Pyridine-3-carboxaldehyde

An additional means of performing a selective cross-benzoin was reported in 2001 when Mnrry and co-workers expanded benzoin methodology to include trapping of acyl imines XIX formed in situ (Scheme 6) [53], The authors chose to use a-amido sulfones due to their stability and the relative ease of acyl imine liberation. The parent reaction combines pyridine 4-carboxaldehyde 51 and tosylamide 52 in 98% yield in the presence of pre-catalyst 54 and triethylamine (Scheme 6). 

Mol. wt. 279.30, m.p. 100-101°. The reagent is obtained by reaction of pyridine-4-carboxaldehyde with methyl benzenesulfonate in refluxing benzene (83% yield). 

The other trends in values for the various Rs in Table V are consistent with the trends in pairwise interaction contributions to heats of formation evaluated by Allen (19) and discussed by Hine (20). For example, pyronin has a C-C-X pair interaction in place of an O-C-X interaction for pyridine-4-carboxaldehyde for X = OH this difference favors the aldehyde adduct by approximately 7 kcal, although for other Xs, the difference is somewhat smaller. Thus, the values given for the aldehyde are smaller than those for pyronin. We have already pointed out that steric effects are expected in the triarylmethyl derivatives and that the comparison of these with pyronin derivatives are consistent with that expectation (1). 

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. ... 

Scheme 13) under similar conditions to those discussed earlier (cf. Scheme 11) to liberate a-amino lactone 75, subsequent transamination using the methiodide of pyridine-4-carboxaldehyde, DBU, and DMF in CH2CI2 served to unveil a-keto lactone 24 in 70% yield, presumably through the defined mechanism. With this critical motif in place, all that now remained was to incorporate... 

Pyridine-4-carboxaldehyde added at 0° to an aq. soln. of chloramine, and the product isolated immediately 4-pyridinalchlorimine (Y 71%) dissolved in abs. methanol, treated with triethylamine, ice-cooled to keep the soln. below reflux, and the product isolated after 1 hr. isonicotinonitrile (Y 92%). F. N-chlorimines s. E. J. Poziomek, D. N. Kramer, and W. A. Mosher, J. Org. Ghem. 25, 2135 (1960). 

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. 

Pstyrylquinoline [13362-63-5]. This chemistry is also useful with the pyridine carboxaldehydes to form adequate yields of the corresponding... 

Another class of new ligands was prepared in quantitative yields by Feringa et al., in 1997, by reaction between a-mercapto acids, aniline and 2-pyridine-carboxaldehyde." These pyridyl-substituted thiazolin-4-one ligands were further involved in the copper-catalysed conjugate addition of ZnEt2 to 2-cyclohexenone,... 

The surface-enhanced Raman spectra (SERS) provide information about the extent of protonation of the species adsorbed at the silver/aqueous solution interface. The compounds investigated were 4-pyridyl-carbinol (1), 4-acetylpyridine (2), 3-pyridine-carboxaldehyde (3), isonicotinic acid (4), isonicotinamide (5), 4-benzoylpyridine (6), 4-(aminomethyl)pyridine (7) and 4-aminopyridine (8). For 1, the fraction of the adsorbed species which was protonated at -0.20 V vs. SCE varied with pH in a manner indicating stronger adsorption of the neutral than the cationic form. The fraction protonated increased at more negative potentials. Similar results were obtained with 3. For all compounds but 4, bands due to the unprotonated species near 1600 cm-1 and for the ring-protonated species near 1640 cm-1 were seen in the SERS spectra. 

In comparison to 1 and 2, the SERS spectra of 3-pyridine-carboxaldehyde (3) are relatively featureless (8). The spectra are dominated by the symmetrical ring-breathing mode at 1030 cm 1 but the features associated with the unprotonated species (about 1600 cm ) and the protonated species (about 1640 cm 1) are definitely present along with a weak carbonyl band at about 1710 cm . The variation in the relative population of protonated species is as expected (Figure 5) though a detailed analysis reveals some surprises. As can be seen in Figure 5, about equal intensities of the 1600 and 1640 cm bands are obtained at pH = 3.86, near the pKa (3.73 (9)). However, the band associated with the unprotonated pyridine persists at pH = 1.3, where less than 1J of the solution species remains unprotonated. 

At the most negative potentials, the protonated form of 3 appears to desorb as seen also with 1 and 2. For 4-pyridine-carboxaldehyde, this desorption has been correlated with the desorption of chloride (6) suggesting that the cation and chloride ion are coadsorbed. 

