Guanidine nucleophilic base

Morpholine followed by a soln. of guanidine as a strong, weakly nucleophilic base in abs. ethanol added to a hot soln. of the startg. pyrimidinone in the same solvent, and refluxed 18 hrs. -> product. Y 70%. F. e., also ring expansion (cf. Synth. Meth. 16, 503), s. J. Ashby and D. Griffiths, Soc. Perkin I 1975, 657. 

The group proposed that the hydrocyanate underwent a formal Brpnsted base interaction with the guanidine catalyst, thus activating the nucleophile for addition (Fig. 9). In contrast to the bifunctional catalysts, the guanidines are basic enough to activate the substrates without the need for secondary moieties. 

The combination of his-electrophilic and his-nucleophilic components is the basis of general pyrimidine synthesis. A reaction between an amidine (urea or thiourea or guanidine) and a 1,3-diketo compound produces corresponding pyrimidine systems. These reactions are usually facilitated by acid or base catalysis. 

Pd(0)/phosphine complexes, or their precursors, in the presence of a suitable co-base, have also been shown to promote, in good yields (66-100%), the formation of allylic carbamates from various primary and secondary aliphatic amines, pressurized C02 and allylic chlorides, in THF, at ambient temperature [87a]. The choice of the added co-base (Base), used for generating the carbamate salt RR NC02 (BaseH)+, was found to be critical for high yields of O-allylic urethanes. The use of a guanidine (CyTMG) or amidine (DBU) base was optimal for this system (see also Section 6.3.1). ft is assumed that this chemistry passes catalytically through a mechanism similar to that illustrated in Scheme 6.19. This involves nucleophilic attack by carbamate anion on a (tt-allyl) palladium species, formed by the oxidative addition of the allylic chloride to a palladium(O) intermediate. 

Amidines and guanidines are slightly more basic than aliphatic amines, and steri-cally crowded amidines (e.g. DBU) or guanidines are often used to mediate dehydro-halogenations. Conditions can, however, sometimes be found which lead to the N-alkylation of these organic bases (Scheme 6.30). Identification of appropriate conditions for such reactions is mostly empirical, because small changes can have important but unforeseeable effects on the selectivity of a reaction (compare, e.g., the first and second reactions in Scheme 6.30). If the reactivity of a given substrate is too low, its nucleophilicity can be enhanced by deprotonation. 

Where R4 is a hydrogen or carbon atom, 10.15 is simply an amidine. However, urea 10.16, thiourea 10.17, or guanidine 10.18 and their derivatives may be used. These nucleophiles may be condensed with ester and nitrile functionalities as well as with aldehydes and ketones. Such condensations to afford pyridimidine derivatives are usually facilitated by acid or base catalysis, although certain combinations of reactive electrophilic and nucleophilic compounds require no catalyst at all. Some examples are shown below. 

All known compounds of this type have the 2V-amino group in position 4. The main methods of synthesis are based on cyclization reactions of diamino- and triamino-guanidines. Since the latter have several unequal nucleophilic centers, reactions often give a poor yield of the corresponding 7V-aminotriazole. 

A carboxylic acid derivative which also contains an activated neighbouring halo atom may be cyclized by warming with an amidine (or guanidine) or 2-aminopyridine (a cyclic amidine). In some reactions of this type, it is advantageous to add a base such as TEA. The chlorine atom of the thienopyridine (6[Pg.422]

Guanidine participating organic reactions could be schematically classified into two types of reactions catalytic and stoichiometric, in which a guanidinium salt composed of guanidine like 2 and either an acid or nucleophile plays an important role as a common active complex. In the former type of reaction, 2 is repeatedly used as a free base catalyst, whereas a guanidinium salt is formed in the latter (Figure 4.2). 

A recently reported synthesis of 3-amino-l,2,4-benzotriazines is also based on the [3+3] combination of fragments (Scheme 124) <2006RCB1243>. The feature of this approach is that in 3-fluoro-substituted nitrobenzenes, nucleophilic displacement of hydrogen at C-2 or C-6 by the action of guanidine takes place, followed by intramolecular cyclization into the isomeric 3-amino-l,2,4-benzotriazines (Scheme 124) <2006RCB1243>. 

Organocatalysts As mentioned earlier, organocatalytic ROP was first reported applying pyridines as the nucleophilic catalyst. Subsequently, guanidine, amidine, and thiourea-based organocatalysts were found to be highly active for the ROP of lactones [40-42],... 

The guanidine derivative (115) bearing N-Boc groups have been found that acted as reactive nucleophiles in the enantioselective allyhc substitution to give monoallylated or bisallylated products (116) in the presence of iridium-complex based on the chiral pybox ligand (Scheme 27)." ... 

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