4.5- disubstituted pyrimidine derivatives

A ZnCh-catalyzed, three-component coupling reaction involving a variety of functionalized enamines, triethyl orthoformate, and ammonium acetate, leads to the production of 4,5-disubstituted pyrimidine derivatives in a single step. This type of [3+1+1+1] aimulation process has not previously... 

Amino-4//-pyrido[],2-rz]pyrimidin-4-ones 184 were obtained from 3-(2,2-disubstituted ethenylamino) derivatives 183 with H2NNH2 H2O or HONH2 HCI m good yields, and from 183 (R = COOCH2Ph, R = acetyl) by treatment with NaBH4 in moderate yields (97H(45)2349,... 

The tetrahydropyridopyrimidine 394 was obtained via condensation of 5-acetyl-4-arylamino-6-methyl-2-styrylpyr-imidine with benzaldehyde <1997PJC1232>. The 5,8-dihydropyrido[2,3 Pyrimidine derivatives 395 could be obtained from condensing 5-acetyW-amino-2,6-disubstituted pyrimidines with ethyl oxalate in the presence of alkoxide by-products of Friedlander self-condensation of 395 were also obtained <2002RCB1875>. 

Pyrimidine derivatives are frequently used as functional materials or are found in their partial structures. A great number of methods for construction of pyrimidine skeleton have been reported in which the majority is the condensation of a C - C - C unit (e.g., malonaldehyde, malononitrile, diethyl malonate) and an N-C-N unit (e.g., urea, guanidine) [46]. On the other hand, the general method involving a combination ofC-N-C, C-C and N units is not known to our best of knowledge. Thus, the present TCRT will be an alternative method for the preparation of 4,5-disubstituted pyrimidines, however, this reaction suffers from limited scope of ketones. When cyclohexanone is employed, tetrahydroquinazoline 26d is effectively formed... 

Many studies on the spectroscopic properties in the near and far ultraviolet region of cytosine, uracil, thymine, their derivatives, nucleotides and nucleosides have been made in recent years. DeVoe and Tinoco, for instance, following previous efforts by other investigators, have extended to short wavelengths ( 186 nm) the measurements of the absorption spectra of the four deoxyribonucleo-sides of DNA. Marshall and Walker have analyzed the UV spectra of 2,4-disubstituted pyrimidines, and Shugar and Fox ° examined the spectra of the p3n imidine bases of the nucleic acids and their... 

ACSA(B)62]. The stannanes are available from enol ethers by a-lithiation and quenching with trialkylstannyl chloride. The coupling reactions have been run on derivatives that had either a chlorine atom in an activated position or a bromine atom in the benzenoid position. Mild acid hydrolysis of the a-pyrimidinylalkenyl ethers yields ketones, the acyl-substituted pyrimidines. In the 4,5-dichloro derivative (130), the masked acyl group is introduced into the electrophilic 4-position (131). In the 2,5-disubstituted pyrimidine (133), having a methyl group in the 5-position and a chlorine atom in the 2-position results in the addition of a masked acyl group in the electrophilic 2-position (134). When the 5-substituent in the latter example is a bromine atom, the chemoselectivity leads to masked acylation in 5-position (135). This reaction sequence constitutes a convenient... 

The Af-cyano example is from the reaction between Af-cyano-5-methylisothiourea and cyclohexanone, which forms 2-methylthio-5,6,7,8-tetrahydro-4-quinazolinamine (548). Acyclic ketones yield the corresponding 5,6-disubstituted pyrimidines but in inferior yields, for example, the 5-methyl-6-ethyl derivative from diethyl ketone <81CPB948,93AHC(57)1>. 

Thiazolidines incorporating a hydroxyamine function (258) are formed directly by the condensation of iV-hydroxythioureas (257) and chloroacetyl chloride. They are isomerized to the 3-aryl-2-hydroxyiminothiazolidin-4-ones (259) by methanolic sodium methoxide. 2,3-Disubstituted thiazolidin-4-ones of type (261) are accessible by the condensation of the appropriate thioamides (260) with bromoacetic ester. l-Acyl-1,3,3-trichloroprop-2-enes (263), showing the usual reactivity of a-chloroketones, react with thiourea to yield 4-substituted 2-amino-5-(2, 2 -dichlorovinyl)-4-hydroxythiazolidines (262). The pyrimidine derivative (264), bearing three thiazolidine nuclei, is formed from trithiobarbituric acid by an application of this synthesis. ... 

Herbicidally active sulfonylurea derivatives with other heterocyclic systems (Figure 7) were prepared but these compounds were less active than the 4,6-disubstituted pyrimidines and 4,6-disubstituted 1,3,5-triazines. 

As was shown earlier, sulfonylureas are derived from a sulfonamide, a phosgene equivalent in some form, and a heterocyclic amine. Of these amines, the simple disubstituted pyrimidines and symmetrical triazines generally afford the most active herbicides. The following discussion will highlight tiie synthesis of a variety of different heterocyclic amines that have been incorporate into sulfonylureas to define the limits of herbicidal activity, and to (tiscover active herbicides with high crop selectivity. 

Apart from the two disubstituted compounds mentioned above, veiy few disubstituted pyrimidines appear to have been quatemized. The 4,6-dimethyl derivative, which can give only one mono-salt, reacts easily with methyl iodide. Although the quaternization of 2,4-dimethylthiopyrimidine gives salts of unspecified structure, they have been used en route to the cyanine dyes presumably reaction occurs at N-1. Treatment of 2,4-dimethoxypyrimidine with methyl... 

Tetrahydroquinazolines are more conveniently classified as 4,5-tetramethylene pyrimidines and their reactions are accordingly typical of pyrimidines. 2,4-Disubstituted derivatives have been prepared by condensation of 1-ethoxycarbonyl cyclohexanones with ureas and thioureas (Scheme 9). For monosubstituted derivatives the... 

---