Azepines derivatives

H-Azepine derivatives form a diene complex with tricarbonyliron, leaving uncomplexed the third of the double bonds. If the 3-position is substituted, two different such complexes are possible, and are in equilibrium, as seen in the NMR spectrum. An ester group in the 1-position of the complex can be removed by hydrolysis, to give an NH compound which, in contrast to the free 1/f-azepine, is stable. The 1-position can then be derivatized in the manner usual for amines (Scheme 22). The same tricarbonyliron complex can, by virtue of the uncomplexed 2,3-double bond, serve as the dienophile with 1,2,4,5-tetrazines. The uncomplexed N-ethoxycarbonylazepine also adds the tetrazine, but to the 5,6-double... 

Formation of azepine derivatives by aza-[3,3]-Claisen rearrangements was first reported by Stogryn and Brois, an isomeric mixture of 2,3-divinylaziridines 166, generated by treatment of sulfonate 165 with NaOH, being converted into azepine 167 by steam distillation (Scheme 2.41) [61]. In this case, unchanged trans-azir-... 

Tungsten alkynyl Fischer carbene complexes are excellent dienophile partners in the classical Diels-Alder reaction with 1-azadienes (see Sect. 2.9.2.1). On the contrary, the chromium-derived complexes exhibit a different behaviour and they react through a [4S+3C] heterocyclisation reaction to furnish azepine derivatives [116] (Scheme 68). The reaction is initiated by a 1,2-addition of the nitrogen lone pair to the carbene carbon followed by a [l,2]-Cr(CO)5 shift-pro-... 

Indolones and isoindolones have been utilised in the synthesis of fused azepine derivatives. In the one reaction, rearrangement of the alkynes 18 to 2-benzazepine-l,5-diones 19 in the presence of Lewis acids has been reported <96XL393>. Xhe yields vary from moderate to very good. Xricyclic azepines 20 are obtained by the reaction of the 4-[2 -(p-toluenesulfonyloxy)ethyl]-2-oxindole with imines <96JHC209>. 

The use of metal complexed heterocyclic polyenes in these cycloadditions has also proven useful, as both the 1,1-dioxythiepine and azepine derivatives 250 and 253 took part in [6 + 4]- and [6+ 2]-photocycloadditions, respectively, to afford good yields of the... 

Classical methodology was used to prepare the dibenz[b,f]azepine derivative 21 (R = substituted pyrido[2,3-d]pyrimidine) utilising amide ion formation from dibenz[b,f]azepine itself with sodium hydride and then iV-alkylation with 2,4-diamino-6-bromomethylpyrido[2,3-d]pyrimidine. The bulky bis-fused azepine moiety was required to introduce steric bulk in the system and to study the effect of this on inhibition of the enzyme dihydrofolate reductase <00JHC921>. 

Similarly, according to Scheme 2.211 d, the INAC reaction of TV -ally 1-carbohydrate nitrone (472) gave the pyrrolo 1,2-a azepine derivative (473) (Scheme 2.228) (723). 

A majority of routes leading to bicyclic pyridoazepines schematically falls into four categories (Scheme 3) They can be described as 1.2 or 2.1 cyclizations, each of them basing on a pyridine (7a and b, respectively) or an azepine derivative (7c and d, respectively). Among the synthetic methods involved are classical ones (N-alkylation, lactamization, Dieckmann condensation, etc.) and an increasing part of enamine, enamide, and... 

Six-membered ring-closing metathesis is based on azepine derivatives bearing terminal alkenyl groups at both N-1 and C-2 positions. Such reactions form (isomeric to 94 and 98, respectively) lactams 114 (01JOM9056) and 115 (99SL1127). 

Table 5. H-NMR chemical shifts of bicyclic pyrido[l,2-fl]azepine derivatives... 

A free radical cyclization of oxime ethers tethered to an aldehyde has been used in the synthesis of azepine derivatives . For example, oxime ether 389 is cyclized to azepine 390 by reaction with Sml2 in HMPA and f-BuOH at —78°C (equation 170) . Similar free radical cyclization of oxime ethers can be carried out also in the presence of Bu3SnH/AIBN in benzene . Oxime 0-methyl ether 391 underwent thermal cyclization in refluxing o-dichlorobenzene (ODCB) leading to the mixture of two products 392 and 393 in ratio 69 31 in overall yield of 91% (equation 171) °. Rearrangement of oxime 0-tosylates in the presence of piperidine also leads to azepine ring formation . ... 

Winterfeldt and Nelke have shown that oxindole reacts with DMAD in presence of sodium hydride to give dimethyl oxindolylidine-3-succinate (204). However, when the reaction is carried out in the absence of any base, at around 200°, the products formed are the azepine derivative 205, the carbazole 206, and the furan 207 (Scheme 32). Similarly, the reaction of iV-methyloxindole with DMAD in presence of sodium methoxide gives rise to AT-methyloxindolylidine-3-succinate. ... 

Unexpectedly, the reaction of 284 toward tetracyanoethylene at room temperature resulted neither in the formation of the [4 + 2] adduct 299 nor in the formation of its azepine derivative, but the novel 4,6-diazasemi-bullvalene structure 300 was isolated as colorless crystals in 70-85% yield (90CC1057) (Scheme 66). Although mechanistic rationalization of this process is not a simple matter, a possible reaction course would involve the formation of Michael adduct 301, which would undergo intramolecular... 

Caprolactam or (hexahydroazepin-2-one) is, without doubt, the most important azepine derivative. This seven-membered lactam is produced in vast quantities as an intermediate for the manufacture of nylon 6 (B-75MI51601, B-70MI51601). Polymerization, which is carried out at high temperatures with water as the initiator or at low temperatures with a strong base (e.g. NaH), proceeds by attack at the caprolactam carbonyl by the amino function of the open-chain monomer, e -aminohexanoic acid. 

Dantanarayana, A. (Alcon Laboratories, Inc.) Phtalimide-piperidine, -pyrrolidine and -azepine derivatives, their preparation and their use as muscarinic receptor (ant)agonists, W09932479 (1999). 

This method has been utilized to construct other fused azepine derivatives, e.g., 85 from indolylallenes 83 (Scheme 26). Indirect evidence for the involvement of the azomethine ylides 84 came from their trapping in a [3 + 2] cycloaddition (97JOC7744). 

Fluorinated triazolines (Scheme 29) are particularly stable and require high temperatures for thermolysis when aziridines are obtained.145 Thermolysis of aryl-substituted triazolines is not well investigated144,175 the l-p-nitrophenyl-5-phenyl compound yields exclusively aziridine, whereas the 1,4-isomer gives the imine as the major product.175 1-Heterocyclic-substituted 5-vinyltri-azolines (Scheme 31) give S-vinylaziridines, which undergo thermal isomerization to azepine derivatives (e.g., 89).183... 

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