Guanidine-thiourea catalysis

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. 

Pyran-4-ones, chromones and flavones are converted into pyrimidines, usually under base catalysis, by reaction with compounds which contain the grouping N—C—N urea, thiourea, guanidine, aminoguanidine, acetamidine and dicyandiamide are examples of this type. Scheme 24 shows some typical examples (77BSF369, 81JHC619). 

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. 

Compounds 40 react with guanidine, urea, thiourea, methylisothiourea, guanylthiourea by Lewis-acid catalysis (00S1738) and with thiosemicarbazide, semicarbazide (99IZV361) in the presence of triethylamine to form the corresponding 5,6-oligomethylenepyrimidines and 3-hydroxy-2(thio)-carbamoyl-3-polyfluor-o a 1 k y 1 - 3.3 a. 4.5.6.7 - h e x a h y d r o - 2 / /- i n d a z o 1 e s 41, respectively (Scheme 38). The structure of 41 (thio) is confirmed by X-ray analysis. 

The concept of bifunctional catalysis as advanced for the natural cinchona alkaloids and cuprei(di)nes has resulted in the design and synthesis of a range of new cinchona derivatives. The major part of these novel organocatalysts are urea and thiourea cinchona derivatives together with cinchona alkaloids modified with, for example, a sulfonamide, squaramide, or guanidine group (Figure 6.8). 

The r-butoxycarbonylation of the sodium salt of thiourea does not require DMAP catalysis. The resulting N,N -bis t-butoxycarbonyl)thiourea reacts with amines to give bis(t-butoxycarbonyl)guanidines (eq 25). ... 

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