A- pyrimidinium salts

SeienazOlo[3.2-a]pyrimidinium salts (Scheme 53) can be obtained by condensation of 2-araino-4-phenylselenazoles with an excess of /S-diketone of the type. R,COCHR COR. ... 

A microwave-assisted, one-pot, two-step protocol was developed for the construction of polysubstituted 2-aminoimidazoles 101 via the sequential formation of imidazo[l,2-a]pyrimidinium salts from readily available 2-aminopyrimidines 99 and a-bromocarbonyl compounds 100, followed by opening of the pyrimidine ring with hydrazine <06OL5781>. A... 

Synthesis A also may lead to N-substituted TPs. 4-Alkyl-ATs and 5-alkylamino-1,2,4-triazoles are cyclized by 3-ketocarboxylic esters (and equivalents) forming 3- and 4-alky 1-oxo-TPs, respectively [67JCS(C)503 70GEP1946315 87T2497]. Similar reactions with 1,3-diketones afford the following 1,3,4-triazolo[ 1,5-a]pyrimidinium salts 3-methyl (74KGS565),... 

Hu et al. (91MI1) report the Dimroth rearrangement of 2-hydrazino- to 2,3-diamino quinazolin-4-ones under catalysis of carboxylic acid derivatives this reaction is followed by an in situ cyclization in which the same carboxylic acid derivatives serve as C,-synthons. l-Acylamino-2-alkylthiopyrimidines are hydrazinolyzed and cyclized to 3-amino-1,2,4-triazolofl, 5-a]pyrimidinium salts (89EGP270711). 

Cyclization of l-(acylamino)pyrimidine hydroiodides (1) with alkyl ammonium acetates gave 3//J5//-l,2,4-triazolo[l,5-a]pyrimidines (2) (87 EGP246999 89ZC378). Condensation of the l-(acylamino)pyrimidinium salt 3 with hydrazine hydrate gave 4, which upon cyclization with acetic acid in the presence of perchloric acid afforded the 3-amino-l,2,4-triazolo [l,5-a]pyrimidinium salt 5 (89EGP270711) (Scheme 2). 

The 8-substituted l,2,4-triazolo[4,3-a]pyrimidinium salts (382) were prepared from pyrimidinium salts (380) with hydrazines (381) in boiling propanol followed by treating the mixture with acid (81EGP147944) (Scheme 72). 

Pyrido[l,2-n]pyrimidinium salts (6), which are of aromatic character, are easily formed from 2-aminopyridines and 1,3-dioxo compounds2 5 or the acetal and ketal equivalents of the latter,4 10 in acidic media (perchloric acid and concentrated hydrobromic acid). The acidic conditions may also be provided by using the salts (hydroperchlorate and hydroiodide) of the 2-aminopyridines.2 4 When the reaction is conducted in the absence of acid, the intermediate enamine (5) can be isolated.5-6 The reaction of fi-oxo acetals and 2-aminopyridines unsubstituted in position 6 leads to 4-substituted pyrido[l,2-a] pyrimidinium salts (6 R1 = H),5 7 whereas the 6-substituted 2-aminopyridines give rise to 2-substituted pyrido[l,2-a]pyrimidinium salts (6 R2 = H).5... 

Reaction of 1,3-diketones and 2-aminopyridines led to 2,4-disubstituted pyrido[l,2-a]pyrimidinium salts (6 R1 and R2 H), but the 6-substituted 2-aminopyridine failed to provide the bicyclic product.4,5 The irregular behavior of the 6-substituted 2-aminopyridines is explained by the steric hindrance effect of the 6-substituent. 

Sawyer and Wibberley5 demonstrated that the product obtained by Singh et al.i2 in the reaction of 2-amino-4-methylpyridine and acetylacetone in polyphosphoric acid was not the naphthyridine but was instead the enamine of type 5, which was formed by hydrolysis of the pyrido[l,2-a]pyrimidinium salt (6) when the reaction mixture was neutralized. Formation of both isomeric pyrido[l,2-c<]pyrimidinium salts with asymmetric 1,3-diketones (R1 R2) was occasionally observed.3... 

Pyrido[l,2-a]pyrimidinium salts were obtained as products when 1,2-diaminopyridinium iodide2 was used instead of 2-aminopyridine, and triacylmethanes4 instead of 1,3-diketones. In the latter case ring closure was... 

Reactions of 2-aminopyridines with /i-chlorovinyl ketones were surveyed by Fischer.16 He established that in a nonacidic medium (acetone-methanol mixture) the pyridinium salts (7) are formed, which can then be cyclized by acids (acetic acid and 70% perchloric acid) to the 2-substituted pyrido[l,2- ]-pyrimidinium salts (10).1415 in acidic media, however, the 4-substituted pyrido[l,2-a]pyrimidinium salts (9) are formed via the enamine (8).616... 

By the reaction of 2-(alkylamino or benzylamino)pyridines with epichlorohydrin or l,3-dichloro-2-propanol, quaternary pyrido[l,2-a]pyrimidinium salts (132) were obtained.188... 

In spite of their aromatic character, the pyrido[ 1,2-a]pyrimidinium salts are readily converted by alkalis to the enamines (5). Under acidic conditions the enamines (5) easily revert to the pyrido [l,2-a]pyrimidinium salts.5,6,9 The pyrido[l,2-a]pyrimidinium salts do not suffer hydrolysis upon heating in hydrochloric acid.3... 

