Disubstituted pyridine/pyrimidine

Disubstituted pyridine/pyrimidine ferrocenyl complexes have been obtained by mechanically (mortar and pestle) induced Sukuzi coupling reactions in the solid state. The solventless process is much faster, and more selective, than the same reaction carried out in solution (040RM2810). The synthesis and structure of the complex [Fe(ri -C5H4-4-C5H4N)(Ti -C5H4-3-C4H3N2)] are reported as a test case. 

Substituted pyrimidine N-oxides such as 891 are converted analogously into their corresponding 4-substituted 2-cyano pyrimidines 892 and 4-substituted 6-cya-no pyrimidines 893 [18]. Likewise 2,4-substituted pyrimidine N-oxides 894 afford the 2,4-substituted 6-cyano pyrimidines 895 whereas the 2,6-dimethylpyrimidine-N-oxide 896 gives the 2,6-dimethyl-4-cyanopyrimidine 897 [18, 19] (Scheme 7.6). The 4,5-disubstituted pyridine N-oxides 898 are converted into 2-cyano-4,5-disubsti-tuted pyrimidines 899 and 4,5-disubstituted-6-cyano pyrimidines 900 [19] (Scheme 7.6). Whereas with most of the 4,5-substituents in 898 the 6-cyano pyrimidines 900 are formed nearly exclusively, combination of a 4-methoxy substituent with a 5-methoxy, 5-phenyl, 5-methyl, or 5-halo substituent gives rise to the exclusive formation of the 2-cyanopyrimidines 899 [19] (Scheme 7.6). The chemistry of pyrimidine N-oxides has been reviewed [20]. In the pyrazine series, 3-aminopyrazine N-ox-ide 901 affords, with TCS 14, NaCN, and triethylamine in DMF, 3-amino-2-cyano-pyrazine 902 in 80% yield and 5% amidine 903 [21, 22] which is apparently formed by reaction of the amino group in 902 with DMF in the presence of TCS 14 [23] (Scheme 7.7) (cf. also Section 4.2.2). Other 3-substituted pyrazine N-oxides react with 18 under a variety of conditions, e.g. in the presence of ZnBr2 [22]. 

Calamitic compounds which exhibit a smectic and/or nematic phase usually consist of a relatively rigid central core containing co-linear six-membered rings, either aromatic rings, such as 1,4-disubstituted-phenylene, 2,5-disubstituted-pyridine, 2,5-disubstituted-pyrimidine, 3,6-disubstituted-pyridazine, and alicyc-lic rings, such as /ra j-l,4-disubstituted-cyclohexane, 1,4-disubstituted-bicy-clo[2.2.2]octane, 2,5-disubstituted-dioxane. Heteroaromatic rings tend to lead to the formation of smectic phases rather than the nematic phase unless combined with a polar terminal function, such as a cyano group. The dependence of the liquid crystalline transition temperatures on the nature of... 

Potts s synthesis of 2,6-disubstituted pyridines was used by Lehn and coworkers to prepare alternating pyridine-pyrimidine oligomers (Scheme 9.9) [18], Potts s... 

Scheme 9.9 Potts s method for the synthesis of 2,6-disubstituted pyridines. Synthesis of oligopyridine-pyrimidines.

In coordination chemistry, architectures containing the triazole heterocycle have been developed as monodentate and polydentate nitrogen ligands. Special attention has been given to (2-pyridyl)- and more flexible (2-picolyl)-l,2,3-triazoles. Thus, a hbrary of selected 1,4-disubstituted 1,2,3-triazoles differently functionahzed with pyridine, pyrimidine, and pyrazine have been synthesized by the reaction of aryl, heteroaryl, and heteroarylmethyl azides with alkynes. Three different copper(l) sources, that is, CuSO /sodium ascorbate, CuBrlPPhglg, and (CuOTf)2 CgHg, were used to promote the reactions [89]. 

The syntheses of pyrido[3,2-d]pyrimidines from pyridines utilize a 2,3-disubstituted pjrridine and insert the C-2 and N-3 atoms, either previously linked (route i) or in separate stages (route ii). 

AJC287>. From a complex reaction mixture of BuCH(COCl)2 and 2- 4-[(4-hydroxy-3-carboxyphenyl)hydrazi-no]phenylsulfonylamino pyridine at elevated temperature, tf yr/r >-(3-butyl-2-hydroxy-4-oxo-4//-pyrido[l,2-tf]pyrimi-din-3-ylium)hydroxide was isolated <2001MI53>. Reaction of 2-aminopyridines and diethyl alkylidenemalonates at 175 °C yielded 3-(2,2-disubstituted vinyl)-2-hydroxy-4//-pyrido[l,2-tf]pyrimidin-4-ones from the initially formed... 

Pyridines and 4,5-disubstituted pyrimidines can be synthesized from 1,3,5-triazine with compounds containing a reactive methylene group (Schemes 11 and 12) (63AG. 

Aryl fluoroalkyl ethers have been prepared from the reaction, at room temperature in HMPA, of fluo-ro-substituted alkoxides with activated fluoro-,149 nitro-,149 and, at 150 °C, also chloro-arenes150,151 and some chloro-substituted pyrazines (equation 15), pyrimidines, quinolines,150,152 and pyridines.152 Disubstitution was observed in die presence of comparably activated leaving groups such as in 2,4- and 2,6-di-chloronitro- or cyano-benzenes, whereas regiospecific substitution took place at position 4 in 3,4-dichloronitro- or cyano-benzene and at position 2 in 2-fluoro-6-chlorocyanobenzene.151 Steric hindrance and the number of fluorine substituents in the alkoxide pose limits to the reactivity. Thus, tertiary alkoxides, or alkoxides containing more than four fluorine substituents, displace activated nitro and fluoro, but not chloro substituents.149,150 The secondary hexafluoro-2-propoxide anion does not react even with the more reactive nitro and fluoro derivatives.149... 

The reaction of 3-substituted triazolo[4,5- ]pyrimidines (8-azapurines) (213) with activated methylene synthons in the presence of sulfuric acid is reported to afford 5,6-disubstituted triazolo[4,5-i]pyridines (215). Since these reactions occur via 5-amino-4-formyltriazoles (214) (79CPB2861, 88BSCB85), similar cyclizations of other derivatives of 5-amino-4-formyltriazole have afforded additional analogues (Table 12) <73JCS(P1)1620>. Higashino and co-workers have also shown that 3//-triazolo[4,5- ]pyrimidines (213) participate in an inverse-electron Diels-Alder reaction with enamines (216) to afford the derivatives (215), albeit in low yields (Schemes 40 and 41) <91CPB282>. 

Condensation of 3-amino-4,6-disubstituted-l/7-pyrazolo[3,4-6]pyridines 628 with l,l,l-trifluoro-3-isobutoxymethylene-2-propenones 629 in xylene under MWI took 12-24min to afford pyrido[2, 3 3,4]pyrazolo[l,5-a]pyrimidines 630 in 62-82% yields (Scheme 123), higher than that obtained ( 20%) under conventional heating (97JFC127). 

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