3/7-Azepine conformations

Schmidt reaction of ketones, 7, 530 from thienylnitrenes, 4, 820 tautomers, 7, 492 thermal reactions, 7, 503 transition metal complexes reactivity, 7, 28 tungsten complexes, 7, 523 UV spectra, 7, 501 X-ray analysis, 7, 494 1 H-Azepines conformation, 7, 492 cycloaddition reactions, 7, 520, 522 dimerization, 7, 508 H NMR, 7, 495 isomerization, 7, 519 metal complexes, 7, 512 photoaddition reactions with oxygen, 7, 523 protonation, 7, 509 ring contractions, 7, 506 sigmatropic rearrangements, 7, 506 stability, 7, 492 N-substituted mass spectra, 7, 501 rearrangements, 7, 504 synthesis, 7, 536-537... 

However, the relative stabilities of azepine conformers are highly dependent on the nature of the ring substituents, and some substantial inversion energy barriers have been noted, e.g. dimethyl 2,7-dimethyl-3//-azepine-4,6-dicarboxylate [57.3 kJ - mol-coalescence temperature (Tc) 25 5°C],76 isochalciporone (26)(49.4kJ mol-1 Tc 2 + 1 C),40 and 2,4,6,7-tetraphenyl-3/7-azepine (68.1 kJ mol-1 Tt 80°C).37 Ring-inversion activation energies of similar magnitudes have been determined for 4//-azepines.83 85... 

Dibenz[6, e]azepines conformation, 7, 499 11 H-Dibenz[f>, ejazepines oxidation, 7, 525 reduction, 7, 517 synthesis, 7, 532, 533 Dibenz[6,/ azepines JV-acyl derivatives UV spectra conformation, 7, 499 mass spectrum, 7, 501 nitroxide... 

IH-Azepine, 1-methoxy carbonyl-cycloaddition reactions, 7, 522 with nitrosobenzene, 7, 520 tricarbonyliron complex acylation, 7, 512-513 conformation, 7, 494 tricarbonylruthenium complex cycloaddition reactions, 7, 520 1 H-Azepine, l-methoxycarbonyl-6,7-dihydro-synthesis, 7, 507... 

H -Azepin-2-one, 4-allyloxytetrahydro-Claisen rearrangement, 7, 508 1 H-Azepin-2-one, hexahydro-conformation analysis, 7, 499 mass spectra, 7, 501... 

The [4-1-3] cycloaddition has also been realized in acceptors containing a nitrogen atom. While a,/ -unsaturated aldimines, and structurally flexible ketimine such as (87), generally only undergo [3-1-2] cycloadditions (see Scheme 24), the ketimine (112), which is rigidly held in a cisoid conformation, does give exclusively the [4-1-3] adduct azepine (113). On the other hand, the steroidal imine (114) produces a quantitative yield of a 1 1 mixture of the [4-1-3] and [3-1-2] cycloadducts (115) and (116), respectively (Scheme 2.31) [36]. 

The conformation of the 1ff-azepine ring has stimulated much interest since a planar lff-azepine would possess a destabilizing antiaromatic 8jc-electron system.14,15 In fact, early... 

X-ray crystallographic analyses of various 3//-azepines indicate that, like the 1//-azepines, they have a boat conformation.28,36 38,289 In both isolable tautomers of the highly substituted 3//-azepine 11, the hydrogen at the sp3 carbon occupies an equatorial position with the carbon inclined at an angle of 57c to the planar hull. 28 3-[Hydroxy(diphenyl)methyl]-3//-azepine has a similar boat conformation, but with the 3-substituent in the equatorial position.39... 

Compilations of UV data for 1-acyl- and 1-sulfonyl-l//-azepines are available.61 These systems display three major absorptions at 210-215, 240-247 and 285-330 nm. The weak, long wavelength band, which is thought to be due to interaction of the nitrogen lone pair with the triene system, often extends into the visible region and is responsible for the orange-yellow color of many 1-substituted 1//-azepines. 2,7-Disubstituted 1/7-azepines, in which the azepine ring is in the boat conformation, are colorless.61... 

IR data are of no importance for the characterization and structural elucidation of azepines. NMR Spectra and Conformational Studies... 

Ring inversions of 1H- and 4//-azepines between their two stable boat forms have been studied extensively by HNMR spectroscopy.37,38-40-76 82,85 A coalescence temperature of — 55 7 C and a AG value for ring inversion of 42.7 kJ mol have been determined for the two conformers 10 A and 10 B of A-phenyl-3//-azepin-2-amine.82... 

