5-«-butyl-2-carboxylic acid,

The conversion of primary alcohols and aldehydes into carboxylic acids is generally possible with all strong oxidants. Silver(II) oxide in THF/water is particularly useful as a neutral oxidant (E.J. Corey, 1968 A). The direct conversion of primary alcohols into carboxylic esters is achieved with MnOj in the presence of hydrogen cyanide and alcohols (E.J. Corey, 1968 A,D). The remarkably smooth oxidation of ethers to esters by ruthenium tetroxide has been employed quite often (D.G. Lee, 1973). Dibutyl ether affords butyl butanoate, and tetra-hydrofuran yields butyrolactone almost quantitatively. More complex educts also give acceptable yields (M.E. Wolff, 1963). 

J-unsaturated ester is formed from a terminal alkyne by the reaction of alkyl formate and oxalate. The linear a, /J-unsaturated ester 5 is obtained from the terminal alkyne using dppb as a ligand by the reaction of alkyl formate under CO pressure. On the other hand, a branehed ester, t-butyl atropate (6), is obtained exclusively by the carbonylation of phenylacetylene in t-BuOH even by using dppb[10]. Reaction of alkynes and oxalate under CO pressure also gives linear a, /J-unsaturated esters 7 and dialkynes. The use of dppb is essen-tial[l 1]. Carbonylation of 1-octyne in the presence of oxalic acid or formic acid using PhiP-dppb (2 I) and Pd on carbon affords the branched q, /J-unsatu-rated acid 8 as the main product. Formic acid is regarded as a source of H and OH in the carboxylic acids[l2]. 

Phthalocyanine sulfonic acids, which can be used as direct cotton dyes (1), are obtained by heating the metal phthalocyanines in oleum. One to four sulfo groups can be introduced in the 4-position by varying concentration, temperature, and reaction time (103). Sulfonyl chlorides, which are important intermediates, can be prepared from chlorosulfonic acid and phthalocyanines (104). The positions of the sulfonyl chloride groups are the same as those of the sulfonic acids (103). Other derivatives, eg, chlormethylphthalocyanines (105—107), / /f-butyl (108—111), amino (112), ethers (109,110,113—116), thioethers (117,118), carboxyl acids (119—122), esters (123), cyanides (112,124—127), and nitrocompounds (126), can be synthesized. 

In some instances a carbon-carbon bond can be formed with C-nucleophiles. For example, 3-carboxamido-6-methylpyridazine is produced from 3-iodo-6-methylpyridazine by treatment with potassium cyanide in aqueous ethanol and l,3-dimethyl-6-oxo-l,6-dihydro-pyridazine-4-carboxylic acid from 4-chloro-l,3-dimethylpyridazin-6-(lH)-one by reaction with a mixture of cuprous chloride and potassium cyanide. Chloro-substituted pyridazines react with Grignard reagents. For example, 3,4,6-trichloropyridazine reacts with f-butyl-magnesium chloride to give 4-t-butyl-3,5,6-trichloro-l,4-dihydropyridazine (120) and 4,5-di-t-butyl-3,6-dichloro-l,4-dihydropyridazine (121) and both are converted into 4-t-butyl-3,6-dichloropyridazine (122 Scheme 38). 

Potassium t-butoxide in t-butyl alcohol requires powerful electron-attracting substituents at C-4 to effect ring opening of pyrazoles but sodamide does not (Scheme 26) (B-76MI40402). As the key to the transformation is the generation of the anion, similar results were obtained by heating some pyrazole-3-carboxylic acids with quinoline. 

Thiacyclotrideca-2,4,10,12-tetraene-6,8-diyne 1 -oxide, 5,10-dimethyl- HNMR, 7, 717 (75JA640) 4-Thia-2,6-diazabicyclo[3.2.0]heptane-2-carboxylic acid, 7-OXO-, t-butyl ester X-ray, 7, 349 (B-72M151201) 5H-2aA -Thia-2,3-diazacyclopent[cd]indene, 2,3-dimethyl-6,7-dihydro-X-ray, 6, 1054 (72ACS343)... 

