Pyridine-3-carboxylic acid, 2-chloro

Later Gronowitz and Maltesson reported the extension of this method to the preparation of thieno[2,3-6]thiophene (1) derivatives. A mixture of 3-(3-thienyl)acrylic acid, thionyl chloride, and pyridine was heated for 24 hours. 2-Chloro-3-(3-thienyl)-acrylic acid (4.5%), 3,5-dichlorothieno[2,3-6]thiophene-2-carbonyl chloride (99) (9.5%), 3-chlorothieno[2,3-Z)]thiophene-2-carbonyl chloride (100) (79.1%), and other compounds were detected by GLC among the reaction products [Eq. (31)]. Hydrolysis of the reaction mixture gave 3-chlorothieno[2,3-Z>]thiophene-2-carboxylic acid in 63% yield dechlorination of the latter by copper in propionic acid converted it into thieno[2,3-6]thiophene-2-carboxylic acid. 

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 amino groups of isomeric 5-aminomethyl-8-chloro-6-phenyl-3-methyl-l-oxo-1/7- and -l-methyl-3-oxo-3//-pyrimido[l,2-a]quinolines were acylated with acetic anhydride at room temperature for 1 h (79CPB2927). 5,8,9-Trihydroxy-2,3-dihydro-l//-pyrimido[l,2-a]quinoline-l-carboxylic acid was acylated with acetic anhydride in pyridine at room temperature for 24 h (87T2261). 

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... 

Numerous syntheses involving formation of the thiophene ring have been reported. Nucleophilic substitution by ethyl mercaptoacetate of 2-chloro-3-cyanopyridine with subsequent base-promoted cyclization yields ethyl 3-aminothieno[2,3-i]pyridine-2-carboxylic acid, which is easily transformed by standard methods into the parent compound (258 Scheme 63) (74JHC975, 76JHC273). 

Thieno[2,3-6]pyridine-5-carboxylic acid, 4-chloro-2-methyl-... 

The alcohol 177 was converted to starting substrates oxazolidinone 178 by acylation followed by reduction of the azide function along with cyclization. Oxazolidinone 178 was protected with f-butylpyrocarbonate-4-(dimethylamino) pyridine (DMAP) and triethylamine, which was further subjected to reductive cleavage of the benzyl ester unit to afford carboxylic acid 179. The treatment of 179 with solution of l-chloro-/V./V,2-trimethyl-1-propenv I airline resulted in the easy formation of the corresponding acid chloride which on reaction with imine in the presence of triethylamine provided the stereoselective formation of spiro-p-lactam 180. 

First, 1 2 metal complexes of (mainly mono-) azo dyes, without sulfonic or carboxylic acid groups, and trivalent metals (see Section 3.11). The metals are preferably chromium and cobalt nickel, manganese, iron, or aluminum are of lesser importance. Diazo components are mainly chloro- and nitroaminophenols or amino-phenol sulfonamides coupling components are (3-naphthol, resorcinol, and 1-phe-nyl-3-methyl-5-pyrazolone. Formation of a complex from an azo dye and a metal salt generally takes place in the presence of organic solvents, such as alcohols, pyridine, or formamide. An example is C.I. Solvent Red 8, 12715 [33270-70-1] (1). 

Ligand incorporation was achieved by facile alkoxylation of 4-chloro-substituted ter-pyridine by a hydroxy-terminated carboxylic acid followed by divergent dendrimer con-... 

Chloro-7-methyl-1 H-indazol-3 -yl) -5 -pyridin-3 -yl-thiazole-4-carboxylic acid [3-(5-oxo-4,5-dihydro-lH-pyrazol-4-yl)-propyl]-amide aOJ tQTn o Y-O HN 7 H N... 

Alkylpyrazines with other substituents have been oxidized to carboxylic acids as follows 2-acetamido-6-methylpyrazine was oxidized in aqueous magnesium sulfate with potassium permanganate to 2-acetamido-6aqueous potassium permanganate at room temperature to 2-carboxy-3-chloropyrazine, which was also obtained by oxidation of 2-chloro-3-methylpyrazine with selenium dioxide in boiling aqueous pyridine (947). Oxidations of 2-methoxy-3-methyl-... 

Polymer-bound reagents have also been used. The synthetically important Weinreb amides [RCON(Me)OMe, see 16-82] can be prepared from the carboxylic acid and MeO(Me)NH HCl in the presence of tributylphosphine and 2-pyridine-A -oxide disulfide. Di(2-pyridyl)carbonate has been used in a related reaction that generates amides directly. The reaction of a carboxylic acid and imidazole under microwave irradiation gives the amide. Microwave irradiation of a secondary amine, formic acid, 2-chloro-4,6-dimethoxy[l,3,5]tria-zine, and a catalytic amount of DMAP (4-dimethylaminopyridine) leads to the formamide. ° Ammonium bicarbonate and formamide converts acids to amides with microwave irradiation. Lactams are readily produced from y- or 8-amino acids, for example. 

