Azepine structure

X-ray studies on a number of azepines (Section 5.16.2.2) preclude the existence of the bicyclic tautomer in the crystal state, and for simple azepines variable temperature NMR evidence (-90 to 130 °C) is overwhelmingly in favour of the azepine structure. For example,... 

The preparation of perfluoroazepines is more facile. Hexafluoro-l//-azepine-l-carbonitrile (6a) is prepared by the reaction of hexafluorobenzene with cyanonitrcne.15 Likewise, the 1-ethoxycarbonyl derivative 6 b is prepared in moderate yield by the reaction of hexafluorobenzene with ethoxycarbonylnitrene.16 In each case, a benzoazirine intermediate is presumably involved, which isomerizes to the azepine structure. Perfluoroazepines 6 isomerize photolytically to the corresponding 2-azabicyclo[3.2.0]hepta-3,6-dicncs 7 in high yield.17 Azepine 6c is obtained from 6a by acid hydrolysis.17... 

The pyrimido[l,6-a]azepine structure 482 was attributed to both products, but the structure of the product obtained from 2,4,6-trimethylpyrimidine was later corrected to the tricyclic derivative 483 (77JCS(P1)1924). 

Initially it was believed that the 1,4-benzodi-azepine structure was an essential requirement for high affinity binding to the BZR, but a wide range of non-benzodiazepine chemo-types have since been shovm to bind to the BZR with high potency, rendering the term "benzodiazepine receptor" no longer strictly... 

Electrocyclic ring opening of the cyclobutene ring in the adduct 416 occurs upon FVP at 500 °C to give the bridged azepine structure 417 (Scheme 86 2000CEJ3706). 

H-Azepine, 2-allyloxytetrahydro-Claisen rearrangement, 7, 508 3H-Azepine, 2-amino-acylation, 7, 511 effect of acidification, 7, 510 nucleophilic displacement reactions, 7, 514 synthesis, 7, 533, 535 3H-Azepine, 2-amino-7-bromo-synthesis, 7, 529 3H-Azepine, 2-anilino-ring inversion, 7, 495-499 structure, 7, 533... 

Dibenz[h,e]azepine-6,11-diones ent-Morphinan nomenclature, 1, 29 Morphinan, 1,2,3,4-tetrahydro-nomenclature, 1, 29 14-a-Morphinan, N-methyl-synthesis, 1, 480 Morphinans nomenclature, 1, 29 as pharmaceuticals, 1, 148 synthesis, 2, 377 Morphine, 2, 512 as analgesic, 1, 167 as metabolite of normorphine, 1, 235 as pharmaceutical, 1, 146, 147, 148 synthesis, 1, 480 Morphine alkaloids structure, 4, 534 Morphin-7-en nomenclature, 1, 29 Morphinone, dihydro-as pharmaceutical, 1, 147 Morpholine — see also 1,4-Oxazine, tetrahydrocarcinogenicity, 1, 229 corrosion inhibitor, 1, 409 metabolism, 1, 226 nomenclature, 3, 996 structure, 2, 5 synthesis, 2, 89 Morpholine, 4-aciyloyl-polymers, 1, 291 Morpholine, alkenyl-polymers, 1, 291... 

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]. 

Therapeutic Function Analgesic, Anticonvulsant Chemical Name 5H-dibenz[b,f] azepine-5-carboxamide Common Name 5-carbamyl iminostilbene Structural Formula ... 

Chemical Name 1,2,3,4,10,14b-hexahydro-2-methyldibenzo[c] pyrazino[1,2-a] azepine Common Name 2-methyl-1,2,3,4,10,14b-hexahydro-2H-pyrazino-[1,2-f] morphanthridine Structural Formula ... 

Chemical Name 6-(4-methyl-1-piperazinyl)-11 H-dibenz[b,e]azepine Common Name 6-(4-methyl-1-piperazinyl)morphanthridine Structural Formula ... 

