most important physical method to ascertain the structure, especially the conformational statics and dynamics, of large heterocycles. Proton-proton coupling constants provide a wealth of data on the shape of the molecules, while chemical shift data, heteroatom-proton coupling constants and heteronuclear spectra give information of the electronic structure. Details are found in Chapters 5.16-5.22. Some data on seven-membered rings are included in Table 10. 

Preparation of spirooxaziridines from cyclic ketones poses no problems nor does oxaziridine synthesis from cyclic Schiff bases, which was preferably carried out with pyrro-lines to give, for example (245) (59JCS2102) and, in connection with tranquilizer synthesis, with heterocyclic seven-membered rings to give, for example, (246) (63JOC2459). 

In an earlier study the authors proposed a [3.2.0] bicyclic sulfonium salt 8 as the reactive intermediate in the trimethylsilyl iodide mediated ring contraction of 4-methoxythiephane <1996T5989>. Enantiomerically pure thio-lane derivatives were synthesized via a ring contraction of a seven-membered sulfur heterocycle by nucleophilic transannular substitution <2000TA1389>. The thiepane derivative 15, derived from d-sorbitol, was converted into the dimesyl derivative 16 following deprotection under acidic conditions. Treatment of 16 with sodium azide in DMSO at 120°C yielded the corresponding thiolane as a mixture of two diastereoisomers, 17a and 17b, in a 5 1 ratio (see Scheme 1). 

Condensed 1,2,4-Triazines II. Fused to Heterocycles with Six- and Seven-Membered Rings and Fused to Two Heterocyclic Rings... 

Several condensed 6-7 bicyclic systems have been prepared from AAs. Some Af -chloroacetylated AAs are photochemically transformed into heterocycles with a condensed seven-membered ring. For example, A-chloro-acetyl-D,L-w-tyrosine is easily cyclized into benzazepinone 109a on irradiation with a high-pressure mercury lamp (67JA1039 68JA776). 

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