1,3-Diarylureas

The chlorosulfonation of Ar,Ar -diphenylurea 389 with excess chlorosulfonic acid is reported to yield the 4,4 -disulfonyl chloride Cremlyn et al.  

2 -Dimethyl- and 3,3 -dimethyldiphenylurea both react with chlorosulfonic acid (six equivalents) at 80-85 °C to give moderate yields of the corresponding 4,4 -disulfonic acids. 

It is interesting that although -diphenylurea reacts with excess chlorosulfonic acid to give the 4,4 -disulfonyl chloride, the 2,2 - and 3,3 -dimethyldi-phenylureas, on similar treatment, only gave the disulfonic acids. The difference in behaviour is probably due to the steric effects of the methyl groups inhibiting 

Some diarylthioureas have been treated with chlorosulfonic acid thus N-phenyl-A -(2-pyridyl)- and iV-phenyl-A -(2-thiazolyl) thioureas 394 and 395 afforded the corresponding 4 -sulfonyl chlorides. . /V-Phenyl-A -(2-pyridyl)-thiourea 394, unlike the analogous urea 391, did not yield the 2, 4 -disulfonyl chloride and only gave the 4 -sulfonyl chloride. The larger steric size of the sulfur as compared with the oxygen atom presumably caused too much steric hindrance at the ortho-position of the phenyl ring to permit disulfonation.  

The ionization of ureas, carbazides, carbazones and their thio analogues was studied in chlorosulfonic acid by conductivity, NMR and UV spectral measurements. The results indicated that thiourea is monoprotonated on the sulfur atom. The latter observation may account for the abnormal behaviour of phenylthiourea on treatment with chlorosulfonic acid. 

---

The diarylurea is insoluble in boiling water and is therefore easily separated from the monoarylurea, which is readily soluble. The proportion of diarylurea is highest for aniline and decreases with substituted anilines. 

Direct dyes of the disazo diarylurea type, such as Cl Direct Orange 26 (3.5) and Cl Direct Red 79 (3.21), are particularly prone to decomposition in high-temperature dyeing because molecular breakdown can occur by hydrolysis as well as by the reductive mechanism under alkaline conditions. Thus the ureido linkage in this red dye may be broken by hydrolysis to give two monoazo dye fragments (3.22), or the azo groups can be reduced to yield a diaminodiphenylurea (3.23) and two molecules of H acid (Scheme 3.3). 

The neutral alkali metal salts of benzohydroxamic acids have been found to undergo an unprecedented rearrangement to A(,A( -diarylureas. 2 side reaction, producing /9-alanine derivatives by way of a Lossen rearrangement, has been observed to accompany the hydrolysis of alkyl succinimidyl carbonates in basic aqueous buffers (see Scheme 97). The development of a modified Lossen rearrangement, whereby... 

Diesters are malonates, and are often used for the synthesis of barbiturates. Malonyl dichlorides can be used in place of a malonyl diesters, in which case the reaction can be performed at room temperature, as demonstrated by the synthesis of A-phenyl and A -pyridyl 2-thiobarbituric acids 666 from malonyl dichloride 664 and A, iV -diarylureas 665 <2002AJC287>. 

Preparation of diarylureas by the reaction of amines with potassium O-ethyl monothiocarbonate and dicarbethoxydisulfide [98]. 

Earlier it was reported that hydrogen peroxide and cumene hydroperoxide improve the yields of 1,3-diarylureas from the reaction of weakly basic aromatic amines with carbonyl sulfide at elevated temperatures [80]. The results are summarized in Table X. 

A number of thiadiazolidines supposedly obtained by Chakrabarti and De80, 65b by the action of alcoholic hydrogen peroxide on N,N -diarylthioureas (in the absence of acids) have proved to be merely the corresponding IV.IV -diarylureas.88... 

N. R. Phase transfer catalyzed N-alkylation of sym-N,N -diarylureas. Organic Preparations and Procedures International 1992, 24, 83-87. 

The low reaction rates usually associated with the MBH reaction can be increased either by pressure [15a, 22, 34], by the use of ultrasound [35] and micro-wave radiation [14a], or by the addition of co-catalysts. Various intra- or inter-molecular Lewis acid co-catalysts have been tested [26, 36, 37] in particular, mild Bronsted acids such as methanol [36, 57d], formamide [38], diarylureas and thioureas [39] and water [27a, 40] were examined and found to provide an additional acceleration of the MBH reaction rate (Table 5.1). 

In these four classes, our interest was directed at the diarylurea scaffold because there were five potent compounds with a diarylurea stmcture, which is appropriate for the rapid construction of structurally diverse libraries. Therefore, we constructed diarylurea informer libraries by parallel synthesis to validate the potential of the scaffold and to obtain preliminary SAR. 

Based on the results of the docking study with the Cdk4 model. X-ray analysis of the Cdk2 complex, and the SAR obtained by the Cdk4 inhibitory assays, we concluded that mode A was the most preferable binding mode of the diarylurea series of lead compounds in the activated form of the cyclin D-Cdk4 complex. 

NJSf -Disubstituted ureas 39 can be dehydrated with phosphorous pentoxide to give carbodiimides in good yields. For example, refluxing of 1,3-dicyclohexylurea and phosphorous pentoxide (live-fold excess) in pyridine affords DCC in 76 % yield. 1,3-diarylureas afford yields of 53-86 % under the same conditions. 

Etter, M. C., Urbanczyk-Lipkowska, Z., Zia-Ebrahimi, M. and Panunto, T. W. (1990ft). Hydrogen bond-directed cocrystallization and molecular recognition properties of diarylureas. / Am. Chem. Soc., 112, 8415-26. [55, 56,77]... 

Syntheses of N-arylurethanes and N,N -diarylureas for an approach to phosgene-free isocyanates could be accomplished by ruthenium complex-catalyzed dehydro-genative reactions of N-arylformamides, which are prepared by the carbonylation of aminoarenes (see Eq. 11.8), with alcohols [106] and aminoarenes [107], respectively. 

---