Pyridine-3-carbaldehyde

Chelating aldehydes such as 2-pyridine carbaldehyde and 2-dimethylamino benzaldehyde improve the stability of the aldehyde complexes via N,0 chelation. NMR studies show that the complexes are present in solution without an excess of aldehyde and can be formed in the presence of donor ligands. The X-ray structures showed longer and weaker Zn—O bonds when more than one chelating ligand was present. IR demonstrates the variation in C=0 bond strengths and how the environment of the zinc ion will influence potential catalytic activity via reaction rates or pathways. Tetrahedral chelate complexes, and octahedral bis- and tris-chelate complexes, were isolated.843... 

The introduction of a carbamoyl group to the 5-position of chiral 3-pyridyl alkanol enhances its efficacy as asymmetric autocatalyst. (S)-5-Carbamoyl-3-pyridyl alkanols 61 are automulti-plied with up to 86% ee in the enantioselective addition of i-Pr2Zn to 5-carbamoyl-3-pyridine-carbaldehyde 60 (Scheme 9.32) [60]. The enantioselectivity depends on the structure of the substituent on the nitrogen atom of the amide. A bulky t-Pr substituent is efficient for achieving high enantioselectivity. The amplification of the enantiopurity of 61 to a certain degree is also observed [61]. 

In addition to its use in the preparation of the square pyramidal Mo and W complexes 38 and 39, the Schiff base derived from pyridine carbaldehyde-(2) and S-(—)-a-phenyl ethyl amine54 was also used for the synthesis of optically active Co complexes of the tetrahedral type60. Unlike the Mo and W compounds, the separated Co diastereoisomers 40a, 40b one of which is shown in Scheme 20, are optically stable. The rigidity of the tetrahedral Co complexes and the nonrigidity of the square pyramidal Mo and W complexes give a further indication of the intramolecular character of the epimerization of 38 and 39. 

In order to study substituent effects on the epimerization rate of square pyramidal compounds of the type CsHsM(CO)2LL, we synthesized the derivatives 41-49 by using instead of pyridine carbaldehyde-(2) the corresponding aldehydes for the condensation reaction with S-(-)-a-phenyl ethyl amine. In all the cases 41-49 the resulting pair of diastereoisomers could be separated into the optically active components a and b63-65 the a series is depicted in the formulas of Scheme 21. 

The presence of N-atoms in the aromatic part of the aldehyde appears essential for chiral amplification. With only one nitrogen, such as in the case of 3-pyridine carbaldehyde, autocatalytic kinetics but no chiral amplification effect has been observed [24,25]. In the case of 3-quinoline carbaldehyde, i.e., in the presence of two nucleophilic centers, autocatalysis as well as moderate chiral amplification were reported [26,27]. Highest amplification capacity is observed in the presence of two N-atoms in the aromatic part of the aldehyde, where for the substituent at the 2-position the amplification capacity increases H < CH3 < f- Bu - C=C -, i.e., with the size and rigidity of this group. So far, detailed studies that could relate the given observations to the possible mechanism of chiral amplification in Soai s reaction are still to be carried out. 

Cleavage of a thiazolidine ring is observed151 in the reduction of the condensation product between cysteine and pyridoxal, 2-(2-methyl - 3 - hydroxy - 5 - hydroxymethyl - 4 - pyridyl)thiazolidine - 4 -carboxylic acid (131). The reduction is best understood when the compound is considered as a derivative of 4-pyridine carbaldehyde... 

Fig. 3. Rate of oxidation of P-picoline (1 -3) and selectivities for nicotinic acid (4), 3-pyridine-carbaldehyde (5) and CO2 (6) versus conversion of P-picoline. 0 - 250°C A - 270°C - 300°C.

In the classical lithiation of triazolopyridines at —40 °C with LDA in THF, the 7-lithio derivatives 71 formed are trapped by electrophiles giving 7-substituted triazolopyridines 138a-d. When the starting material was 3-(2-pyridyl)-triazolopyridine 33,19a was formed (Scheme 32), using as electrophiles 2-pyridine carbaldehyde (98T15287), 2-cyanopyridine, and in better yield, ethyl picolinate (04T5785). 

Hughes M, Prince RH (1978a) Metal ion function in alcohol dehydroge-nases-I. Metal-dependent reduction of pyridine carbaldehydes. J Inorg Nucl Chem 40 703-712... 

Hughes M, Prince RH, Wyeth P (1978) Metal ion function in alcohol dehydrogenases-II. The metal binding sites of pyridine carbaldehyde and N-benzyldihydronicotinamide. J Inorg Nucl Chem 40 713-718 Huskey WP, Schowen RL (1983) Reaction coordinate tunneling in hydride-transfer reactions. J Am Chem Soc 105 5704-5706 Inouye Y, Oda J, Baba N (1983) Reduction with chiral dihydropyridine reagents. In Morrison JD (ed) Asymmetric synthesis, vol 2. Academic Press, New York, p91... 

Epimerization of diastereoisomers of related complexes [M(CO)2(LL )( -C5H5)] (M = Mo or W) where LL is a bidentate ligand derived from Schiff bases of benz-aldehyde (5) follows first-order kinetics with the activation parameters given in Table 2. In these cases the epimerization process, as with pyridine carbaldehyde... 

Amines While 3-pyrrolylaldehydes or ketones and 2-pyridyl ketones are transformed into rearranged and/or reduced McMurry products [50, 51], 2-pyrrolylalde-hydes or ketones and 3-benzoylpyridine can be coupled by low-valent titanium reagents, as shown by the synthesis of compounds 34, or 35 and 36, respectively [50-53] (Figure 6.6). Coupling of 3-pyridine carbaldehydes gives the dipyridyl... 

In at least one case, the standard Bucherer-Bergs conditions gave rise to oxazole rather hydantoin. Specifically, when 5-benzyloxy-pyridine-2-carbaldehyde (11) was treated with potassium cyanide, ammonium chloride, and ammonium carbonate in boiling ethanol/water, 5-amino-oxazol-2-ol 12 was obtained. Subsequent heating of oxazole 12 with acetic acid at reflux overnight then produced the Bucherer-Bergs product, hydantoin 13. ... 

An interesting intermediate 30 was proposed to result from the sequential addition of pyridine to tetrachlorocyclopropene (31). Compound 30 represents an alkyl nitrogen ylide with two 1-chloroalkyl pyridinium moieties in the same molecule. Pyridines with electron-withdrawing groups and heterocycles with an electron-deficient nitrogen, for example, pyridine-3-carbaldehyde or quinoline, react with 31 to yield the corresponding mono-substituted products 32a and 32b (83JOC2629) (Scheme 8). 

Ligand abbreviations bi = 2,2 -bi-2-imidazoline bt = 2,2 -bi-2-thiazoline bpy = 2,2 -bipyridine phen = 1,10-phenanthroline phy = l,10-phenanthroline-2-carbaldehyde phenylhydrazone bpp = 2,6-bis(pyrazol-3-yl)pyridine paptH = 2-(2-pyridylamino)-4-(2-pyridyl)thiazole 2-pic = 2-picolylamine L = macrocyclic ligand derived from condensation of 2,6-diacetylpyridine with 3,6-dioxaoctane-1,8-diamine Hjthpu = pyruvic acid thiosemicarbazone Hjthpx = pyridoxal thiosemicarbazone salen = dianion of W,iV -ethylenebis(salicylideneimine) H2fsa2en = dianion of fV,JV -ethylenebis(3-carboxysalicylaldimine). 

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