Diazepines tautomerism

A well-studied case of tautomerism is that of l,2-diazepin-4-ones tautomers 47a and 47b were characterized by NMR, the former being the most stable (85JOC2141). 3,5-Dihydro-4//-2,3-benzodiazepin-4-ones exist as 48a and not as 4-hydroxy tautomers 48b (74JHC401). 

Wentrup s paper [98JCS(P2)2247] contains one of the very few contributions to the tautomerism of functionalized 1,3-diazepines. l,3-Dihydro-l,3-diazepin-2-ones (49a) exist as such and not as hydroxy tautomers 49b ( H and NMR in DMSO solution and IR in the solid state). 

A careful and NMR study of 1,5-benzoxazine and 1,5-benzo-diazepine shows that these compounds exist in the amino-thione forms 55 and 56, respectively. Compound 55 displays a solvent-dependent amino/imino tautomerism (92MRC673).Tricyclic compounds 57, analogous to the bicyclics discussed above have been described they exist in the tautomeric form shown below (87BSB399,92BSB995,96BSB345). 

Under acidic conditions, dienone tosylhydrazones 5 cyclize to 1 -tosyl-6,7-dihydro-l//-l,2-diazepines 6,l04a which on treatment with sodium ethoxide eliminate the elements of/Moluenesul-finic acid to yield an equilibrium mixture of the tautomeric 3//-1,2-diazepines 7 and 8.104b... 

A mixture of ethyl 3,5-dimethyl-l/f-thieno[2,3-c]-1,2-diazepine-l-carboxylate (6) (10-15%) and the isomeric ethyl 2,5-dimethyl-3//-thieno[2,3-t/]-l, 3-diazepine-3-carboxylate (8) (50-60%) is obtained when a solution of the thienopyridine A-iminc 4 in benzene is irradiated with a 400-W high-pressure mercury lamp for 2-3 hours at 20rC. It has been suggested that product 6 is formed from the intermediate 5. The isomeric intermediate 7 undergoes two consecutive walk rearrangements, followed by valence tautomerization, to give the major product 8.168... 

Fully unsaturated monocyclic 1,4-diazepines have been reported only recently. Representatives of the three tautomeric systems 1H-, 2H-, and 6//-l,4-diazepines are known, but 5//-l,4-di-azepines have not been described. 

Throughout this article, the terms dihydrodiazepine and dihydro-diazepinium are used exclusively to refer to 2,3-dihydro-l,4-diazepines (1) and their monocations (2), respectively. Spectroscopic data show that the dihydrodiazepines normally exist in the conjugated form (1) rather than in the tautomeric bisimino form (3). 

Under thermal conditions bicyclic azetines undergo facile valence bond tautomerization. Typically, l-azabicyclo[2.2.0]hexadienes give pyridines (equation 16) (76CPB2219), 1,2-diazabicyclo[3.2.0]heptadiene (126) gives diazepine (127) (77CJC56) and 2-... 

Annular tautomerism between one or more NH-forms and various CH forms of 1,2-diazepines is possible with the favored species dependent upon the nature and position of substituents (69ACS3125, 70T739). Interestingly, unlike monocyclic azepines and tautomeric 1,2-diazepines, 5H- 1,2-diazepines (47) exist preferentially in their bicyclic diazanorcaradiene form (48) (72JA2770). 

Reaction of tosylhydrazide with a,(3,y,8-unsaturated ketones, followed by dehydrotoluenesulfonyla-tion affords 3//-1,2-diazepines (Scheme 25) (84JCS(Pl)158l). Tautomeric products (125) and (126) are... 

Iminopropadienones are highly reactive species that have been used as three-carbon fragments in the synthesis of 1,4-diazepines <2002JOC2619>. Aryl- and neopentyl-substituted iminopropadienone derivatives are stable at 25 °C and the latter, 99, reacted with iV,iV -dimethyl-l,2-diaminoethane to afford a 55% yield of the l,4-diazepin-5-one 100, a compound that partially tautomerized to the enamide 101 upon Kugelrohr distillation. 

Fused diazepines like 54 and 56 can exist in several tautomeric forms (Scheme 4.16)—enamine 1H (A), enamine 5H (C) and diimine 3H (B) (Scheme 4.16). 

The problem of tautomeric equilibriums in annelated 1,5-diazepines was studied in [68] by means of NMR spectroscopy, X-ray analysis and quantum-chemical calculations. It was shown that the electron-withdrawing rings (e.g., pyrimidine moiety) fused with the diazepine cycle increase the stability of the antiaromatic enamine tautomeric forms A and C, while in the case of benzodiazepine, a diimine tautomer B was found to be the most stable. Ab initio quantum-chemical calculations and NMR spectroscopic data showed that solvation of seven-membered heterocycles with polar solvents contributes considerably to the stabilization of the enamine forms A and C. This assumption was also proven by X-ray analysis, which showed that in the solid state these diazepines exist in the diimine form B. 

Treatment of a solution of 2,4-dimethylbenzodiazepine in benzene with gaseous DC1 led to N-deuteriation but no C-deuteriation (63JA3354). There is an implication here that H/D exchange does not take place at C-3, as happens in 2,3-dihydro-l,4-diazepines, for traces of either the tautomeric... 

Treatment of 1 //-pyrrolo[2,3-7>]pyridine (1) with mesitylenesulfonylhydroxylamine resulted in Anamination of the pyridine nitrogen in high yields. Upon addition of a base such as potassium hydroxide the ylide which formed rapidly underwent tautomerization to give 7-ami no-7//-pyrrolo[2,3-A]pyridine in nearly quantitative yields. For some substituted derivatives, which did not undergo tautomerism, diazepines were formed upon irradiation. The diazepines were too unstable to be isolated <79CPB2183> (see Section 7.06.5.1.2). 

Stages involved in the reaction of 2,3-butanedione with propylenediamine have been monitored by NMR spectroscopy as well as by the isolation of products. The reduced 1,4-diazepine 194 was isolated, together with the macrocyclic dimeric product 196 and the tetrahydropyrimidine 195. NMR spectroscopic evidence was obtained for the first formed imine 193 and the tautomeric diazepine 197 [02H11]. 

The 1,3-diazepine 83 (R = CF3, Alk = CH3) has been shown to have the NH structure in the solid state <20040BC1227>. The average free energy of activation for interconversion of the tautomers 83 and 84 (R = H, Aik = Me, Et, Pr1) has been determined to be 16.2 kcal mol1 by the ForsenHoffman double resonance saturation transfer method <20040BC1227>. The most stable tautomeric forms of a variety of diazepine derivatives have been documented in CHEC-III(13) and earlier editions. 

Reaction of tosylhydrazide with -unsaturated ketones, followed by dehydrotoluenesulfonylation affords 3//-l,2-diazepines (Scheme 85) <1984J(P1)1581>. The tautomeric products 170 and 171 are in dynamic equilibrium at room temperature but can be separated by high-pressure liquid chromatography at 6C. 

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