The formation of alcohols or ethers is favored by low current densities, porous graphite as anode material, a solvent such as water/pyridine instead of methanol, a pH of the electrolyte above 7 and anions, such as bicarbonate, sulfate or perchlorate, as additives. Electron-donating substituents at C-2 of the carboxylic acid favor the oxidation of the intermediate radical. Thus a-alkyl, a-cycloal-kyl207,208 a-chloro, a-bromo, a-amino, a-alkoxy, a-hydroxy, a-acyloxy and a,a-diphenyl substituents more or less promote the formation of nonKolbe products. 

The reaction of elemental sulfur in pyridine with 1,2-dithiolylium salts has been used for the synthesis of several l,2-dithiole-3-thiones.7 3-Chloro-1,2-dithiolylium salts give l,2-dithiole-3-thiones with sulfur-free bases such as ethanol, ammonia, methyl- and dimethylamine, piperidine, morpholine, and the azide ion.8 These salts form l,2-dithiol-3-ones with carboxylic acids.8... 

Pyrazolo[3,4-Z)]pyridines, the 7-chloro-6-fluoro-2,4-dimethylquinoline and its mercapto-thiadiazolyl or oxadiazolyl quinolines 21 were prepared via Diels-Alder reaction conversion of methyl 2-(3-oxo-3-phenylpropenylamino)benzoate into 3-benzoyl-l.S -quinolin-4-one 22 . A mixture of aniline derivatives and malonic ester gave a variety of 3-aryl-4-hydroxyquinolin-2(l//)-ones 23. Condensation of isatins with ketones afforded quinoline-4-carboxylic acids. 2-Aryl-l,2,3,4-tetrahydro-4-quinolinones 22 and carbazolylquinolone were also prepared. The substitution of 2-chloroquinoline gave the 2-substituted quinolines. Basic alumina has catalyzed the C-C bond formation between 2-hydroxy-1,4-naphthoquinone and 2-chloroquinoline derivative to give 21. Reaction of organic halides with 8-hydroxyquinolines gave the respective ethers. The azodye derivatives of 21 were prepared in the absence of solvent. Silica gel catalyzed the formation of 2-ketomethylquinolines from reaction of 2-methylquinolines with acyl chlorides. 

Pyridine-N-oxide [1, 966]. a-Bromo and a-chloro carboxylic acids are oxidatively decarboxylated by treatment with pyridine-N-oxide (4 equiv.) in refluxing benzene or toluene.3 Cohen et at. note that, since pivalic acid is completely inert to pyridine-N-oxide, an u-hydrogen atom appears to be essential, for example in the reaction of phenylacetic acid. They suggest that an a-pyridinium ion is an intermediate ... 

Attempts to condense the quinolizine (73.4) with methyl propynoate in boiling tenzene or toluene containing palladium-charcoal failed, but when nitrobenzene was used, moderate-to-good yields of the pyridoquinolizine were obtained. Formation of a 4 oxo- or 4-chloro-pyridine ring from a carboxylic acid (or ester) or an acyl chloride respectively Is well documented (see pp. 378-381, and Section II.3 of this chapter) in this particular example, a fused... 

A differently anchored Mukaiyama reagent is the N-methylpyridinium iodide salt 57 [71], which has been obtained by reaction of the Merrifield resin with N-Boc-aminocaproic acid in the presence of cesium carbonate to give the supported ester 55 (Scheme 7.19). Further Boc-deprotection and reaction with 6-chloronicoti-noyl chloride in the presence of Hxinig s base furnished the anchored 2-chloro-pyridine 56, which was transformed into the final N-methylpyridinium salt 57 after N-methylation in neat methyl iodide. This supported reagent has been used in the rapid microwave-assisted esterification of carboxylic acids and alcohols in the presence of triethylamine as base, with dichloromethane as solvent at 80 °C, the products being obtained in high purity after simple resin filtration [72],... 

Kamochi and Kudo have reported the use of the Sml2/THF-H20 system to reduce aromatic carboxylic acids to alcohols (Scheme 50). Furthermore, aromatic esters amides and nitriles were similarly reduced by this system in good yield [104]. As indicated above, reduction of carboxylic acids to primary alcohols is also effective with Sml2 in a THF-H20-NaOH mixture [105]. In contrast, without water these substrates remain unchanged. With the Sml2/THF-H20 system, pyridine was rapidly reduced to piperidine in similar reactions with pyridine derivatives bearing chloro, amino and cyano substituents, these functionalities were partly eliminated to afford pyridine or piperidine [107]. 

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