On treatment of a solution of the pyrido[l,2-a]pyrimidinium salt (16) with potassium permanganate in 2 N sulfuric acid, 11% 2-aminopyridine, 1% 4-oxo-4H-pyrido[l,2-a]pyrimidine, and traces of 2-nitropyridine were isolated from the reaction mixture.9 When 2,4-dimethylpyrido[l,2-a]-pyrimidinium iodide was oxidized with aqueous potassium permanganate at 50-60°C, 2-acetamidopyridine was obtained in 65% yield.2... 

Methyl groups at positions 2 and/or 4 of the pyrido[l,2-a]pyrimidinium salts may be condensed with p-dimethyl-aminobenzaldehyde in acetic anhydride.3,4,13... 

Attempts to reduce the quaternary salts of 4-oxo-4//-pyrido[l,2-a]-pyrimidines with sodium borohydride or lithium aluminum hydride remained unsuccessful.137 At the same time the 6,7,8,9-tetrahydro quaternary salts may readily be reduced with sodium borohydride to the 1-alkyl-l,6,7,8,9,9a-hexahydro derivatives.75-77,133 1481269 270 Sodium borohydride reduction of the 1,6- and l,7-dimethyl-3-carbamoyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[l,2-a]pyrimidinium salts proceeds stereoselectively and yields the thermodynamically controlled product.271 The l-methyl-3-carbamoyl-4-oxo-l,6,7,8,9,9a-hexahydropyrido[l,2-a]pyrimidines were also prepared by the catalytic (Pd/C) hydrogenation of the 1,6,7,8-tetrahydro derivatives,270-272 but this reaction led to a diastereoisomeric mixture.271... 

The 3-ester group of quaternary pyrido[l,2-a]pyrimidinium salts was hydrolyzed under acidic conditions137,257 (see also Section lll,C,l). 

The 2- and 4-substituted pyrido[l,2-a]pyrimidinium salts may be distinguished by H-NMR spectroscopy. In the 2-substituted derivatives the coupling constant J = 6.9-7.6 Hz, whereas in the 4-substituted com-... 

Pyrido[l,2-a]pyrimidinium salts 286 easily suffered hydrolytic ring opening in basic media to give 3-(2-pyridylamino)acroleines 287 (86EUP174832). 

Diorganotin(IV) complexes (109) were prepared from 4//-pyrido[l,2-a]pyrimidin-4-ones with Me2SnCl2 and Ph2SnCl2 in dry CHC13 (96MI4). Different complexes of 2-methyl-9-hydroxy-4//-pyrido[l,2-<2]pyrimidin-4-one and its 8-nitro derivative were prepared with Cu(I)Cl, Cu(II)Cl2, Ni(H)Cl2, Co(II)Cl2, Mn(II)Cl2, and Ag(I)N03 in EtOH (00MI23). Complexes of 2,4-dimethyl-9-hydroxypyrido[l, 2-a]pyrimidinium salt were obtained with Pr(III), Nd(III), Sm(III), and Eu(III) ions in acetone (00MI24). 

Azole approach. Condensation of 2-aminooxazoles with 1,3-dicarbonyl compounds or /3-halo a,/3-unsaturated carbonyl compounds yields oxazolo[3,2-a]pyrimidinium salts (221). 2-Aminobenzoxazoles in the same way yield benzo homologues (74UKZ633). 

Condensations of 1,3-dicarbonyl synthons (99JCS(P1)1527) or equivalents (e.g., 33 or 34b) (99CHE708) and 4-substituted ATs provide an approach to quaternary 1,2,4-triazolo[l,5-a]pyrimidinium salts substituted onto N-3, such as 32 and 35 (Scheme 10). 

Certain types of pyrido[l,2-a]pyrimidines have aroused much interest owing to their valuable pharmacological properties. They are also used as synthetic intermediates or as additives to photographic materials and dyes. In the following sections the syntheses, reactions, physicochemical properties, and briefly the utilization of the pyrido[l,2-a]pyrimidines are discussed. Within the individual sections the pyrido[l,2-a]pyrimidinium salts, followed by the 2-oxo-2//-pyrido[l,2- ]pyrimidines, 4-oxo-4H-pyrido[l,2-a]pyrimidines, 3,4-dihydro-2W-pyrido[l,2-a]pyrimidines, 2-oxo-3,4-dihydro-2//-and 4-oxo-2,3-dihydro-4H-pyrido[l,2-a]pyrimidines, and finally miscellaneous pyrido[l,2-fl]pyrimidines are dealt with. 

Pyrido[l,2-a]pyrimidinium salts (6), which are of aromatic character, are easily formed from 2-aminopyridines and 1,3-dioxo compounds " or the acetal and ketal equivalents of the latter, " in acidic media (perchloric acid and concentrated hydrobromic acid). The acidic conditions may also be provided by using the salts (hydroperchlorate and hydroiodide) of the... 

The reaction of j8-oxo acetals and 2-aminopyridines unsubstituted in position 6 leads to 4-substituted pyrido[l,2-u] pyrimidinium salts (6 R = H), whereas the 6-substituted 2-aminopyridines give rise to 2-substituted pyrido[l,2-a]pyrimidinium salts (6 = H). ... 

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