Pyrimidines arylation

There are few reports on the reactivity of aryl substituents attached to pyrimidine or quinazoline. However, nitration may be carried out with some success. 

The preparation of benzo fused pyrido[3,2- i]pyrimidines has furnished the only examples of the classic reaction of this type, the Bischler-Napieralski, involving the cyclization of 5-aryl-4-acylaminopyrimidines to 6-alkylpyrimido[4,5-c]isoquinolines, e.g. (157)->(158) (73YZ330). As often found in this reaction, the presence of activating substituents appears necessary (78CPB245). 

Aromatic aldehydes give 2-aryl-4-oxo derivatives (181) in the presence of concentrated sulfuric acid (70EGP73039), whilst pyrimidine derivatives (182) give octahydropyrido[4,3-with formaldehyde (e.g. 66M52). A similar reaction is observed with 6-methylpyrimidinones (e.g. 70M1415). 

Pyrimido[4,5-d]pyrimidine, 3-aryl-1,2,3,4-tetrahydro- H NMR, 3, 338 (69JOC2760) Pyrimido[4,5-d]pyrimidine, 4-hydroxy-UV, 3, 338 (58JOC1451) Pyrimido[4,5-d]pyrimidine, 4-hydroxy-2-methyl-7-(methylmercapto)-UV, 3, 338 (60JA5711)... 

Pyrimidine, I-alkyl-2-methyltetrahydro-C-thioacylation, 4, 807 Pyrimidine, 4-alkylsulfinyl-nucleophilie displaeement reaetions, 3, 97 Pyrimidine, 6-alkylsulfinyl-nucleophilic displacement reactions, 3, 97 Pyrimidine, 2-alkylsulfonyl-nueleophilie displaeement reactions, 3, 97 Pyrimidine, 4-alkylsulfonyl-nucleophilic displacement reactions, 3, 97 Pyrimidine, 6-alkylsulfonyl-nucleophilie displaeement reactions, 3, 97 Pyrimidine, alkylthio-dealkylation, 3, 95 desulfurization, 3, 95 oxidation, 3, 96 synthesis, 3, 135, 136 Pyrimidine, 2-alkylthio-aminolysis, 3, 96 hydrolysis, 3, 95 Prineipal Synthesis, 3, 136 Pyrimidine, 4-alkylthio-aminolysis, 3, 96 hydrolysis, 3, 95 Pyrimidine, 6-alkylthio-aminolysis, 3, 96 hydrolysis, 3, 95 Pyrimidine, 4-allenyloxy-rearrangement, 3, 93 Pyrimidine, 4-allyloxy-2-phenyl-rearrangement, 3, 93 Pyrimidine, 4-allynyloxy-rearrangement, 3, 93 Pyrimidine, 4-anilino-2,5,6-trifluoro-NMR, 3, 63 Pyrimidine, 2-aryl-pyrroleaeetic aeid from, 4, 152 Pyrimidine, arylazo-synthesis, 3, 131 Pyrimidine, 4-arylazo-reduetion, 3, 88... 

Thieno[2,3-d ]pyrimidin-4(3 H) -one, 3-methyl-synthesis, 4, 1017 Thieno[2,3-d ]pyrimidin-4-ones synthesis, 4, 1017, 1018, 1022 Thieno[2,3-6]pyrrole, 5-aryl-synthesis, 6, 1009 Thieno[2,3-6]pyrrole, N-benzyl- H NMR, 4, 1042 UV spectra, 4, 1044 Thieno[2,3-c]pyrrole, N-ethyl-UV spectra, 4, 1044 Thieno[3,2-6]pyrrole, 5-aryl-synthesis, 6, 1009 Thieno[3,2-6]pyrrole, N-benzyl- H NMR, 4, 1041, 1042 lithiation, 4, 1051 UV spectra, 4, 1044 Thieno[3,2-6]pyrrole, 2,3-dihydro-desulfurization, 6, 984 oxidation, 6, 981... 

