Pyridine-3-carboxylic acids, 2-hydroxy

Chemical Name 3-Pyridine carboxylic acid compounded with 3,7-dihydro-7-[2-hydroxy-3-[(2-hydroxymethyl)methylamino] propyl] -1,3-dimethyl-1 H-purlne-2,6-dlone(1 1)... 

Nicotinic acid (3-pyridine carboxylic acid or niacin) nicotinamide (nicotinic acid amide), niacinamide, 3-pyridine-carboxylic acid amide Thiamines, hydroxy-ethylthiamine... 

The conclusions to be reached from these data are, chiefly, that whilst hydroxy-and mercaptopyridines and pyridine carboxylic acids exist predominantly in the Z forms (i.e. as pyridones, pyridthiones and zwitterions), aminopyridines prefer the NM forms (that is, they are mainly amines and not iminesj. The spectroscopic evidence supporting these conclusions has already been discussed, and this tautomerism is further discussed below. 

The reduction of pyridine-carboxylic acids has been mentioned already (pp. 258, 263), and it has been seen that electrolytic reduction or reduction with zinc and acetic acid can give methyl- or hydroxymethylpyridines. Whilst the electrolytic reduction of benzoic acid to benzyl alcohol is well known, benzene-carboxylic acids are generally not so readily reduced as the pyridine-carboxylic acids. Two other additional cases might be quoted. A dichloropyridine-carboxylic acid has been reduced by phosphorus and hydriodic acid to a dichloromethylpyridine , and 2,6-dichloropyridine-4-carboxylic acid with zinc and acetic acid gives 2,6-dichloro-4-hydroxy-methylpyridine . Isonicotinic acid is reduced to the alcohol by tin and hydrochloric acid . 

Ethers of benzenepentol have been obtained by Dakin oxidation of the appropriately substituted acetophenone. Thus, the oxidation of 2-hydroxy-3,4,6-ttimethoxyacetophenone and 2-hydroxy-3,4,5-ttimethoxyacetophenone with hydrogen peroxide ia the presence of alkali gives l,2-dihydroxy-3,4,6-ttimethoxybenzene and l,2-dihydroxy-3,4,5-ttimethoxybenzene, respectively further methylation of these ethers yields the pentamethyl ether of benzenepentol (mp 58—59 degC) (253). The one-step aromatization of myoinositol to produce esters of pentahydroxybenzene is achieved by treatment with carboxylic acid anhydrides ia DMSO and ia the presence of pyridine (254) (see Vitamins). 6-Alkyl- or... 

Selenolo[2,3-b]pyridine-2-carboxylic acid, 3-hydroxy-synthesis, 4, 1034 Selenolopyridines, 4, 1034—1036 H NMR, 4, 1035, 1036 Selenolo[2,3-c]pyridines synthesis, 4, 1035 Selenolo[3,2-b]pyridines deuteriodeprotonation, 4, 1035 synthesis, 4, 1034 Selenolo[3,2-c]pyridines synthesis, 4, 1035 Selenolo[2,3-b]pyrroles ionization potentials, 4, 1046 Selenolo[3,2-b]pyrroles ionization potentials, 4, 1046 Selenolo[3,4-c]pyrroles non-classical... 

P-Acetoxy-5-hydroxy-B-mrcholestan-6-carboxylic Acid 5,6-Lactone (TO)."" A solution of 5 g (0.011 mole) of keto acid (69), 4.4 g of benzoyl chloride and 10 ml of anhydrous pyridine is allowed to stand for 3 days at room temperature. After a short period the mixture turns red-brown and at the end of the reaction the dark semi-solid mass is poured into 200 ml of water and extracted with two 100 ml portions of ether. The ethereal extracts are washed twice with equal portions of 5 % sodium hydroxide and water, dried and the ether evaporated. The red sirupy residue is mixed with 10 ml of methanol and a brown solid separates immediately. After standing for 1 hr the solid is removed by filtration and washed with methanol. A second crop is obtained upon concentration of the filtrate. The combined crops are recrystallized twice from methanol to give (70) as white needles mp 124-125° yield 2.8 g (58 %). 

Jaffe to pyridine-3- and -4-carboxylic acids and to 3-hydroxy-pyridine for which values of the a constants are much more certain. 

Treatment of alkyl 9-benzyloxycarbonyl-3-methyl-6-oxo-2/7,6//-pyr-ido[2,l-f ][l,3]thiazine-4-carboxylates with BBr3 in CH2CI2 at -70 °C for 0.5-1 h and at room temperature for 3h yielded 9-carboxyl derivatives. The decarboxylation of these acids was unsuccessful. Hydrolysis of diethyl cA-3,4-H-3,4-dihydro-3-methyl-6-oxo-2//,6//-pyrido[2,l-f ][l,3]thiazine-4,9-dicarboxylate in aqueous EtOH with KOH at room temperature for 3 days yielded 4-ethoxycarbonyl-3,4-dihydro-3-methyl-6-oxo-2//,6//-pyrido-[2,l-f ] [1,3]thiazine-9-carboxylic acid (00JCS(P1)4373). Alkyl 9-hydroxy-methyl-3-methyl-6-oxo-3,4-dihydro-2//,6//-pyrido[2,l-f ][l,3]thiazine-4-car-boxylates were O-acylated with AC2O and (PhC0)20 in pyridine at room temperature for 12-48h. 