The cyclopentazepine systems are often1-5 referred to as 4-aza-, 5-aza-, and 6-azaazulene, respectively. Confusingly, the cyclopent[a]azepine 8a, which is more correctly known as 1ff-pyrrolo[l,2-a]azepine, has been referred to as 4-azaazulene6 and as 3a-azaazulene.7 Only the carbonyl derivative 8b of this nonconjugated system is included in this section since it can be represented as the fully conjugated, aromatic, dipolar structure 9.6... 

Dimethyl 2,7-dimethyl-4//-azepine-3,6-dicarboxylate, which was the first 4//-azepine to be isolated and characterized,29 on heating, or on treatment with sodium ethoxide in ethanol, rearranges quantitatively to the 3//-isomer. The X-ray crystal structure of dimethyl 7-(dimethylamino)-6-methyl-4//-azepine-2,3-dicarboxylate has been determined.42... 

Although theseazepin-2-onesexhibitdeshieldedprotonresonances(<5 = 7.8 8.2), with an ortho coupling for the 5,6-unsubstituted derivative of J5 6 = 10 Hz, an X-ray structural analysis of ethyl 7-(4-bromophenyl)-3-methoxy-2-oxo-6-phenyl-27/-azepine-4-carboxylate reveals a non-planar azepine ring 48 53 3,5-Dihaloazepin-4-ones have been detected recently in the photolysis of 4-azido-2,6-dihalophenols at 12-14 K.286... 

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

Apparently, the 1H NMR spectra of 1 //-azepines are invariant over substantial temperature ranges.61 However, temperature dependence has been noted69 in the 13CNMR spectra of some 1 -acyl-1 //-azepines, and is attributed to hindered rotation about the N-CO bond rather than to ring-inversion phenomena AG free enthalpies of activation for hindered rotation of 62-66 kJ moP1 have been calculated. E/Z-rotamcr ratios for l-aroyl-l//-azepines have been assessed and show a slight preference for the -rotamer 22 however, an X-ray structural analysis of l-(4-bromobenzoyl)-2-methyl-3.5,7-triphenyl-l//-azepine demonstrates that in the crystal state it is exclusively in the E configuration.22... 

A comparison of the electron impact (El) and chemical ionization (Cl-methane) mass spectra of 1//-azepine-1-carboxylates and l-(arylsulfonyl)-l//-azepines reveals that in the El spectra at low temperature the azepines retain their 8 -electron ring structure prior to fragmentation, whereas the Cl spectra are complicated by high temperature thermal decompositions.90 It has been concluded that Cl mass spectrometry is not an efficient technique for studying azepines, and that there is no apparent correlation between the thermal and photo-induced rearrangements of 1//-azepines and their mass spectral behavior. 

Treatment of the Z-aldehyde 9 (R1 = R2 = H) with trifluoroacetic acid in dichloromethane at — 10 C, then with l,4-diazabicyclo[2.2.2]octane or /V,/V-diethylpyridin-4-amine, constitutes the first synthesis of 27/-azepine (10, R1 = R2 = H) which was isolated, with great difficulty and in very low yield (1 %), as a highly volatile, unstable oil, the structure of which was confirmed by high field H and 13CNMR spectroscopy.290 Similar treatment of the Z-alkenones 9a-d furnishes the thermally unstable (5)-2/7-azepines lOa-d in much higher yields.291... 

The dimethyl 4//-azepine-2,3-dicarboxylate 17 is obtained in high yield by the action of dimethyl acetylenedicarboxylate on jV,Ar,2-trimethyl-2-vinyl-2//-azirin-3-arninc (16).42 The structure of this surprising product has been confirmed by X-ray analysis. 

Ring expansion of the benzene ring of a calix[6]arene to a 1 //-azepine in 14% yield by photolysis of an aryl azide confined in the calix structure has been reported.294... 

The structure of the tar, formed in many azide decompositions, consists of polyazepine units,103 and arises by attack of arylamine, formed from triplet arylnitrene, on the azepine precursor 30 to give the l//-azcpin-2-amine 31, which acts as a nucleophile towards more azepine precursor to yield ultimately the polyazepine 95. 

