Diazepine salts

Chlorocycloalk-l-ene-l-carbaldehydes react analogously with benzene-1,2-diamine to give benzo[6]cycloalka[e][l,4]diazepine salts 16.21 6... 

In the reactions of a,/I-unsaturated ketones with ethylene-diamine perchlorate 1,4-diazepine salts are by-products of tetra-azamacrocycle formation. But for... 

Triarylpyrylium salts react with hydrazine to give 4//-l,2-diazepines 472-1°s,ioo vja g unstable intermediates 3.110 The reaction fails with pyrylium salts containing alkyl groups in positions 2 and 6, with the exception of 2,4,6-tri-tert-butylpyrylium perchlorate. In some cases it is advantageous to use a thiapyrylium salt in place of the pyrylium salt. Selected examples are given. 

Electrocyclization of certain a,/ y,<5-unsaturated diazo compounds, in which one of the double bonds is embedded in an aromatic ring, affords benzodiazepines. The diazoalkenes 1, produced by heating the sodium salts of the corresponding tosylhydrazoncs, can undergo two kinds of cyclization, [1,5] to yield 3//-pyrazoles, and [1,7] to give diazepines. 

Cyclizations of doubly unsaturated diazo compounds containing a thiophene ring within rather than at the end of the diene system to yield thicnodiazepines have also been reported. Thus, thermolysis of the sodium salt 7 gives the l//-thieno[3,2-r/]-2,3-diazepine 9. The intermediate 8 rearranges to the more stable product 9 by a symmetry allowed [1,5] shift of hydrogen.14,1... 

A valence bond isomer of pentakis-(trifluoromethyl)-l, 3-diazepine (44) was prepared from (43) (81TL1113) (44) can be transformed thermally or photochemically to a 2,4-diazabicyclo(3.2.0)hepta-2,6 diene (45), which was subsequently photolysed to an imidazole in an anionic process. Compound (45) is highly acidic arising out of the bishomoaromaticity of the anion and forms a salt with Et3N (81TL1369). 

Chorazepate Chorazepate, 7-chloro-2,3-dihydro-2,2-dihydroxy-5-phenyl-1H-1,4-benzo-diazepin-3-carboxylic acid (5.1.34), which is used in the form of a dipotassium salt, is synthesized by yet another interesting synthetic scheme. 2-Amino-5-chlorobenzonitrile is used as the initial compound, which upon reaction with phenyhnagnesiumbromide is transformed into 2-amino-5-chlorbenzophenone imine (5.1.32). Reacting this with amino-malonic ester gives a heterocyclization product, 7-chloro-l,3-dihydro-3-carbethoxy-5-phenyl-2H-benzodiazepin-2-one (5.1.33), which upon hydrolysis using an alcoholic solution of potassium hydroxide forms a dipotassium salt (5.1.34), chlorazepate [30-32]. 

Perhaps the most consistently satisfying and enjoyable feature of the chemistry of 2,3-dihydro-1,4-diazepines and 2,3-dihydro-l,4-diazepinium salts has been their ability to provide, quite consistently, unexpected results and products. There is every hope that these compounds will continue to maintain this tradition and provide interesting new facets in their chemistry in the future. 

We thank Dr. D. R. Marshall (University College of North Wales) for constructive help in compiling this review and for his general contributions to our understanding of 2,3-dihydro-1,4-diazepines and their salts we have in places unashamedly plagiarized his words, and conversations over the years have contributed much to the review. We also thank Dr. S. Mesher for Chem Drawing the formulae. 

Various ot,p y,5-unsaturated 1,3-dipoles are known to undergo 1,7-cyclization by a 871-electrocyclization process (329,330), and the corresponding diazo compounds behave similarly. 5-Diazopenta-l,3-diene derivatives such as 285 (Scheme 8.70), generated in situ by thermolysis of the corresponding tosylhydrazone sodium salts, cyclize to form 1,2-diazepines (286) (331). Sharp and co-workers studied the mechanism, scope, and limitations of this transformation. It was found that cis-substitution about the y,8-double bond prevents the 1,7-cyclization and directs the system toward 1,5-cyclization (332,333) (i.e., formation of a 3//-pyrazole), and that the ot,(3-double bond can be part of a phenyl ring (334). In special cases, the y,8-double bond can be incorporated as part of an aromatic [287 288 (335)] or 2- or 3-thienyl ring as well (336). 

A related 1,7-cyclization has been invoked to account for the formation of diazepine 292 from the electrophilic diazoalkane substitution reaction of ethyl diazoacetate and dimethyl diazomethylphosphonate, with the 2,4,6-trimethylpyr-ylium salt 289 (337) (Scheme 8.70). While the expected 4-(diazomethyl)-47/-pyran 290 could be isolated (20-22%), the 2-substituted isomer 291 was not. It was proposed that this latter species underwent 671-electrocyclic ring opening followed... 

Nesvadba et al. (83CCC3307) also observed a very interesting expansion of the pyridinium ring when treating salts like 134 with alkaline ferricyanide. The condensed diazepines 135 are only formed if the 1-position in 134 is... 

Certain AMmines formed by deprotonation of N-aminoazolium salts also failed to undergo cycloaddition to give azapentalenes. TV-Amino-thiazolium mesylate on treatment with potassium carbonate and DMAD added 2 moles of dipolarophile to give the fused diazepine 219 2°5 4-Amino-l-methyl-s-triazolium iodide and DMAD in the presence of base gave the pyrazole 221, probably by ring opening of the first-formed adduct 220. Dehydrogenation to 222 did not occur.297... 

Dimerization of activated olefins or ketones as a means of ring closure was mentioned in Part I reports of more examples have been published.132 A special kind of coupling and ring closure occurs in the reduction of 6-phenyl-2,3-dihydrodiazepinium salt (76) in DMF to the diphenylpyrrolo-diazepine derivative (77). A plausible explanation of the formation of 77 involves dimerization of an initially formed radical, followed by intramolecular displacement of ethylenediamine.133-135... 

Reactions of hydrazine and methylhydrazine with pyrylium or thiinium salts, e.g. (137), provide major routes to H-1,2-diazepines (138) and l//-l,2-diazepines (139) (76H(4)1509, 80CJC494). 

H-1,2- Diazepines acylation, 7, 602 nucleophilic reactions, 7, 603 protonation, 7, 601 from pyrylium salts, 3, 660 4-subs tituted synthesis, 7, 604 synthesis, 7, 598, 599 thermal reactions, 7, 600... 

Reaction of 2.3-diamino-5-bromopyridinium perchlorate and acetyl-acetone4 or //-chlorovinylaldehyde13 did not provide the expected pyrido[2,3-/>](l,4)diazepines (II), but provided instead the pyrido[l,2- ]-pyrimidinium salts (12). 

Similar differences leading to pyridinium salts or diazepines have been observed in the reaction of monocyclic pyrylium salts with hydrazine [82AHC(Suppl)]. Diazepine 175 (R1 = Me, R2 = Et, Ar = Ver) is known as the tranquillizer drug Tophizopame (Gideon Richter, Hungary). 

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