Ureas thioureas

Acetoiicetyliition Reactions. The best known and commercially most important reaction of diketene is the aceto acetylation of nucleophiles to give derivatives of acetoacetic acid (Fig. 2) (1,5,6). A wide variety of substances with acidic hydrogens can be acetoacetylated. This includes alcohols, amines, phenols, thiols, carboxyHc acids, amides, ureas, thioureas, urethanes, and sulfonamides. Where more than one functional group is present, ring closure often follows aceto acetylation, giving access to a variety of heterocycHc compounds. These reactions often require catalysts in the form of tertiary amines, acids, and mercury salts. Acetoacetate esters and acetoacetamides are the most important industrial intermediates prepared from diketene. 

The simplest [3 + 3] reactions in the pyridine series involve reaction of o-chloropyridinecarboxylic acid derivatives with three-atom fragments such as urea, thiourea(s), amidines and guanidines, e.g. (240) (241). Examples are known mainly in... 

Several related derivatives have also been utilized in this type of synthesis. Imino-chloromethanesulfenyl chlorides (184), prepared by the controlled addition of chlorine to isothiocyanates, react with amidines (161) to give 1,2,4-thiadiazolines (185) (71T4117). Chlorocarbonylsulfenyl chloride (186), prepared by the hydrolysis of trichloromethanesulfenyl chloride with sulfuric acid, reacted with ureas, thioureas and guanidines to give 1,2,4-thiadiazolidine derivatives (187) <70AG(E)54, 73CB3391). 

Decorative laminates have a core or base of Kraft paper impregnated with a phenolic resin. A printed pattern layer impregnated with a melamine-formaldehyde or urea-thiourea-formaldehyde resin is then laid on the core and on top of this a melamine resin-impregnated protective translucent outer sheet. The assembly is then cured at 125-150°C in multi-daylight presses in the usual way. 

Cleavage with thioacids IRCOSH) results in the formation of amides, R 2NC(0)R. The concept was extended to the formation of ureas, thioureas, and thioamides. ... 

Condensation of 165 with ethoxymethylenemalononitrile gave 171, and with ethyl ethoxymethylenecyanoacetate or methyl bis(methylmercapto)-methylene cyanoacetate it yielded 172 (80AP108). The reaction of 172 with urea, thiourea, and benzyl nitrile afforded 173 (91PHA98). Treatment of hydrazino derivatives 165 with alkyl, aryl, or aralkyl isothiocyanates yielded (86JHC1731) 3-(/V-substituted-thiocarbamoyl)-hydrazino[l,2,4]triazino[5,6-b]indoles which have been evaluated for in vitro antimicrobial activity (Scheme 36). 

Not only N-H bonds from amines can participate in the aminolysis reaction, but also less nucleophilic urea, thiourea and biuret NH units can react with halophosphanes in an effective manner, forming the corresponding phosphinous amides with additional functionalities at the nitrogen atom [39-44]. 

Several metal complexes have been described with urea, thiourea or dimethyl derivatives [49,50]. We will focus in this section on the coordination chemistry of substituted ureas and thioureas used as neutral Ugands as well as many ureato and thioureato anions complexed to metal centres. 

Thiourea and selenourea both form canal inclusion compounds. The selenourea compounds, reported only briefly 37), appear to be isostructural with the rhombo-hedral thiourea compounds, although with larger dimensions which are more susceptible to the sizes of guest molecules. For urea, thiourea and selenourea the crystal densities of the compounds are significantly less than those of the hosts values (g cm - 3) for the pairs host/complex are 1.30/1.20 1.40/1.10 2.08/1.60-1.65 for urea, thiourea, selenourea, respectively37). 

With this set of five optimized reaction conditions in hand (Fig. 5.6), the production of a small DHPM library was performed. As a set of structurally diverse representative building blocks, 17 individual CH-acidic carbonyl compounds, 25 aldehydes, and 8 ureas/thioureas were chosen. Combination of all these building blocks would lead to a library of 3400 individual DHPMs. To demonstrate the practicability of the presented concept, a representative subset library of 48 DHPM analogues involving all of the aforementioned building blocks was generated [2],... 

Amidines and cyclic amidines are also converted into 1,2,4-thiadiazoles by reaction with isothiocyanates, imino-sulfenyl chlorides, di- and trichloromethyl sulfenyl chlorides, and carbon disulfide in the presence of sulfur. Ureas, thioureas, guanidines, carbodiimides, and cyanimides react with chlorocarbonylsulfenyl chloride to produce 1,2,4-thiadiazol-5-one derivatives in another example of a type B synthesis <1996CHEC-II(4)307>. 

