Cyanogen bromide ureas

Cleavage of tertiary amines with cyanogen bromide (von Braun) Dehydration of disubstituted ureas... 

CARBONYL FLUORIDE UREA THIOUREA CYANOGEN BROMIDE CYANOGEN CHLORIDE... 

The cyclization of 285 proceeded similarly as in the synthesis of 278-281. The N,A-dimethyl-substituted amino ester 285 and cyanogen bromide resulted in 286, and subsequent acid hydrolysis led to the urea ester 287, which was cyclized to l-methylperhydro-2,4-quinazolinedione 288 at elevated temperature [69LA(728)64]. 

Cyanogen bromide cleavage of the polypeptide subunit should yield 4 peptides if the subunit contains 3 methionines (Table III). Cleavage products were isolated by gel filtration through Sephadex G-75 columns and analyzed for purity with polyacrylamide gel electrophoresis in 8 M urea containing 0.1 M thioglycolate. Four peptide products were obtained (34). 

The 1,3,6-benzotriazocine ring system was first synthesized by Hornyak, Lempert, and co-workers, who found that N-tosyl-o nitroanilines could be haloalkylated and then aminated to yield compounds 234 (R = H, Me R = H, Me, OMe). Hydrogenation of 234, followed by reaction with orthoesters, R2C(OAlk)3, produced compounds 235 (R = R2 = H, Me R1 = H, Me, OMe). If cyanogen bromide was used instead of orthoesters, triazocines 235 (R2 = NH2) resulted. Reduction of 234 (R = R = Me), followed by condensation with diethyl carbonate, gave urea 234 (R = R = Me, X = O). A similar reaction starting with 234... 

An efficient, practical solid-phase synthesis of a variety of bis-hetero-cyclic compounds was developed starting from resin-bound orthogonally protected lysine (Fig. 10). Tetraamines 36 were synthesized by exhaustive reduction of resin-bound tetraamides 35. Cyclization with different commercially available bifunctional reagents such as cyanogen bromide, thio-carbonyldiimidazole, carbonyldiimidazole, and oxalyldiimidazole yielded the corresponding bis-heterocyclic compounds bis-cyclic guanidines 37,39 bis-cyclic thioureas 38, bis-cyclic ureas 39, and bis-diketopiperazines 40, respectively.40 Reduction of compounds 40 led to bis-piperazines 41. 

Demethylation at the nitrogen in position 6 could be realized by new modifications of the von Braun degradation. The 6-nor-6-cyano derivatives 46, obtained in the usual way by the action of cyanogen bromide on the parent compounds, could be reduced directly with zinc in acetic acid in good yield (46) to the 6-nor compounds (47). An alternative procedure was published independently by a Japanese group (47), using a two-step process via a urea-type compound 48. 

The synthesis of 2(3//)-oxazolones by incorporation of carbon atom 2 into a four-atom chain is exemplified by the condensation of phenacylaniline with ethyl chloroformate (equation 138). Benzoxazolones are similarly prepared from o-aminophenols and derivatives of carbonic acid, such as phosgene, diethyl carbonate, urethane (Et02CNH2) or urea (equation 139). The analogous condensation of carbon disulfide or cyanogen bromide with o-aminophenols leads to benzoxazolethiones or 2-aminobenzoxazoles, respectively (equation 140). 

Cyanogen bromide converts acetyl-a-codeimethine to cyanonoracetyl-a-codeimethine [lvii, R = Ac] [33, 78] acetyl-)3- and y-codeimethines behave likewise, [lvh, R = Ac] is saponified to a-cyanonorcodei-mothine [lvh, R = H], whilst the -derivative gives the urea [nvm]... 

Microwave irradiation can be used to make oxazolo[4,5-fc]pyridines and allows reaction with amides in lieu of acids when urea or thiomea are used, 2-ones (2-thiones) are obtained carbon disulfide with potassium hydroxide also leads to 2-thiones. The use of triphosgene and 2,3-diamino-pyridines can be used to made the analogous imidazo[4,5-b]pyridin-2-ones. Reaction with cyanogen bromide gives... 

---