4- tetrahydropyrimidines

Pyrantel and its methyl analogue, morantel, constitute the group of the tetrahydropyrimidine anthelminthics currently used in food-producing animals. Both 

In all species, morantel is mostly unabsorbed and excreted in the feces. Only a small proportion of the administered dose is rapidly absorbed, producing peak blood levels within 4-6 h. The drug is quickly metabolized, presumably in the liver, and 17% of the administered dose is excreted in the urine of sheep in the form of metabolites within 4 days after administration (1). In cattle, less than 20% of the administered dose is recovered in the urine over 4 days after administration, whereas in swine 45% of the administered dose is excreted in urine within 24 h. 

Due to the extensive metabolism of morantel in vivo, total morantel-related residues in edible animal products are usually determined after their conversion to either A-methyl-l,3-propanediamine through alkaline hydrolysis or to 3-(3-methyl-2-thienyl (acrylic acid through digestion with hydrochloric acid. 

When calves were given orally a single dose of 5.9 mg radiolabeled mor-antel tartrate/kg bw, kidney contained 60 ppb, fat 20 ppb, and muscle less than 10 ppb of morantel equivalents at 7 days after dosing. In liver, the amounts of radioactivity were 495, 250, and 140 ppb morantel equivalents at 1, 14, and 28 day after dosing, respectively. Following conversion of residues to Al-methyl-1,3-propanediamine, the proportion of this compound in total residues in liver was found to be 59%, 54%, and 40% at 1,14, and 28 day after dosing, respectively. 

When ruminating calves were given an intraruminal bolus containing 12 g morantel, the concentrations of morantel residues, after their conversion into 3-(3-methyl-2-thienyl)acrylic acid, in muscle, kidney, and liver, were 15, 40, and 150 ppb morantel equivalents, respectively, at 7 days after dosing. 

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Use of 1,3 cycloaHphatic diamines in polyamides may be similarly limited by internal amide dehydration of the conformationaHy labile cis isomers to form a tetrahydropyrimidine (38) rather than high molecular weight polyamide. 1,3-Cyclohexanediamine is, however, a component of Spandex polyureas Du Pont uses the hydrogenation product of y -phenylenediamine [108-45-2] (24) captively to produce Lycra (see Fibers, elastomeric). 

Orotic acid (2,6-dioxo-l,2,3,6-tetrahydropyrimidine-4-carboxylic acid)... 

Lithiation of 2-(2-alkylphenyl)-l,2,3,4-tetrahydropyrimidines 427 with 1.3 M BuLi in the presence of A/, A/, A, A -tetramethylethylenediamine, then with 1.3 M -BuLi, followed by the addition of a carboxylic acid methyl ester, and treatment of the reaction mixture with pTSA afforded 3,4-dihydro-2/f-pyrimido[2,l-u]isoquinolines 428 after chromatographic work-up (98JMC1050). 

Annular tautomerism in tetrahydropyrimidines has also been studied for a few N-unsubstituted tetrahydropyrimidines bearing OH groups at the 6 position. X-Ray analysis of bicyclic 58 (R = H) revealed that its crystals are composed of two independent tautomeric molecules, 58a and 58b (Scheme 24), connected by three hydrogen bonds (86JHC705). According to NMR spectroscopy, the same tautomers 58a/58b (R = H, Me) coexist in solution, their ratios being dependent on the solvent polarity. 

However, another representative of benzo-fused tetrahydropyrimidines, 3,4,5,6-tetrahydrobenzo[/i]quinazoline 61, was reported to exist exclusively as the tautomer shown, without any indication of the annular tautomeric equilibrium (91M209). 

C for two hours, it was acidified at this temperature by the addition of ethanolic hydrogen chloride. The mixture was warmed to room temperature and filtered to remove 4.3 grams of solid ammonium chloride. The filtrate was concentrated to approximately 40 ml, filtered and refrigerated. The solid which separated was isolated, washed with acetone and dried. There was obtained 7.4 grams (40% of the theoretical yield) of 2-chloromethyl-4-methyl-1,4,5,6-tetrahydropyrimidine hydrochloride melting at 158° to 160°C. 

A solution of 0.1 mol of each of thiophene-2-carboxaldehyde and 1,2-dimethyl-1,4,5,6-tetrahydropyrimidine in dimethyl carbonate (0.2 mol) is held at 27°C for 48 hours. The reaction mixture is then stripped to give a 65% yield of product as the free base. 

Fig. 3-12. Selectivity factors for the separations of sublibraries of racemic ethyl (6-methyl-) and (ethyl 1,6-dimethyl) 2-oxo-4-substituted-l,2,3,4-tetrahydropyrimidine-5-carboxylates. (Reprinted with permission from ref. [55]. Copyright 1999, American Chemical Society.)...

Preparation of 2-thioxo Tetrahydropyrimidin-4-(1H)-ones on Ionic Liquid Support... 

Bazureau et al. have reported a similar protocol to that described in Sect. 8.1 for the rapid synthesis of 2-thioxo tetrahydropyrimidin-4-(lH)-ones via cycli-zation of a primary amine with an isothiocyanate and a /1-dielectrophile (Fig. 35) [138]. First a j6-amino ester was linked to the ionic hquid support... 

Fig. 35 Preparation of 2-thioxo tetrahydropyrimidin-4-(2H)-ones on ionic hquid support. Reagents and conditions a R N = C = S, MeCN, rt, 18 h b Et2NH, MW, 120 °C, 15-45 min. R = Pr, i-PrCH2, PhCH2 R = Me, Bu...

C1H5CIO 107-30-2) see Cefoxitin Troglitazone 3 (chloromethyl) l melhylplperidine methyMA5,6-tetrahydropyrimidine (QHi,CIN2) see Oxyphencyclimine... 

Fig. 4.15), are active for ATRP of both styrene and methylmethacrylate (MMA) [46]. Polymerisation was well controlled with polydispersities ranging from 1.05 to 1.47. The rates of polymerisation 1 x 10 s ) showed the complexes to be more active than phosphine and amine ligated Fe complexes, and were said to rival Cu-based ATRP systems. It was quite recent that Cu(I) complexes of NHCs were tested as ATRP catalysts [47]. In this work, tetrahydropyrimidine-based carbenes were employed to yield mono-carbene and di-carbene complexes 42 and 43 (Fig. 4.15), which were tested for MMA polymerisation. The mono-carbene complex 42 gave relatively high polydispersities (1.4-1.8) and a low initiation efficiency (0.5), both indicative of poor catalyst control. The di-carbene complex 43 led to nncontrolled radical polymerisation, which was ascribed to the insolubility of the complex. 

Ligand abbreviations (6-Mepy)(py)2tren and (6-Mepy)2(py)tren = tris[4-[(6-/ )-2-pyridyl]-3-aza-6-butenyl]amme, R = H or CH3 HB(pz)3 = hydro-tris(pyrazolyl)borate paptH = 2-(2-pyridylamino)-4-(2-pyridyl)thiazole phenmethoxa = 3-[2-(l,10-phenanthrolyl)]-5-methyl-l,2,4-oxadiazole pyimH = 2-(2 -pyridyl)itnidazole pybimH = 2-(2 -pyridyl)benzimidazole ppa = JV -(2-pyridylmethyl)picolineamidine tpmbn = tetrakis(2-pyridylmcthyl)-meso-2,3-butane-diamine tppn = tetrakis-(2-pyridylmethyl)-l-methyl-l,2-propanediainine tpchxn = tetrakis(2-pyridylmethyl)-tra s-l,2-cyclohexanediamine biz = 2,2 -bi-1,4,5,6-tetrahydropyrimidine. 

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