6-Hydroxypyrimidine

Repeat your analysis for tautomeric equilibria between 4-hydroxypyridine and 4-pyridone, 2-hydroxypyrimidine and 2-pyrimidone and 4-hydroxypyrimidine and 4-pyrimidone. For each, identify the favored (lower-energy) tautomer, and then use equation (1) to calculate the ratio of tautomers present at equilibrium. Point out any major differences among the four systems and rationalize what you observe. (Hint Compare dipole moments and electrostatic potential maps of the two pyridones and the two pyrimidones. How are these related to molecular stability )... 

Hydroxypyrimidine (89a) can tautomerize to two alternative 0X0 forms, 90 (R = H) and 91 (R = H). The infrared solution spectra of pyrimidin-2- and -4-one clearly indicate the presence of both C=0 and NH groups, and by using these spectra Mason demonstrated that pyrimidin-4-one existed predominantly in the o-quinonoid... 

Shugar and FoxS " reported that 4-ethoxypyrimidin-2-one exists in the 0X0 form 102 since its ultraviolet spectrum is different from that of 103. They further claimed that the isomeric compound, 2-ethoxy-4-hydroxypyrimidine, existed in the hydroxy form (104) however, reexamination of the ultraviolet spectral data suggests that this unlikely conclusion may be incorrect, and the infrared spectrum of 104 does, indeed, show a carbonyl absorption band. 2-Methylthiopyrim-idin-4-one has been reported to exist in the hydroxy form, but this to appears unlikely. 

The monoimines of the substituted -diketones formed can usually be isolated but sometimes they undergo further reactions. Thus, 5-substituted 3-chloroisoxazoles yield / -ketonitriles, and hydrogenation of 5-acylaminoisoxazoles (174) is a general method of synthesizing 4-hydroxypyrimidines (175). 2 3,214 One should note the increased stability of the isoxazole ring in styrylisoxazoles toward reduction. No hydrogenolysis of the 0—N... 

Dowtherm A at 260-267°C for 6-60 min gave pyrido[3,2- /Jpyrimidine-7-carboxylates (592 and 594) in 66-91% yields [67JCS(C)1745, 67USP332-0257], but A/-(4-hydroxypyrimidin-5-yl)aminomethylenemalonate (595) failed to cyclize under similar conditions [67JCS(C)1745]. 

Ethyl 4-hydroxypyrimidine-5-carboxylate was obtained in 90% yield in the reaction of 1,3,5-triazine and diethyl malonate in the presence of diethylamine in ethanol for 14 days (77AP353). 

Hydroxypyrimidine and 4-hydroxypyrimidine, which exist predominantly as tautomers [135] and [136] (Gronowitz and Hoffman, 1960), become monoprotonated in trifluoroacetic acid on... 

Since a knowledge of the correct tautomeric form of the pyrimidines is a requisite for understanding the mode of binding to active sites, as well as nucleic acid structure and modification, the formulae of the conventionally-named 2- and 4-hydroxypyrimidines are presented in the correct lactam, or pyrimidone, form in this chapter. Other physical properties of the pyrimidines, such as dissociation constants, protonation sites, and distribution coefficients, are presented in cases where there is a known relation to drug activity. Biogenesis and enzyme control mechanisms are discussed where they relate to an understanding of inhibitor action. 

Hydroxy-1,2,4-thiadiazoles are generally distinctly acidic. 3-Ethyl-5-hydroxy-1,2,4-thiadiazole, for example, is more acidic than nitrophenol and 4-hydroxypyrimidine, but less so than 2,4-dinitrophenol. 3-Hydroxy-1,2,4-thiadiazoles fail to afford ketonic derivatives and give red to purple colors with iron(III) chloride, indicating their phenolic nature <65AHC(5)119>. Their IR spectra in... 

Both 2- and 4-hydroxypyrimidine can exist in both hydroxyl and keto tautomeric forms, and the proportion of each is highly dependent on the state of the molecule. In the gas phase 2-hydroxypyrimidine 20 exists primarily in the hydroxy form, whereas the 4-isomer 21 exists predominantly in the oxo form <2006AHC(91)1>. Solvation tends to shift the equilibrium toward the oxo form for both isomers <2006AHC(91)1>. 