The photolysis of 2 -azido-2,4,4, 6-tetramethylbiphenyl (47) in diethylamine gives 10% of a mixture of A,iY-dicthyl-4-methyl-7-mesityl-3//-azcpin-2-amine (48) and the isomeric 3H-azepine 49, together with the unexpected 4//-azepine SO as the major product." Formation of the 4//-azepine is attributed to severe steric interactions in all conformers of the 3H-tautomers. 

An X-ray crystal structure of 7-methoxy-5//-dibenz[c,c]azepine reveals that the seven-mem-bered ring is in the boat conformation.7 Likewise, X-ray structural determinations of 2-morpho-lino-5H-d benz.[A/]azepi ne,7 and 5//-dibenz[/>, /]azepi ne.1 " 11 and its 5-acyl derivatives,12 in-... 

The photoelectron spectra of 11 //-dibenz[Z>,e]azepine52 and 5//-dibenz[6,/]azepine53 have been measured. The results for the latter suggest that in the gas phase, the molecule has an almost planar conformation. A comparison of the photoelectron spectra of 5-methyl- and 5-acetyl-5 H-dibenz(7 ,/]azepine supports the important contribution of the amide mesomer to the latter.32... 

Molecular orbital based molecular mechanical (MOMM) calculations have been carried out on 3H-2-benzazepinyl phosphonates.43 Similar calculations on 5//-dibenz[Z>,/]azepine lead to the prediction that there are two stable boat conformations for the seven-membered ring both of which are more stable than the planar form by 22.6 and 10.9 kJ moP, respectively the more stable conformer being the one in which the proton on nitrogen is exo lo the azepine... 

Scheme 32 Synthesis of piperazine incorporating fused azepine-tetrazoles 183 and two representative 3D conformations of 183A blue) and 183B cyan)...

Semiempirical and molecular mechanics calculations have been widely used. Thus, conformation of indolo benzazepine 423 (Figure 8) with its conjugated benzo and indole rings has been studied by molecular mechanics (MMX force field). Its planarity was estimated from a calculation of dihedral angle Ti 2 3 4 the value of ca. 22° is due to strain as contributed by azepine ring. This characteristic was further compared to that of the open-chain and six-membered... 

Q Which of the following heterocycles conform to the Huckel rule (4h +2) for aromaticity (i) furan (ii) l//-azepine (iii) pyrylium perchlorate [chlorate(VIl)] ... 

Medium-sized and large ring systems often show complicated conformational interconversions involving pseudorotations in one or even more conformational families. This makes stereochemical assignments in diastereomers rather difficult. Thus, very few systematic studies have been published. The situation is improved if such rings are embedded in polycyclic systems, or if they contain double bonds, which leads to restricted conformational mobility. An example is the differentiation of diastereomeric 2,3-dihydro-lf/-benzo[6]azepines 1 on the basis of y-gauche effects and on d(13C) and 3/H H values640. 

Historically, H NMR spectroscopy was vital in determining the structure of the first azepines (66T81) and has since proved to be invaluable in the conformational analysis of azepines and their benzologues, and in determining ring inversion activation energies of these conformationally mobile ring systems. 

A coalescence temperature of -55 7 °C was observed for the two conformers (17 18 R = H, X = NHPh) and AGf for the ring inversion was calculated to be 42.7 kJ mol-1. This figure is some 7.1kJmoF1 higher than for 3//-azepin-2-one (67CB335). The relative stabilities of the two boat conformations depend very much on the nature of the substituents and some substantial energy barriers to inversion have been determined. For example, AG for the 3//-azepine (20) is found to be 57.3 kJ mol-1 (71JOC978). 

Conformational analysis of hexahydro-lH-azepin-2-one (caprolactam) confirms that it, like other five- to eight-membered lactams, has the cis conformation. The 1SN NMR shift for the seven-membered lactam in CHCI3 appears at 259.7 p.p.m. (upfield from HNO3) (76JA5082). Solvent shifts for the 1SN resonance of caprolactam have been determined (78MI51601). In TFA/(15N-H) is 92.5 0.5 Hz. 

A study on the conjugate acids of dihydro-6//-dibenz[c,e]azepines has demonstrated the validity of the Karplus equation for determining H—N—C—H coupling constants in secondary and tertiary amines of known rigid conformation (73CJC2433). 

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