The reaction of 2,5-dimercapto-l,3,4-thiadiazolidine 34 with dialkylamines under Mannich reaction conditions gave N,S-aminomethylated thiadiazoles in 69-70% yields (Equation 24) <1998CHE1431>. With urea, thiourea, semicarbi-zide, or thiosemicarbazide, thiadiazolidine 34 gave N,N-aminomethylated thiadiazoles in 89-98% yields (Equation 25). 

R, Thaimattam, D. S. Reddy, F. Xue, T. C. W. Mak, A Nangia, G. R. Desiraju, Interplay of strong and weak hydrogen bonding in molecular complexes of some 4,4 -disubstituted biphenyls with urea, thiourea and water , J. Chem Soc, Perkin Trans. 2,1998,1783-1789. 

The reactions of 5-acyl-2,2-dimethyl-4,6-dioxo-l, 3-dioxanes (1373) with urea, thiourea, sulfamide, hydroxylamine, or 1-substituted hydrazines gave monocyclic six- and five-membered heterocycles (1374-1378) in good yields [79JAP(K) 106466],... 

CARBONYL FLUORIDE UREA THIOUREA CYANOGEN BROMIDE CYANOGEN CHLORIDE... 

SCH 28191 (experimental drug) Probe 6. beta-carotene Probe 7. LDH isoenzymes Probe 8. HGH tryptic digest Probe 9. urea, thiourea Probe 10. tricyclic antidepressants Probe 11. avermectins... 

Elution curves for biguanide in the presence of related compounds (e.g. cyanamide, cyanoguanidine, guanidine, urea, thiourea) have been established (690). Various ion-exchange resins are suitable (108,686,689). 

Ethyl 2-ethylthio-4-chloro-5-pyrimidinecarboxylate (XXIIa), as well as the corresponding4-hydroxy-(XXIIb) and 4-amino-(XXIIIa) derivatives, possess-anti-cytogenic activity on Neurospora crassa [223, 224]. Compounds (XXIIIa, b and c) were found to inhibit the conversion of orotic acid to the uridine nucleotides [202]. Ethyl 2-methylthio-4-(halo-substituted anilino)-5-pyrimidinecarboxylates (XXIV), particularly the o-bromo- and the o-chloro- derivatives, substantially inhibit the growth of five experimental mouse tumours (Krebs-2 ascites carcinoma, Ehrlich carcinoma clone 2, leukaemia L-1210, carcinoma 755 and lymphocytic neoplasm P-288) [225]. Compounds of this type are usually prepared by the base catalysed condensation of ethoxymethylenemalonic esters or related derivatives with urea, thiourea, guanidine, or substituted amidine-type analogues [212, 225-237]. 

Jacobsen (1998), Corey (1999) chiral ureas/thioureas and guanidine Enamine Cataiysis... 

As a true testament to the potential long-term impact of H-bonding activation, a number of ureas, thioureas, and acid catalysts are now finding broad application in a large number of classical and modem carbon-carbon bond-forming processes. On one hand, Johnston s chiral amidinium ion 28 was elegantly applied to the asymmetric aza-Henry reactions (Scheme 11.12d). On the other hand, chiral phosphoric acids (e.g., 29 and 30), initially developed by Akiyama and Terada, have been successfully employed in Mannich reactions, hydrophosphonylation reac-tions, aza-Friedel-Crafts alkylations (Scheme 11.12e), and in the first example... 

Berkessel and co-workers have demonstrated the utility of the bifunctional cyclohexane-diamine catalysts in the dynamic kinetic resolution of azalactones (Schemes 60 and 61) [111, 112]. The authors proposed that the urea/thiourea moiety of the catalyst coordinates and activates the electrophilic azlactone. The allyl alcohol nucleophilicity is increased due to the Brpnsted base interaction with the tertiary amine of the catalyst. 

II 1 A -Melhylformamide A, A -Dimethylformamide Benzamide Methyl dimelhylcarbamate Urea Thiourea... 

Bipyridine and 4,4 -bipyridine form molecular complexes with halo-genated nitrophenols." " The former also complexes with urea, thiourea and related compounds," benzyl alcohol, phenol," acetic... 

In most of these reactions, it is nitrogen of a urea, thiourea, isothiourea, or an amidine which is the nucleophile for the addition to an appropriately situated electrophilic carbon. Conditions which enhance the electrophilic character of the carbon, or the nucleophilicity of the nitrogen, promote cyclization. Most commonly, this cyclization is affected by nitrogen addition to the electrophilic / -carbon of a Michael acceptor, and can be performed under acid or basic conditions. 

---