Azetidine, 7V-bromo-, 7, 240 Azetidine, AT-r-butyl- N NMR, 7, 11 Azetidine, AT-t-butyl-3-chloro-transannular nucleophilic attack, 7, 25 Azetidine, 3-chloro-isomerization, 7, 42 Azetidine, AT-chloro-, 7, 240 dehydrohalogenation, 7, 275 Azetidine, 7V-chloro-2-methyl-inversion, 7, 7 Azetidine, 3-halo-synthesis, 7, 246 Azetidine, AT-halo-synthesis, 7, 246 Azetidine, AT-hydroxy-synthesis, 7, 271 Azetidine, 2-imino-stability, 7, 256 Azetidine, 2-methoxy-synthesis, 7, 246 Azetidine, 2-methyl-circular dichroism, 7, 239 optical rotatory dispersion, 7, 239 Azetidine, AT-nitroso-deoxygenation, 7, 241 oxidation, 7, 240 synthesis, 7, 246 Azetidine, thioacyl-ring expansion, 7, 241 Azetidine-4-carboxylic acid, 2-oxo-oxidative decarboxylation, 7, 251 Azetidine-2-carboxylic acids absolute configuration, 7, 239 azetidin-2-ones from, 7, 263 synthesis, 7, 246... 

Benzo[b]thiophene-2-carboxylic acid, 3-t-butyl-nitration, 4, 763... 

Pyrazine, tetrahydro-, 3, 177, 178 Pyrazine, 1,2,3,4-tetrahydro-synthesis, 3, 177 Pyrazine, 2,3,5-tri-t-butyl-synthesis, 3, 185 Pyrazine, 2,3,5-trichloro-nucleophilic substitution, 3, 176 Pyrazine, 2-vinyl-polymers, 1, 290-291 Pyrazine-3-carboxylic acid, 2-amino-methyl ester... 

Isobutylene, cat. coned. H2SO4, CH Cl, 25°, 6-10 h, 93% yield. These conditions also convert carboxylic acids to /-butyl esters. 

The dibenzosuberyl ester is prepared from dibenzosubeiyl chloride (which is also used to protect —OH, —NH, and —SH groups) and a carboxylic acid (Et N, reflux, 4 h, 45% yield). It can be cleaved by hydrogenolysis and, like t-butyl esters, by acidic hydrolysis (aq. HCl/THF, 20°, 30 min, 98% yield). ... 

The change of mechanism with tertiary alkyl esters is valuable in synthetic methodology because it permits certain esters to be hydrolyzed very selectively. The usual situation involves the use of t-butyl esters, which can be cleaved to carboxylic acids by action of acids such as p-toluenesulfonic acid or trifluoroacetic acid under anhydrous conditions where other esters are stable. 

Plasticizers can be classified according to their chemical nature. The most important classes of plasticizers used in rubber adhesives are phthalates, polymeric plasticizers, and esters. The group phthalate plasticizers constitutes the biggest and most widely used plasticizers. The linear alkyl phthalates impart improved low-temperature performance and have reduced volatility. Most of the polymeric plasticizers are saturated polyesters obtained by reaction of a diol with a dicarboxylic acid. The most common diols are propanediol, 1,3- and 1,4-butanediol, and 1,6-hexanediol. Adipic, phthalic and sebacic acids are common carboxylic acids used in the manufacture of polymeric plasticizers. Some poly-hydroxybutyrates are used in rubber adhesive formulations. Both the molecular weight and the chemical nature determine the performance of the polymeric plasticizers. Increasing the molecular weight reduces the volatility of the plasticizer but reduces the plasticizing efficiency and low-temperature properties. Typical esters used as plasticizers are n-butyl acetate and cellulose acetobutyrate. 

