Cyanogen bromide Ring closure

Cyanogen bromide ring closure of (417) was used to prepare streptolidine lactam (418), a guanidine-containing amino acid lactam moiety of the streptothricin antibiotic group (77BCJ2375), that moiety being a 4,5,6,7-tetrahydroimidazo[4,5-c]pyridine. 

Reaction of yohimbine (74) with cyanogen bromide in ethanol-chloroform afforded an isomeric mixture of (3/ )- and (3S)-ethoxy-3,4-secocyanamide derivative (562 and 563, respectively) (277, 278). It was found that the relative amounts of 562 and 563 depend on the molar ratio of ethanol to the substrate applied during the reaction. Stereospecific ring closures of 562 and 563 with hot acetic acid yielded yohimbine and pseudoyohimbine (88), respectively. 

Reaction of 2-substituted 1,3-propanediamines 617 with carbon disulfide, followed by ring closure under micro-wave conditions gave 2-pyrimidinethiones 619, while reaction of the same diamines with cyanogen bromide in a one-pot microwave procedure gave cyclic guanidines 620 <2004JOC1571>. 

Allyl alcohols readily react with trichloroacetonitrile to give the corresponding trichloroacetimidates 145. Activation of the double bond with electrophilic reagents results in ring closure to yield oxazolines 146. The most commonly employed electrophiles include iodine, iodine monochloride, phenylselenyl chloride, and mercuric trifluoroacetate. Other nitriles including cyanogen bromide and N,N-dimethylcyanamide can also be used. Since oxazolines readily hydrolyze to amides, the net effect of this reaction sequence is to produce p-amino alcohols 147 from an allyl alcohol. This strategy has been employed in numerous total syntheses of natural products. Examples are listed in Table 8.18 (Fig. 8.7 Scheme 8.43). ° ... 

In the absence of a trichloromethyl group in the enamine structure, the process follows a different route. Thus, the cyanoacetic ester dimer reacts with cyanogen bromide at its active methylene group with a ring closure... 

The 3-amino derivative (126) could not be eiasily synthesized by the customary method of reacting 1-hydrazinoisoquinoline with cyanogen bromide but reaction of (127) with ammonium acetate in a sealed tube did form (126) as did ring closure of 1-hydrazinoisoquinoline with S-methylisothiourea (71CB3947). It was possible to perform the standard diazonium reactions with (126) (70UC894). 

This series of compounds is prepared by ring closure of the appropriate 4-hydrazino-1,2,4-triazines with carboxylic acids, carbon disulfide, cyanogen bromide, etc. to give the 3-unsubstituted or 3-substituted (alkyl, thiol, amino) derivatives (67CB3467,81JHC1353). 

Ring closure with cyanogen bromide CycUmmonium salts from di-tert-amines... 

Hydroxy-3-phenylthiopropylamine stirred ca. 20 hrs. with cyanogen bromide and Na-acetate as acid acceptor in methanol 2-amino-5-phenylthiomethyl-2-oxazoline. Y 88%. F. e. s. E. R. Freiter, A. H. Abdallah, and S. J. Strydcer, J. Med. Chem. 16, 510 (1973) with CICN, without acid acceptor, stereospecific ring closure with retention or inversion of configuration, interconversion of stereo-isomeric 2-aminoalcohols, s. H. Wollweber and R. Hiltmann, Arch. Pharm. 306, 284 (1973). 

---