Pyridine-3-carboxaldehyde condensation

Bisa.codyl, 4,4 -(2-PyridyLmethylene)bisphenol diacetate [603-50-9] (Dulcolax) (9) is a white to off-white crystalline powder ia which particles of 50 p.m dia predominate. It is very soluble ia water, freely soluble ia chloroform and alcohol, soluble ia methanol and ben2ene, and slightly soluble ia diethyl ether. Bisacodyl may be prepared from 2-pyridine-carboxaldehyde by condensation with phenol and the aid of a dehydrant such as sulfuric acid. The resulting 4,4 -(pyridyLmethylene)diphenol is esterified by treatment with acetic anhydride and anhydrous sodium acetate. Crystallisation is from ethanol. 

Gutman,50 in his process route, which did not report any yields, hydrogenated the pyridine ring first to access the piperidine moiety and constructed the indanone ring system via an intramolecular Friedel-Crafts acylation (Scheme 5). Hydrogenation of diester 31, obtained from condensation of 4-pyridine carboxaldehyde and dimethyl malonate, followed by benzylation of the piperidine intermediate afforded A-benzylated piperidine 32. Alkylation of 32 with 3,4-dimethoxybenzyl chloride (33) and subsequent hydrolysis gave dicarboxylic acid 34. Subjection of 34 to strong acid resulted in intramolecular Friedel-Crafts acylation and in situ decarboxylation to provide 3. 

Condensation of tren with 2,3-dihydroxybenzaldehyde, sal (52) (or derivatives), acac, 2-hydroxy-acetophenone (or derivatives), pyridine carboxaldehydes, pyrrole carboxaldehydes and... 

The IR spectra of Co(II), Ni(II) and Cu(II) complexes of Schiff bases derived from condensation of 2-pyridine-carboxaldehyde with DL-alanine, DL-valine and DL-phenylalanine, show that all act as uninegative, bidentate ligands.507 Similar data for complexes of the heterocyclic Schiff base LH2 derived from 1 -amino-5-benzoyl-4-phenyl-li/-pyrimidin-2-one and 3-hydroxy-salicylalde-hyde show that the ligand is tridentate (0,N,0) in M(LH)2 (M = Co, Cu, Zn), but bidentate (N,0) in Ni(LH2)2Cl2.508... 

Holmes et al. [33] reported the solution and polymer-supported synthesis of 4-thiazolidinones 3 and 4-metathiazanones 4 derived from amino acids. A three-component condensation of an amino acid ester or a resin-bound amino acid (glycine, alanine, j8-alanihe, phenylalanine, and valine), an aldehyde (benzaldehyde, o-tolualdehyde, m-tolualdehyde, p-tolualdehyde and 3-pyridine carboxaldehyde), and an a-mercapto carboxylic acid led to the formation of five- and six-membered heterocycles (Fig. 3b). 

Condensation of A-protected pyrrole-2-carboxaldehyde with ethyl a-amino-/3, -diethoxypropionate followed by reduction and cyclization in the presence of TiCU afforded the pyrrolo[2,3-c]pyridine derivative 70 in excellent yield (93T8139). 

Mixed donor ligands. The complex [FeL3]Cl3 (L = acetylhydrazine) contains the ligand in its bidentate form, bonded via the carbonyl and primary amino-groups.Pyridine-2-carboxaldehyde and l,l,l-tris(aminoethyl)ethane react with Fe" via a template reaction to form [Fejlpyljltame) ], in which three molecules of carboxaldehyde have condensed with one molecule of triamine to produce (pyljltame). MeC(CH2N=CH-oc-py)3 the complex cation is octahedral. The complexes [FeL ] (L = l,10-phenanthroline-2-carboxamide, n = 1 or 2) have been isolated they are both six-co-ordinate. Very weak d-d bands have been identified in the spectra of complexes of ot-picolinic acid and quinaldic acid with Fe". ... 

Additional examples of the utility of ring cleavage and recyclization of 4(5Ff)-oxazolones to prepare interesting heterocycles have been described (Scheme 6.16). Ttreatment of 4-aminothymol 53 with 54 in refluxing pyridine yields the 4-imidazolidinones 55 evaluated as antimicrobial and antimbercular agents. The authors listed an extensive series of analogues (25 compounds) but reported a yield for only one example, 55 (63% for Ri = Ph, R2 = 4-MeO—CeKt). Condensation of 2-phenyl-4(5F/)-oxazolone 56 with substituted hydrazines affords excellent yields of the 1,2,4-triazoles 57, important precursors to the previously unknown l(r/)-l,2,4-triazole-5-carboxaldehydes 58. Representative examples are shown in Table 6.3 (Fig. 6.8). 

The amino carbinol pyridines 264, prepared from 263 by DoM reaction and aliphatic or aromatic carboxaldehyde quench, are useful intermediates for condensed naphthyridines 266-268. The thermolytic reaction proceeds via intramolecular Diels-Alder reactions of the aza-orf/io-quinodimethane species 265 (Scheme 79) (84CC1304). 