A more general route to 4-acetoxy-l,3-dioxanes utilizes the reductive acylation of l,3-dioxane-4-ones [46] (Scheme 21). l,3-Dioxane-4-ones 126 are prepared from the corresponding -hydroxy carboxylic acids. Low temperature reduction with DIBALH generates a diisobutylaluminum hemiacetal (127) which undergoes acylation in situ with AC2O in the presence of pyridine and DMAP. This method allows for the preparation of a wide range of 4-acetoxy-l,3-dioxanes, without the problem of a-epimerization. This method also represents a general approach to acylic a-acetoxy ethers, which are themselves useful synthetic intermediates [47,48]. 

The commercial extractants currently used fall into the following categories 297 a-hydroxy-ketox-imes, phenolic-oximes,298 dialkylsulfides, esters of pyridine mono and di-carboxylic acids,299- 1 alkyl derivatives of 8-hydroxyquinoline,79,302,303 trialkylamines,304,305 alkyl derivatives of aniline,306 aliphatic ethers, and ketones.307-309... 

More recently, some AMPA agonists showing unusual stereostructure-activity have been compared using the commercial docking package Glide (21). These include the enantiomers of 2-amino-3-(3-hydroxy-l,2,5-thiadiazol-4-yl)propionic acid (TDPA) and 2-amino-3-hydroxy-5-phenyl-4-isoxazolyl propionic acid (APPA) (28), as well as 3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-5-carboxylic acid (5-HPCA). 

In the early days, greatest interest was focused on the acid-catalyzed hydrolysis (by hydrochloric acid in the presence of 2,4-dinitrophenylhydrazine) of Reissert compounds to aldehydes and the corresponding heterocyclic carboxylic acid derivatives. This reaction is fairly general for compounds of quinoline (178) and isoquinoline (179) (Table 18), but it is not applicable to pyridines as they rarely form Reissert compounds. The 3-hydroxyquino-line Reissert compound does not yield benzaldehyde, probably because acylation of the 3-hydroxy group prevents formation of the required cyclic intermediate (180). Some nitroquinolines and isoquinolines give low yields of benzaldehyde. Rather curiously, disub-stituted quinoline Reissert compounds yield less of the aldehyde than of the corresponding... 

Oxetanones can be generally prepared by displacement processes on various /3-substituted carboxylic acids or by halolactonization of /3,y-unsaturated acids. A very general and reliable method consists of treatment of a /8-hydroxy acid with benzenesulfonyl chloride and pyridine at 0°C (equation 91). The yields of /3-lactones are usually in excess of 80% (79JOC356, 74JOC1322). An alternative method involves cyclization of the benzenethiol ester of a /3-hydroxy carboxylic acid by means of mercury(II) methanesulfonate in acetonitrile (equation 92). The yields were excellent in the two cases reported (76JA7874). 

Chloro-4-hydroxy-2-methyl-1,1 -dioxo-1,2-dihydro-1 l6-thieno[2,3 e][1,2]thiazine-3-carboxylic acid pyridin-2-ylamide, 6-chloro-4-hydroxy-2-methyl-/V-(2-pyridyl)-2H-thieno[2,3-e]-1,2-thiazine-3-carbox-amide-1,1-dioxide, CnH,oC N30AS2, Mr 371.81, mp 225-230 °C (decomp.)... 

The methoxy group in 7-methoxy,2 7-methoxy-6-methyl,41 and 7-methoxy-4-methylisatin41 has been cleaved to the corresponding hydroxy group with pyridine hydrochloride, while treatment with sodium hydroxide cleaves the 6-methoxy group of 5-chloro-6,7-dimethoxy-l-methylisatin.48 5-Acetamidoisatins have been hydrolyzed to 5-aminoisatins.30 Isatin carboxylic acids have been converted to amides and esters by means of standard procedures.52,53... 

The synthetic procedures mentioned in this section certainly do not cover all the known routes leading to depsipeptides. Some seldom-used or potentially useful but not yet practically employed techniques are inevitably missing. For example, such potential might be attributed to the method of carboxylic acid activation by pyrocarbonates suggested by Pozdnev in 1992J120i In particular, this author has shown in some model cases that Boc20 in the presence of pyridine and a catalytic amount of 4-(dimethylamino)pyridine forms an ester link between an amino acid and an a-hydroxy acid in 80-90% yield. 

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