Basicity of guanidines

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,... 

Similarly, strong bases will also have equal basicities in sufficiently acidic solvents. As shown in Fig. (3-3b), all bases stronger than the HO ion are adjusted to the basicity of this ion in water. Consequently, the effective basicities of guanidines and carbanions cannot be measured in water, but only in less acidic differentiating solvents such as liquid ammonia or diethyl ether. 

Table 2.10 Gas phase basicities of guanidine derivatives (kcal moG...

M. Eckert-Maksic, Z. Glasovac, P. Troselj, A. Kiitt, T. Rodima, I. and Koppel, LA. Koppel, Basicity of guanidines with heteroalkyl side chains in acetonitrile, Eur. J. Org. Chem. 30 (2008), pp. 5176-5184. 

The remarkable basicity of guanidine is attributed to the fact that the positive charge on the guanidinium ion is delocalized equally over the three nitrogen atoms, as shown by these three equivalent contributing structures ... 

Explain why the basicity of guanidine is comparable to that of an alkoxide ion. Where does protonation occur ... 

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. 

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. 

Some substituted guanidines have been obtained [457] by reaction of amines with the disulphide H2N(HN )C S S C( NH)NH2. Papers on the structure and p/fa s [458], and the synthesis [458, 459] of acylguanidines have been published. Reaction of guanidine with alkyl-, alkenyl-, and benzyl-halides, followed by distillation under basic conditions, is reported to give useful yields of amines [460]. A novel electrophilic substitution of benzene to give A -methyl-A -phenyl-guanidine amongst other products has been published [461 ]. 

Guanidines are basic molecules (pA of guanidine = 12.5) with a capacity to form intermolecular contacts mediated by H-bonding interactions. Consequently, they are potentially useful pharmacophores in medicinal chemistry, 1 have proven applications as artificial sweeteners,2,3 and are useful as probes in academic studies of intermolecular associations, including su-pramolecular complexes. Expedited access to these molecules via solid-phase synthesis is therefore a worthy goal. This chapter outlines various... 

The polar functionality presents a major problem in the synthesis of cylindrospermopsin because the natural product cannot be extracted into organic solvents, making its separation from water-soluble reagents difficult. Clearly, the sulfate ester should be introduced in the last step. The guanidine should also be introduced late in the synthesis and should be protected as a less basic acyl guanidine until as late as possible. Finally, the uracil is also polar and so must be either introduced late in the synthesis or protected as a dialkoxypyrimidine. 

Selective bromine-mediated addition of BOC-protected-guanidine 81 to dihydropyridine 56 occurs across the electron-rich 5,6-alkene to give, after acid deprotection, r-2-amino-l,3a,5,7a-dihydroimidazo[4,5-b]pyridine 82 (Scheme 23). Aminal bond cleavage under basic conditions affords substituted 2-aminoimidazole 83 <2004OL3933>. Replacement of guanidine 81 with urea or thiourea leads, similarly, to 2-aminooxazoles or 2-ami-nothiazoles, respectively however, the yields are considerably lower than that of 82 due to the sensitivity of the ureas to bromine oxidation <2005JOC8208>. 

So as to get the strongest possible basicity, these biguanides were prepared with the highest possible degree of N-alkylation. However, no satisfactory precedure was described in the literature. So original synthetic methods were devised for this purpose. These rely essentially on the addition of guanidines to carbodiimides or of amines to cationic dimeric carbodiimides.18... 

These biguanide-supported catalysts are far more reactive and more stable than the previously described guanidines.,7b This confirms the higher basicity of biguanides vs. guanidines and that their immobilisation induces only a very limited decrease in reactivity 90% instead of 94% yield after 30 mn reaction time. 

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