C—N cleavage

Phenolic aldehydes can be obtained by the Duff reaction, in which the phenol is heated with urotropine, boric acid, and glycerol for 30 minutes at 150-160° 857 the yields are not high (15-20%), but the procedure is simpler and less time -consuming than the Reimer-Tiemann synthesis the products are the ortho-derivatives. Dialkylanilines can be formylated in the same way,858 but here the products are the para-aldehydes. 

Besides the methods described above for forming new carbon-carbon bonds with elimination of elemental nitrogen or an amine there are other processes in which other nitrogenous compounds are eliminated. For example, Rinkes859 obtained ethyl 2-phenyl-1-pyrrolecarboxylate by treating ethyl 1-pyrrole-carboxylate with A-nitrosoacetanilide  

a synthesis of azulene that gives good yields starts from the fulvene derivative860 that is formed quantitatively from cyclopentadiene and penta-nedial A-methyl-A-phenylmonoimide  

Finally there is the reaction of tetramethylformamidinium chloride with hydrogen cyanide at 0-10° which gradually yields (dimethylamino)malon-dinitrile in 92% yield 861 

There are only a few examples of this type of reaction. When 2-naphthol is heated with mercaptoacetic acid in ethylene glycol at 145-150°, hydrogen sulfide is eliminated and 2-hydroxy-1-naphthaleneacetic acid is formed in 89% yield.862 When thiophenol reacts with tert-butyl phenyl sulfide under catalysis by boron trifluoride, / -(terf-butyl)thiophenol is formed in yields of up to 81% and a different molecule of thiophenol is eliminated (it is an apparent rearrangement).863 

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In contrast to the well-defined photochemical behavior of 1-azirines the thermal reactions of these compounds have been studied less thoroughly (68TL3499). The products formed on photolysis of azirines can best be rationalized in terms of an equilibration of the heterocyclic ring with a transient vinylnitrene. Thus, products formed from the thermolysis of azirines are generally consistent with C—N cleavage. For example, the vinylnitrene generated from the thermolysis of azirine (149) can be trapped with phosphines (72CCS6S). 

Harper DB (1977) Microbial metabolism of aromatic nitriles. Enzymology of C-N cleavage by Nocardia sp. (Rhodochrous group) NCIB 11216. Biochem J 165 309-319. 

Predictably, 1,2,4-triazole is alkylated preferentially at the 1-position [36, 38,39]. Specific alkylation at the 4-position can be achieved by the initial reaction with dibromomethane to form the bis-triazol-l-ylmethane (see below), followed by quat-emization of the triazole system at the 4-position and subsequent C-N cleavage of the 1,1 -methylenebistriazolium salts [40]. 1,2,3-Benztriazole yields a mixture of the isomeric 1- and 2-alkylated derivatives [41]. The 1-isomer predominates, but the ratio depends on whether the reactions are conducted in the presence, or absence, of a nonpolar organic solvent (Table 5.33). Higher ratios of the 1-isomer are obtained under solidrliquid two-phase conditions. Thus, alkylation of 1,2,3-benztriazole with benzyl chloride produces an overall yield of 95% with the l- 2-isomer ratio of ca. 5.7 1 similar reactions with diphenylmethyl and triphenylmethyl chlorides gives overall yields of 95% (9 1 ratio) and 70% (100% 1-isomer), respectively [38], 6-Substituted purines are alkylated at the N9-atom and reaction with 1-bromo-3-chloropropane yields exclusively the 9-chloropropyl derivative (cf. reaction wi phenols) [42]. 

Under favourable circumstances, the initially formed /V-ylid reacts further through C-N cleavage. Thus, in the presence of a strong nucleophile, such as a phenoxide anion, the quaternary dichloromethylammonium cation forms an ion-pair with the phenoxide anion (Scheme 7.27), which decomposes to yield the alkyl aryl ether and the /V-formyl derivative of the secondary amine [22, 23]. Although no sound rationale is available, the reaction appears to be favoured by the presence of bulky groups at the 4-position of the aryl ring. In the absence of the bulky substituents, the Reimer-Tiemann reaction products are formed, either through the breakdown of the ion-pair, or by the more direct attack of dichlorocarbene upon the phenoxide anion [22,23],... 

Use has been made of the C-N cleavage in the conversion of the bicyclic tertiary amines, derived from the 4tc + 2tc cycloaddition of pyrroles and isoindoles with benzynes, into aromatic systems, e.g. naphthalen-l,4-imines and anthracen-9,10-imines yield naphthalenes and anthracenes with the extrusion of the nitrogen bridge [24] in yields which are higher than those obtained by standard oxidation procedures. 

The anticonvulsant agent primidone (4.246) is the 2-dihydro derivative of phenobarbital (4.247), which is one of its metabolites. The second major metabolite, 2-ethyl-2-phenylmalondiamide (4.248), is produced by a double C-N cleavage [160]. The profile of plasma levels in rats strongly suggests that 2-ethyl-2-phenylmalondiamide is not derived from the metabolite phenobarbital, but directly from primidone. Indeed, a C(2)-hydroxylated metabolite serves as an intermediate for both detected metabolites (see also Chapt. 6 in [21]). N-Alkyl derivatives of primidone yield a greater proportion of ring-opened metabolites, an observation explained by their higher susceptibility to oxidative metabolism at C(2) [161]. 

An electrochemical reaction on the azepine carbamates 19 resulted in a ring contraction to give the N-substituted anilines 20 in moderate yield (Equation 1). Mechanistically, initial oxidation of the carbamate to give the radical cation 21, followed by electrocyclic rearrangement to 22, C-N cleavage, and then reduction was proposed <1998H(48)1151>. 

Whether these radicals serve as electron donors (to yield iminium cations) or as hydrogen atom donors (to yield vinylamines) will depend on the nature of the reaction partner, particularly on its reduction potential. In any case, the quantum yield of C N cleavage reactions are low, since they require several consecutive processes, i.e. successive transfer of an electron, a proton, and a second electron, or a mechanistic equivalent thereof. 

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