Pyridylcarbinol, 4-acetylpyridine, 3-pyridine-carboxaldehyde and 4-aminomethylpyridine were obtained from Aldrich Chemical Company (Milwaukee, Wisconsin) and were purified by distillation at reduced pressure. 4-Benzoylpyridine was recrystallized from ethanol. 4-Aminopyridine (G. Frederick Smith Chemical Company), isonicotinic acid (Aldrich) and isonicotinamide (Aldrich) were used as received. Triply distilled water was used. All other reagents were analytical reagent grade. 

Ru(H20)(bpy)(app)]Clj (H3app=A-(hydroxyphenyl)pyridine-2-carboxaldimine) is made by reaction of RuClj with 2-aminophenol and 2-pyridine carboxaldehyde under reflux followed by addition of (bpy). Infrared and electronic spectra were measured, and the room-temperature magnetic moment is 1.98 B.M. The system [Ru(H30)(bpy) (app)] +/TBHP/(BTBAC)/CH3Clj (BTBAC=benzyltributylammonium chloride) oxidised benzyl alcohol to benzaldehde and alkenes to mixtures (e. g. cis- and trans-stilbene to benzaldehyde and cis- and tranx-stilbene oxides). Alkanes gave mixtures... 

Another system in which ring-formation has been considered to be manifested on polarographic curves is the reduction of pyridoxal (77, 80). The reduction wave of this compound changes with pH and the observed plot is similar to that shown in Fig. 22. This dependence can be explained either by hydration (as for other pyridine carboxaldehydes), or by hemiacetal formation. The same two interpretations can be applied to electronic spectra. A comparison with the behaviour of pyridoxal-5-phosphate can contribute to the solution of this problem. With this ester the formation of the hemiacetal form is impossible and practically no current decrease in acidic solutions can be observed. Hence it can be concluded that the decrease in the limiting current of pyridoxal is due to ring formation. Nevertheless, the possibility of some participation by a dehydration reaction cannot be completely excluded, for it is possible to assume that the introduction of a phosphoric acid residue into position 5 either shifts the equilibrium towards the dehydrated form or increases the rate of dehydration. 

Heterocyclic and aromatic aldehydes (e.g., furan-2-carboxaldehyde, thiophen-2-carboxaldehyde, the pyridine carboxaldehydes, benzaldehyde, and diverse substituted benzaldehydes). 

The spots were located by examination under UV light or spraying with one of following solutions (detection limits in yg) fluorescamine (0.5), ninhydrin (1), NBP followed by heating and treatment with a base (5) [51,63a], and 0.5% iodine in chloroform. Visualization using 4-pyridine-carboxaldehyde 2-benzothiazolyl hydrazone has been described under 5.2.1. 

Figure 10.2 illustrates selected examples of these epoxide products. Aromatic and heteroaromatic aldehydes proved to be excellent substrates, regardless of steric or electronic effects, with the exception of pyridine carboxaldehydes. Yields of aliphatic and a,/ -unsaturated aldehydes were more varied, though the enantio-selectivities were always excellent. The scope of tosylhydrazone salts that could be reacted with benzaldehyde was also tested (Fig. 10.3) [29]. Electron-rich aromatic tosylhydrazones gave epoxides in excellent selectivity and good yield, except for the mesitaldehyde-derived hydrazone. Heteroaromatic, electron-poor aromatic and a,/ -unsaturated-derived hydrazones gave more varied results, and some substrates were not compatible with the catalytic conditions described. The use of stoichiometric amounts of preformed sulfonium salt derived from 4 has been shown to be suitable for a wider range of substrates, including those that are incompatible with the catalytic cycle, and the sulfide can be recovered quantitatively afterwards [31]. Overall, the demonstrated scope of this in situ protocol is wider than that of the alkylation/deprotonation protocol, and the extensive substrate...

Scheme 10.10 Synthesis of CPD-840 involving asymmetric epoxidation as a key step. Reagents and conditions (a) K2CO3, cyclopentyl bromide, DMF, 97% (b) NaBH4, MeOH, 99% (c) ent-4, HBF4, Et20, rt, 4 h, 80% (d) EtP2-base, CH2CI2, —78 °C, 15 min, then 4-pyridine carboxaldehyde, —78 °C, 1 h, 89%, (trans cis = 7 3), >98% ee ...

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. 

Controlled catalytic vapor-phase oxidation converts, for example, 2-, 3-, and 4-picolines into 2-, 3-, and 4-pyridine carboxaldehydes. 

Salicylaldehydes and 2-pyridine carboxaldehyde which cannot be normally used with Lewis acids because of their coordination to metal may be used as substrates with Lu triflate as a catalyst [156]. 