Another series of macrocydic complexes has been prepared by Busch and co-workers by the condensation reaction of either pyridine-2,6-dicarboxaldehyde or 2,6-diacetylpyridine with various polyamines (Scheme 38). 24,2628,2640 2645 Other examples of template reactions leading to different types of macrocydic complexes are reported in Schemes 39-44.2628 2646 2650 The selfcondensation of l-amino-2-carboxaldehyde in the presence of nickel(II) gives two types of macrocycle (Scheme 45), M51... 

Skolmeistere et al.136 studied the oxidation of 2-methylpyridine and pyridine-2-carboxaldehyde on a V-Mo oxide catalyst and observe that the main products formed in the second case are high-molecular condensation products and that a small amount of 2-picolinic acid is formed directly from the first compound. 

The substituted perhydro-imidazo[l, 5-uJpyridine (113) was prepared in order to test for inhibition of enzymes thymidylate synthetase and dihydrofolate reductase. Pyridine-2-carboxaldehyde was condensed with ethyl-p-aminobenzoate to give the Schiff base (111) which, on sodium borohydride reduction followed by catalytic hydrogenation, resulted in 112. Condensation of 112 with 5-formyluracil gave 113 (70JMC276). 

Oxidation of the pyrazole carboxaldehydes 294 using potassium permanganate in aqueous pyridine gave satisfactory yields of the carboxylic acids 295 (Equation 56) <2001CHE467>. Condensation of AT-alkylpyrazole-4-carbaldehyde 296 with 2,3-bis(hydroxyamino)-2,3-dimethylbutane sulfate, then sodium periodate oxidation of 1,3-dihydroxyimi-dazolidine 297 afforded pyrazolyl nitronyl nitroxides 298 (Scheme 26) <2001ARK55>. Another approach to... 

Fig. 64. Two tetramers. Left, is the iMn,0,(tphpn)3 [ tetramer. Right, LMni (2-OH picpn)2] tphpn = N,N, A+ A+tetrakisfpyridylrnethyl)-1,3-diaminopropan-2-o]. 20Hpicpn is the Schiff-base condensation product of pyridine-2-carboxaldehyde with 1,3-diamino-propan-2-ol. [Reproduced with permission from (334) and (333), respectively. Copyright 1991 and 1996 the American Chemical Society, respectively.]...

The second target, 4-oxo-4H-l-benzopyran-3-carboxylic acids (3) were obtained by Jones oxidation of or hydrolysis of the 3-carbonitrile derivatives ( ) described below (14). The third target, 3-(4-oxo-4H-1-benzopyran-3)acrylic acids (4) were synthesized generally by the Knoevenagel reaction of 3-carboxaldehydes (2) with malonic acid ( 1 ). In the meantime, it was found that the 3-carboxaldehydes ( ), which were able to function as P-dialdehyde compounds, were attacked by amide groups in some cases, to give 2(IH)-pyridone derivatives after condensation with malonic acid derivatives. Thus, condensation of 2 with malonodiamide in pyridine gave initially acrylamide derivatives which were converted into 3-carbamoyl-5-(2-hydroxybenzoyl)-2(IH)-pyridones ( ) (24) ... 

The required iminium ion can be obtained readily by the condensation of an aldehyde with a butenylamine. For example, heating the butenylamine 276 with pyridine-3-carboxaldehyde and an acid catalyst (camphorsulfonic acid, CSA), gave the acetyl nicotine derivative 277 (3.176). The initial iminium ion 278 rearranges to the new iminium ion 279, which is irreversibly trapped in an intramolecular Mannich reaction to give the pyrrohdine 277. 

In a synthesis of a potent selective inhibitor of Factor Xa, modified Ugi four-component condensation between tetra-O-pivaloyl- -D-glucopyranosylamine, pyridine-4-carboxaldehyde, formic acid, and ethyl isocyanoacetate gave the product 208 in high yield and with 81% de. This was subsequently converted to the desired peptidomimetic 209. ... 

Sol 1. (a) The condensation of pyridine-3-carboxaldehyde (I) with 2-methyl-1-(methylamino)but-3-en-2-ol (II) gives the iminium ion intermediate (III). Ill undergoes [3,3] sigmatropic shift to give another iminium ion intermediate (IV), which is irreversibly trapped in an intramolecular Mannich reaction to give the pyrrolidine derivative V. 

A review has covered mainly the preparation of aldehydes from carbon monoxide by electrophilic aromatic substimtions involving superacids. In HF-SbFs, some polynuclear aromatic compounds are diformylated. When pyridine-3-carboxaldehyde is compared with benzaldehyde in acid-catalysed condensation reactions with benzene and substituted benzenes to form diaryl-3-pyridylmethanes, it is found to be... 

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