In an elegant series of reactions, it has been demonstrated that 1//-azepines can be forced into adopting the benzene imine structure 8 by bridging the 2- and 7-positions with a trimethyl-ene chain.61 The length of the alkyl chain, however, is critical and the tetramethylene derivative exists solely as the 2,7-bridged l//-azepine (see Section 3.1.1.4.1.3.). 

The cycloadducts formed from ethenetetracarbonitrile and the three isomerically pure methyl methyl-1//-azepine-l-carboxylates, 4, 5 and 6, have been subjected to a rigorous structural examination, from which it was concluded that adducts bearing the methyl groups at the bridgehead positions are not formed.251 Thus, the 2-methyl and the 4-methyl isomers, 4 and 5, each yield only one adduct, 7a and 7b, respectively, whereas methyl 3-methyl-1//-azepine-l-car-boxyate (6) gives 66 % yield of a 45 55 mixture of the 4-methyl 7 c and 7-methyl 7 d cycloadducts. 

An X-ray structural analysis has confirmed that ethyl 1//-azepine-1-carboxylate (1) and nitrosobenzene yield the [6 + 2] adduct 1 1 183-254 255 Subsequently, however, a careful analysis of the reaction mixture by HNMR spectroscopy indicated that a [4 1 2] adduct is also formed, albeit in low yield, to which structure 12 was assigned.256... 

Structure 12 may need to be revised, however, since a recent X-ray crystallographic analysis on the corresponding [4 + 2] cycloadduct 13 from ethyl 1//-azepine-1-carboxylate (1) with ethyl 4-nitrosobenzoate reveals the opposite regiochemistry to that proposed for the adduct with nitrosobenzene.297 The [6 + 2] adduct is also formed, in this case in 41 % yield (mp 106-107 C). 

Cycloadditions to 2H- and 3//-azepines are much less common however, with the tetra-zinedicarboxylate 36, /V./V-diethyl-3/7-a/.epin-2-amine (38) yields the bisadduct 39 whose structure has been confirmed by X-ray analysis.266 267... 

Similar problems arise with the four isomeric dibenzazepines 4-7. since only 5//-dibenz-[6,d]azepine (4) and 5//-dibenz[/>,./]azepine (7) can be drawn as fully benzenoid ring structures. Even so, 5//-dibenz[/ ,t/]azepines are rare and are known only as the 7-oxo derivatives.4 In contrast, 5//-dibenz[6,e azepine (5) and 6//-dibenz[r,t>]azepine (6) exist only as the 11//- 5a and 5H- 6a isomers, respectively. In fact, there is no chemical or spectrosopic evidence for the isomerization of 5//-dibenz[e,e]azepine,5 or its 6-oxide,6 to the 6//-dibenz[r, e]azcpinc isomer (6). In addition, an X-ray crystal structure of 7-methoxy-5//-dibenz[e,e]azepine supports unequivocally the benzenoid rather than the quinonoid form.7 9//-Tribenz[6,d /]azepine (8) has only recently been prepared.8... 

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-... 

Surprisingly, X-ray structural analysis of the dark-green, hygroscopic tetrabutylam-monium salt of 5//-dibenz[6,/]azepine reveals that the potentially antiaromatic 5//-dibenz-azepine anion has a less pronounced nonplanar butterfly structure (161° vs. 144 ) than 5H-dibenz[6,/]azepine.243... 

Detailed IR and UV spectroscopic data on 5//-dibenzfc,c]azepine5 and its 7-methoxy- and 7-methylsulfanyl derivatives7 have been reported. IR, UV and HNMR spectroscopic data for 2-amino-3//-l-benzazepin-3-one, 2-amino-l//-3-benzazepin-l-one, and 6-amino-7H-dibenz[7>,(/]azepin-7-one have been gathered,27 and confirm their oxo amidinc structures. Spec-trophotometrically determined pATa values of 4.46 and 5.20 (in water at 21 C) have been obtained for 1 l//-dibenz[(>,e]azepine and its 6-methyl derivative, respectively.28... 

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