Reaction of [Ru(NH3)4(OH2)2]2+ with L (L = 2-pyridine carboxaldehyde,263 2-pyridine alcohol4763) yields the complexes [RuuL(NH3)4]2+. These products can be interconverted by oxidation of the pyridine alcohol derivative (48) to the acetyl pyridine complex (49) (Scheme 18) 4763 The complexes [Ru(NH3) L]+ (n = 4,5 LH = pyrazinecarboxylic acid) have been generated in which L can be mono- or bi-dentate.476b... 

Quinuclidinone hydrochloride (0.49 mol) was treated with potassium hydroxide (0.54 mol) dissolved in 420 ml methyl alcohol and then stirred 30 minutes at ambient temperature. 3-Pyridine-carboxaldehyde (0.54 mol) was then added and the mixture stirred for an additional 16 hours. Solid cakes, which formed on the flask walls, were broken up and dissolved with the addition of 390 ml rapidly stirring water. The mixture was kept cooled to 4°C overnight and a precipitate formed, which were collected by filtration. These crystals were then washed with water, air dried, and 80 g product isolated as yellow solid. A second product crop of 8 g was obtained by reducing the filtrate volume by 90%, so a total product yield of 82% was observed. 

The product from Step 2 (10 mmol) was mixed with 2-pyridine-carboxaldehyde (10 mmol) and 200 ml benzylamine in 12 ml HO Ac, refluxed 3 hours, cooled, and treated with 50 ml diethyl ether. Any precipitation was removed by filtration. The filtrate was diluted with additional diethyl ether, washed successively with NaHC03, sodium bisulfite, HCl, and 35 ml water. The mixture was concentrated and the product isolated as solid. 

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... 

A synthesis of 4-alkyl-3-pyridinols (55) from 3-benzyloxypyridine (52) utilizes a copper-catalyzed Grignard reaction. The dihydropyridine intermediates 53 are aromatized to 4-alkyl-3-benzyloxypyridines (54), which on hydrogenolysis provide the pyridinols 55 (85JHC1419). Substitution at the 4-position of 3-pyridinecarboxaldehydes can be achieved via 1-acylpyri-dinium salt 56. The intermediate acetal 57 is hydrolyzed to give pyridine-carboxaldehyde 58 (84H339). 

Tsang et find for 4-pyridine-carboxaldehyde adsorbed on a rough silver surface in a tunnel junction layout, that the intensity is constant in the red to green region and strongly decreases in the blue. They use a Raman line of quartz as a reference, but that does not correct for the absorbance in the silver overlayer in this system. 

Prien et al. [18] have synthesized 3-hydroxy-2-methylidene propionic acids on hydrox-yethyl resin via a Baylis-Hillman reaction by using aldehydes bearing electron-withdrawing groups, for example nitrobenzaldehyde, trifluoromethylbenzaldehyde and pyridine-carboxaldehyde. 

Thiazolidines bearing a pyridine substituent in position 2 36-39 are useful as ligands for rhodium-catalyzed hydrosilylations (Section D.2.3.1.). They are readily prepared from 2-pyridine-carboxaldehyde or 2-acetylpyridine by cyclization with L-cysteine methyl or ethyl ester22. The compounds are diastereomeric mixtures at position 2, but this does not hamper their application as chiral ligands, as rapid equilibration occurs in solution. One of these ligands 38 (PYTHIA)... 

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). 

Hirl] UHF calculation of spin densities using parameterization scheme of Beveridge and Hinze. i9 ) McLachlan calculation of spin densities. - ESR spectrum shown for corresponding radical generated from 2-vinylpyridine. 1 5 Or electrolytic reduction of 4-pyridine-carboxaldehyde N-oxide. 

The best reaetion eonditions were used with other aromatic aldehydes and yields and ees were similar to those observed with benzaldehyde except for pyridine carboxaldehyde. In this ease, nitrogen atom of pyridine ring was suspected to be too chelating. Excellent enantioseleetivity (93%) was also obtained with an enolizable aldehyde, -octanal. Furthermore the eatalyst could be recovered by simple filtration and could be reused five times without loss of eatalytic activity. 

Metal ions sorption by 2-pyridine carboxaldehyde phe-nylhydrazone supported by chemical binding on a silica surface were confirmed to the Langmuir isotherm. The modified phase was used and applied as a metal-ion extractant for determination of trace amounts of iron, cobalt, nickel, and copper. The relative orders of the Langmuir constants K and the column retention capacity factors K for the four transition metal ions are the same as the natural order of the stabihty constants for their metal chelates Fe(II) < Co(II) < Ni(II) < Cu(II). The structure is given in Scheme 5. 

---