In six types of soils, Somasundaram et al. (1991) reported that diazinon was hydrolyzed to 2-isopropyl-6-methyl-4-hydroxypyrimidine and that the degradation product was significantly more mobile in these soils than its parent compound diazinon. In an earlier study, Somasundaram et al. (1989) found that prior applications of 2-isopropyl-6-methyl-4-hydroxypyrimidine did not enhance degradation of diazinon. 

Methods for Determining Biomarkers of Exposure and Effect. Section 2.6.1 reported on biomarkers used to identify or quantify exposure to diazinon. Some methods for the detection of the parent compound in biological samples were described above. The parent chemical is quickly metabolized so the determination of metabolites can also serve as biomarkers of exposure. The most specific biomarkers will be those metabolites related to 2-isopropyl-6-methyl-4-hydroxypyrimidine. A method for this compound and 2-(r-hydroxy-l -methyl)-ethyl-6-methyl-4-hydroxypyrimidine in dog urine has been described by Lawrence and Iverson (1975) with reported sensitivities in the sub-ppm range. Other metabolites most commonly detected are 0,0-diethylphosphate and 0,0-diethylphosphorothioate, although these compounds are not specific for diazinon as they also arise from other diethylphosphates and phosphorothioates (Drevenkar et al. 1993 Kudzin et al. 1991 Mount 1984 Reid and Watts 1981 Vasilic et al. 1993). Another less specific marker of exposure is erythrocyte acetyl cholinesterase, an enzyme inhibited by insecticidal organophosphorus compounds (see Chapter 2). Methods for the diazinon-specific hydroxypyrimidines should be updated and validated for human samples. Rapid, simple, and specific methods should be sought to make assays readily available to the clinician. Studies that relate the exposure concentration of diazinon to the concentrations of these specific biomarkers in blood or urine would provide a basis for the interpretation of such biomarker data. 

There are also methods for the analysis of diazinon degradation products in air, water, and soil. Williams et al. (1987) published a method for diazinon and its oxon (diazoxon) in air. Other methods have been reported for diazinon, its oxon, and hydrolysis products in water (Suffet et al. 1967), soils and water (Lichenstein et al. 1968), and soil (Burkhard and Guth 1979). The hydrolysis product 2-isopropyl-6-methyl-4-hydroxypyrimidine was studied along with diazoxon in submerged soil (Sethunathan and Yoshida 1969). Suffet et al. (1967) demonstrated the ability of GC to separate diazinon, diazoxon, and 2-isopropyl-6-methyl-4-hydroxypyrimidine. However, no validated methods for the determination of... 

Hydroxypyrimidine [4562-27-0] M 96.1, m 164-165". Crystd from benzene or ethyl acetate. 

Extra nitrogen heteroatoms in the ring provide alternative sites for the tautomeric proton. 4-Hydroxypyrimidine, for instance, can exist as such (92), or in the 1H- (93) or 3H- (94) pyrimidone... 

The most important route is the conversion of pyrimidines into 1,3,5-triazines. The first one-step transformation was effected by Taylor and Jefford (62JA3744) by heating the pyrimidine (179) with benzenesulfonyl chloride in pyridine (equation 106). The reaction may be considered as an example of an abnormal Beckmann rearrangement. The mechanism of the reaction of the 4-aminopyrimidine (180) is probably dependent on the nature of the 2-substituent (180, R). If R is an electron-releasing moiety, pathway B seems more likely (Scheme 109). The 4-hydroxypyrimidine (179 R = OH) behaves similarly. Many 2-cyano-1,3,5-triazines may be synthesized by this method. 

Hydroxypyrimidine and exist instead in their keto forms. 

Reductive animation of 2-acetamido-5-amino-4-hydroxypyrimidine, readily available from isocytosine via nitration, acetylation and reduction, with (299) generated (300), which was characterized as the crystalline bisformamide (301). Mild acid hydrolysis effected cleavage of all three amide bonds to afford (302), which was hydrolyzed to (303) under slightly more vigorous conditions. 

Nitrogen-containing heterocycles are of obvious interest in the context of prebiotic chemistry. This is the reason why we will now consider this class of derivatives. The first so-called evidence for the presence of 4-hydroxypyrimidine and 4-hydroxy-methyl-pyrimidine in Murchison was published in 197158These results were divergent from those of previous studies performed on Orgueil samples where adenine, guanine, j-triazines and guanylurea were detected 59 60). 

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