Guanidine, basicity

The required triamino-4(3H)-pyrimidinone is prepared in three steps starting from guanidine [50-01-1] (14) (26). Condensation with methylcyanoacetate [105-34-0] (15) under basic conditions, followed by nitrosation of the intermediate [56-06-4] (16), gives... 

NaBH4, LiCl, diglyme. A diacylated guanidine was not deacylated under these conditions, whereas the usual basic conditions for acetate hydrolysis also resulted in guanidine deacylation. ... 

In a similar way, 3-amino-1,2,4-triazino[6,5-c]quinoline 4-oxides 127 were synthesized by the reaction of 4-chloro-3-nitroquinoline 128 with guanidine, followed by the cyclization of intermediate arylguanidines under basic conditions (81JHC1537). 

One of the standard methods for construction of the basic heterocyclic ring was elaborated not long after the turn of the century. Thus, condensation of ethyl lactate with guanidine leads to the imine of the desired ring system (47), possibly by a reaction scheme such as that outlined below. Hydrolysis affords the oxazolidinedione (48). Methylation in the presence of base gives 49. 

The reaction of N-amino heterocycles 759 and 760 with diaryl carbodii-mide gave triazolotriazine 761 in good yield. In some cases the intermediate guanidines are isolated which by thermal or basic treatment cyclized (86H3363 89H1607) to neutral or mesoionic compounds. 

Benzoguanamine has been prepared by the reaction of dicyandiamide with benzonitrile in a sealed tube at 220-230°,2 with an excess of benzonitrile in the presence of piperidine and potassium carbonate,3 with benzonitrile in a solvent in the presence of a basic catalyst,4 and with benzamidine hydrochloride at elevated temperatures.5 It has also been prepared from the reaction of biguanide acetate with benzamidine hydrochloride,5 or of bigua-nide sulfate with benzoyl chloride in an alkaline medium,7 and by the distillation of guanidine benzoate.5... 

Completion of the total synthesis afforded only six further steps, including the installation of the second 2-aminopyrimidine ring via a second domino sequence. This process presumably involves a conjugate addition of guanidine (2-293) to the enone system of2-292, followed by a cyclizing condensation and subsequent aromatization. Under the basic conditions, the ethyl ester moiety is also cleaved and 2-294 is isolated in form of the free acid, in 89 % yield. Finally, decarboxylation and deprotection of the amino functionality yielded the desired natural product 2-295. 

Protocols for guanidination reactions typically use basic conditions to deprotonate all the lysine s-amino groups, which is necessary to achieve efficient yields. The amount of N-terminal... 

Arginine is another example of an a-amino acid in which guanidine and amine functions are separated by a chain of four carbon atoms. Raczynska and coworkers86 suggested that the strong gas-phase basicity of arginine (comparable to the GB of DBN) may be due to the internal solvation of the guanidinium cation, 48. 

The effect of steric hindrance on the rates and kinetic isotope effects for reactions of l-nitro-l-(4-nitrophenyl)alkanes and their deuterated analogues with two bicyclic guanidines of comparable basicity (l,5,7-triazabicyclo[4.4.0]dec-5-ene, TBD, and its 7-methyl derivative, MTBD) in THF has been studied. The results disagree with the notion that deuterium kinetic isotope effects are enhanced by steric hindrance, since for the reactions of MTBD with various carbon acids the KIEs decrease with steric hindrance in the carbon acid but the converse is true for reactions of TBD. 

The even greater basicity of guanidine (p/iLa = 13-6) as compared with amidines is due to an even greater resonance stabilization of the cation, since three equivalent resonance structures enter into resonance [6]. The base itself resonates between three nonequivalent structures [37], and has according to Pauling (1939,... 

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