The nature of the base, CmHijN, varies. When produced from pure Mupinine, m.p. 68-9°, it furnishes on oxidation only 3-methylpyridine-2-carboxylic acid (XV) and pyridine-2 3-dicarboxylic acid. If, however, lupinine, m.p. 63-3°, is used, the resulting pyridine base on oxidation furnishes in addition 2-n-butylpyridine-6-carboxylic acid (XVI) and 6-methylpyridine-2-carboxylic acid (XVII). The conclusion is drawn that lupinine, m.p. 63-3°, is a mixture of 1-lupinine (XI) with aZlolupinine (XII), each of these components furnishing its own lupinane (XIII and XIV), and that these two lupinanes contribute to the final degradation product, the tertiary pyridine base, CioHuN, the two isomerides 2-w-Ijutyl-3-inethylpyridine (XVIII) and 2-w-butyl-6-raethylpyridine (XIX) respectively. These interrelationships are shown by the following scheme —... 

Me3SiCH2CH=CH2, TsOH, CH3CN, 70-80°, 1-2 h, 90-95% yield. " This silylating reagent is stable to moisture. Allylsilanes can be used to protect alcohols, phenols, and carboxylic acids there is no reaction with thio-phenol, except when Cp3S03H is used as a catalyst. The method is also applicable to the formation of r-butyldimethylsilyl derivatives the silyl ether of cyclohexanol was prepared in 95% yield from allyl-r-butyl-dimethylsilane. Iodine, bromine, trimethylsilyl bromide, and trimethylsilyl iodide have also been used as catalysts. Nafion-H has been shown to be an effective catalyst. ... 

Acidic and basic hydrolysis of ethyl 4-oxo-4//-pyrido[l, 2-u]pyrimidin-3-carboxylates gave 3-carboxylic acid derivatives (OlMIPl). Stirring rerr-butyl ( )-3-(2-hydroxy-8-[2-(4-isopropyl-l, 3-thiazol-2-yl)-l-ethenyl]-4-oxo-4//-pyrido[l,2-u]pyrimidin-3-yl)-2-propenoate in CF3CO2H at room temperature yielded ( )-3-substituted 2-propenoic acid. 

A setup similar to the preceding one is used in this experiment except that provision should be made for heating the reaction vessel (steam bath, oil bath, or mantle). Lithium aluminum hydride (10 g, 0.26 mole) is dissolved in 200 ml of dry -butyl ether and heated with stirring to 100°. A solution of 9.1 g (0.05 mole) of ra j-9-decalin-carboxylic acid (Chapter 16, Section I) in 100 ml of dry -butyl ether is added dropwise over about 30 minutes. The stirring and heating are continued for 4 days, after which the mixture is cooled and water is slowly added to decompose excess hydride. Dilute hydrochloric acid is added to dissolve the salts, and the ether layer is separated, washed with bicarbonate solution then water, and dried. The solvent is removed by distillation, and the residue is recrystallized from aqueous ethanol, mp 77-78°, yield 80-95 %. 

Esters can also be synthesized by an acid-catalyzed nucleophilic acyl substitution reaction of a carboxylic acid with an alcohol, a process called the Fischer esterification reaction. Unfortunately, the need to use an excess of a liquid alcohol as solvent effectively limits the method to the synthesis of methyl, ethyl, propyl, and butyl esters. 

If the reaction just described is conducted in the presence of a suitable hydrogen atom donor such as tri-n-butyltin hydride or tert-butyl hydrosulfide, reductive decarboxylation occurs via a radical chain mechanism to give an alkane (see 125—>128, Scheme 24). Carboxylic acids can thus be decarboxylated through the intermediacy of their corresponding thiohydroxamate esters in two easily executed steps. In this reducjtive process, one carbon atom, the carbonyl carbon, is smoothly excised... 

In another approach, a glucose-derived titanium enolate is used in order to accomplish stereoselective aldol additions. Again the chiral information lies in the metallic portion of the enolate. Thus, the lithiated /m-butyl acetate is transmetalated with chloro(cyclopentadienyl)bis(l,2 5,6-di-0-isopropylidene- -D-glucofuranos-3-0-yl)titanium (see Section I.3.4.2.2.I. and 1.3.4.2.2.2.). The titanium enolate 5 is reacted in situ with aldehydes to provide, after hydrolysis, /i-hydroxy-carboxylic acids with 90 95% ee and the chiral auxiliary reagent can be recovered76. 

Methyl esters of aliphatic dibasic carboxylic acids (-CH2C(0)0CH3) n-Butyl esters (loss of 04H9O)t... 

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