Instead of perchlorates, tnfluoromethanesulfonates (Inflates) can be used They are readily prepared and claimed to be safer than perchlorates [75] F Aryl fluondes have been prepared from p YC6H4N" (CH3)3CF3S03- (Y = COCqHs, CN, CHO, NO2, COCH3, CO2C2H5) by this alternative substrate Fluorodequaternization can also be applied to the preparation of fluonnated heterocyclics such as 4 fluoro 6 phenyl 1,3 pyrimidine [76] (equation 15) and fluoropunnes [77]... 

A. Quinazolines Substituted in the Pyrimidine Ring 1. Alkyl- and Aryl-quinazolines... 

The use of substituted 2-aminonicotinio acids has enabled a series of pyrido[2,3-d]pyrimidines, which have 5-, 6-, and 7-alkyl and aryl substituents, to be obtained. 

The reaction involves an electrophilic attack into the 5-position of the pyrimidine ring and thus only those pyrimidines that are activated toward electrophilic substitution by the presence of electron-donating substituents at the 2- and 4-positions undergo cyclization. 2,4,6-Triaminopyrimidine, 6-aminouracil, 6-amino-2-thiouracil, 4-amino-2,4 dimercaptopyrimidine, 2,4-diaminopyrimidin-6(l/I)-one, and various 4-amino-vV-alkyl and aryl pyriinidones have all been converted into pyrido[2,3-[Pg.160]

V. Acyl acetates. j8-Keto esters have proved useful for the preparation of pyrido[2,3-d]pyrimidin-7(8H)-ones bearing alkyl and aryl... 

Reactions of iV -alkylated or arylated azinium compounds with nucleophiles proceed more readily than those of the parent, uncation-ized azines, and the ring tends to open. The iV -substituent may bring into play an accelerative effect from the London forces of attraction. Increased displaceability of the substituent in iV -alkyl-azinium compounds has been noted for 2-halopyridinium (87) 1-haloisoquinolinium, 4-halopyrimidinium, 4-methoxypyrid-inium (88), 4-phenoxy- and 4-acetamido-quinazolinium (89), 3-methylthiopyridazinium, and 2-car boxymethylthiopyrimidi-nium salts (90). The latter was prepared in situ from the iV -alkyl-pyrimidine-2-thione. The activation can be effectively transmitted to... 

Cyclization of the 5-(A -arylcarboxamido)-4-hydrazino-6methylpyrim-idin-2-ones 104 with two molar equivalents of formaldehyde in the presence of pyridine caused the concomittant triazole and pyrimidine ring formation to yield the 4-aryl-l,3,4,10-tetrahydro-6-methyl-l,2,4-tria-zolo-[2,3,4-c,d]pyrimido[4,5-d]pyrimidine-5,8-diones 105 (89AP599)... 

Cyclization of A -aryl-2-(ethoxycarbonyl)-3-(2-pyridylamino)acrylamides 307 in AcOH, and in PPA, or in ethylene glycol afforded A-aryl-4-oxo-4//-pyrido[l,2-n]pyrimidine-3-carboxylic amide 308 (94KGS629, 95KFZ(5)39). 

Reaction of 2-(arylmethyleneamino)pyridines 335 and styrenes in the presence of hydroquinone afforded 2,4-diaryl-3,4-dihydro-2/f-pyrido[l,2-n]pyrimidines 336 by means of an inverse electron demand Diels-Alder reaction (95MI10). Reaction of 2-(benzylideneamino)pyridines 337 and chloroacetyl chloride gave 2-aryl-4//-pyrido[l,2-n]pyrimidin-4-ones 338 (97JMC2266). 

Cyclocondensation of 2-iminopiperidine and 3-aryl-2-propynylnitriles in THE or 5% MeCN/THF afforded 4-aryl-2-imino-6,7,8,9-tetrahydro-2H- and 2-aryl-4-imino-6,7,8,9-terahydro-4//-pyrido[l,2-n]pyrimidines in 70-98% and 2-30% yields, respectively (00OL3389). When the reactions were carried out in the presence of 2 equiv of NaHMDS the product ratio was reversed. 

Semiempirical PM 3 MO calculations were performed on eight 4-aryl-2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidin-l,3-diones and on their dimers (00JPO213). In all of the calculated structures the aromatic ring is almost perpendicular to the plane of the pyrido[l,2-c]pyrimidin-l,3-dione fragment, which is in accordance with the X-ray data for 4-(4-methylphenyl) derivative. 

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