Pyridine esters

Guengerich FR Peterson LA, Bocker RH. Cytochrome P-450-catalyzed hydroxylation and carboxylic acid ester cleavage of Hantzsch pyridine esters. J Biol Chem 1988 263(17) 8176-8183. 

Ethers, Esters, and Carboxylic Acids.— Monosulphates of partially formylated bile acids were prepared using SOs-EtsN complex in pyridine. Esters of testosterone and 19-norethisterone and hindered carboxylic acids were conveniently prepared by adding the alcohols in pyridine to a solution of the... 

Now a second molecule of L vanoacctate condenses with the pyridine. The nitrogen of the pyridine attacks the ester and the enoUate) of the pyridine ester attacks the new nitrile. Take your choice on the order of events. 

The hydride is an excellent reagent for drying bydrocaibons, ethers (inclwling dioxane and tetrahydroftirane), amines (including pyridine), esters, the butanols (but not methanol or ethanol, which form alkoxides). Since the hydride is an effective condensation catalyst, it should not be used to dry aldriiydes, reactive ketones, acids, or acyl halides. Chlorides and bromides should be dried over calcium hydride only at moderate temperatures. 

Of the N-alkylcarbamates only the aryl esters of N-alkylcarbamic acid possess herbicidal activity. The herbicidal activity of N-alkylcarbamic acid alkylesters and of the heterocyclic derivatives of N-alkylcarbamic add is mentioned only in the patents literature, but these latter derivatives have not found agricultural application. Examples are the N-dimethylcarbamic acid enol esters proposed by Whetstone and Kuddema (1959) and the N-methylcarbamic add pyridine esters proposed by Johnston (1964). 

This methodology has recently been applied to a total synthesis of the antitumor antibiotic streptonigrin (24).35 On cycloaddition with a dehydro-hydantoin, diene 23 afforded a 3 1 mixture of regioisomeric adducts (Scheme 2-V). The major isomer was aromatized to a pyridine ester, which was transformed in several steps to the natural product. 

Iithio-3-ethoxypyridine, obtained by the reaction of 3-ethoxypyridine with n-butyl-lithium and TMEDA in THE at — 40 °C, reacts with a wide range of electrophiles to give 2,3-disubstituted pyridines. Esters (R COOR ) are obtained by the reaction of 5-2-pyridylthioates (2-CsH4N-S-COR ) with lithium dialkyl-cuprates (R jCuLi) under oxygen. The reaction of these substrates in a nitrogen atmosphere is known to produce ketones (R COR ). 

Kudo, S., M.G. Okumura, and T. Ishizaki (1999), Cytochrome P-450 isoforms involved in carboxylic acid ester cleavage of Hantzsch pyridine ester of pranidipine. Drug Metab. Dispos. 27, 303-308. 

In a related process an ortho bromo ester is coupled with l-tri- -butylstannyl-2-ethoxyethene then acid used to close the ring the example below shows how this sequence is applied to a pyridine ester. 

When the proper conditions were employed, the 3/f-azepine (XI-4) was converted to the pyridine ester XI-5 in good yields." ... 

Esters of pyridine-carboxylic acids react normally with compounds containing activated methylene groups. The reactions are valuable, for example as routes to acylpyridines. The ethoxide-catalysed condensation of ethyl pyridine carboxylates with ethyl acetate has often been described early work suggested that esters of nicotinic acid gave lower yields than their isomers, but this is not so . Many esters other than ethyl acetate have been used and a number of substituted pyridine esters > Condensations with picolines to give desoxypyridoins are of practical value (p. 380). 

Ethylene chlorohydrin, DMSO, formic acid, W Bzn./acetone, bzn./alcohol, chloroform, pyridine, esters Cellosolve ", dioxane, ethanol, methanol, W (< 45 C)... 

Our quantum chemical calculations confirm the structure of 5-amino-2-methoxy-pyridine ester amide of squaric acid ethyl ester and a comparison between the predicted and observed bond lengths and angles reveals a satisfactory correlation with differences of less than 0.078 A and 7.6(7)°, respectively. Two distinct stable conformers of 5-ami-no-2-methoxypyridine ester amide of squaric acid ethyl esto exist, differing by internal rotation around the C3-04 bond, where C6-04-C3-N5 is equal to 0.0° and 178.1°, respectively. When energies are corrected for zero point vibrational energy contributions, the first conformer is more stable by 6 kJ/mol and is characterized by the flat geanetry and a maximal deviation from total planarity of 10.3°. The ab initio (MP2/6-311++G )... 

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