Urea and Thiourea Derivatives

8 Amendola, V., Esteban-Gomez, D., Fabbrizzi, L. and Licchelli, M., What anions do to N-H-containing receptors , Acc. Chem. Res. 2006, 39, 343-353. 

---

Chiral amines and diamines are readily available substrates for the synthesis of ligands for transition metal-catalysed reactions since they can easily be transformed into chiral ureas and thioureas. Therefore, several groups have prepared chiral symmetrical ureas and thioureas, dissymmetrical ureas and thioureas, amino-urea and thiourea derivatives. Finally polyureas and non-soluble polythioureas were also prepared and tested as ligands for asymmetric catalysis. 

Moreau and co-workers have also prepared (ll ,2K)-l,2-diaminocyclo-hexane amino-urea and thiourea derivatives [43]. Diphenylethylenediamine-substituted monothioureas are more stable than the cyclohexyldiamine counterpart, but they can also rearrange to guanidine derivatives, especially at high temperature or in the presence of metal [43]. Under the same conditions, thioureas also rearrange to guanidines in the presence of amines. Selective formation of substituted guanidines from thiourea derivatives of diaminocy-clohexane or diphenylethylenediamine were also reported in a recent paper from Ishikawa [44]. 

The reaction was first tested with these substances as ligands but the organic molecule, in the absence of any added metal ion, proved to be the most enantioselective catalyst (library 1 19% ee vs. less than 13% ee for the best metal catalyst). The effects of selective variations of the amino acid nature and of the salicylidene moiety on the diamine structure were investigated for urea and thiourea derivatives via HTS (library 2 48 urea compounds and... 

Finally, nitrone cyanation were performed with non-chiral urea and thiourea derivatives, the latter being more efficient for this process. No chiral compound has been described yet (Scheme 41) [ 159]. 

Most hydrogen-bond-containing crystal structures are homomolecular, i.e. both the hydrogen-bond accepting and donating functionality exist in the same molecule. Examples of such co-crystals are urea and thiourea derivatives as well as non-cyclic imides156,179,180. 

Since Curran and Kuo and Schreiner and coworkers reported that urea and thiourea derivatives act like Lewis acid catalysts, several chiral urea and thiourea catalysts have been designed by Jacobsen et al. and Takemoto et al. ... 

Interestingly, completely different types of organocatalyst have been found to have catalytic hydrocyanation properties. Among these molecules are chiral diketo-piperazine [4, 5], a bicydic guanidine [6], and imine-containing urea and thiourea derivatives [7-13]. All these molecules contain an imino bond which seems to be beneficial for catalyzing the hydrocyanation process. Chiral N-oxides also promote the cyanosilylation of aldimines, although stoichiometric amounts of the oxides are required [14]. 

The reaction of urea (and thiourea) derivatives with a-hydroxy-ketones yields imidazoles. Thus, condensation of benzoin with N-pheny 1 thiou rea in hexanol in the presence of catalytic quantities of HC1 (or dry HC1) gives l,4,5-triphenylimidazole-2-thione (21) in 50-60% yield.100... 

S. Wishkerman, J. Bernstein, M.B. Hickey, Crystal engineering with cocrystals of benzo-[18]crown-6 and urea and thiourea derivatives, Cryst. Growth Des. 9 (2009) 3204-3210. 

In a subsequent study, the synthesis of urea and thiourea derivatives of types 3a and 3b were undertaken in an attempt to obtain new hosts that might yield more stable complexes with glutamic acid (of types 4a and 4b) and that might, in fact, hold together in polar solvents. The rationale for the design was based on the previously documented observation that both 1,3-dimethylurea and 1,3-dimethyl-thiourea form stable host-guest complexes with acetate in deutero-dimethyl sulfoxide the K values for the latter are 45 dm moF and 340 dm moF , respectively. 

Lejohn, H. B., A rapid and sensitive auxin binding system for detecting N6-substituted adenines, and some urea and thiourea derivatives, that show cy-tokinin activity in cell division tests, Can. J. Biochem., 53[7], 768,1975. 

Several authors established the sterilising activity of urea and thiourea derivatives such as 4-imidazolidin-2-one (31) (Flint et al.. 1968 Simkover, 1964),... 

X-Ray analy.ses have been performed on salts of diphenyl phosphoric, phenylphosphonic, and trichloromethylphosphonic acids " phosphorylated urea and thiourea derivatives phenyl[[ -acetyloxy(4-nitrophenyl)]methyl]phosphinic acid ... 

Figure 9.4 (a) pKa values of urea and thiourea derivatives (b) resonance forms of thiourea ... 

The synthesis of p-o-glucopyranosyl-thioureas has been reported. N -Glucosylated sugar urea and thiourea derivatives such as 42 were synthesized by PhsP-induced condensation of the corresponding protected 6-azido-sugar with tetra-O-acetyl-p-D-glucopyranosyl isothiocyanate followed by either hydrolysis (HOAc, H2O) or thiolysis (H2S, silica gel), respectively, then deprotection. Acetylation of such doubly substituted thiourea derivatives led to various re-gioisomeric N- and S-acetylated derivatives. ... 

N-Lactosyl-urea and -thiourea derivatives have been obtained by condensation of lactosylamlne with long chain isocyanates and Iso-thlocyanates respectively. Muramoyl dipeptlde analogues (2) and (3) in which the sugar Is Joined to the peptide by a glycosylamine... 

Tang and coworkers" used bifunctional urea and thiourea-derived orga-nocatalysts (4a,b) for the Michael addition of cyclohexanone to nitro-olefins (Scheme 9.29). Using pyrrolidine-thiourea 4b afforded the desired y-nitroalkanes with high diastereo- and enantioselectivity under solvent-free conditions (up to 99 1 dr, 88-98% ee). Subsequently, Xiao and coworkers screened various bifunctional pyrrolidine-thiourea organocatalysts and identified 4c to be efficient at catalysing the Michael addition of various ketones to nitrostyrenes. Comparable results were observed (up to 99 1 dr and 99% ee) when the reactions were performed in both aqueous media and organic solvents. 

---