Carboxylic Acids and Derivatives to Alcohols

A solution of the methyl ester (3.35 g, 14.0 mmol) in dry THF (50 mL) was added dropwise to a slurry of LAH (0.797 g, 21.0 mmol) in dry THF at 0 °C under a nitrogen atmosphere. When the addition was complete, the cooling bath was removed and the mixture was stirred at ambient temperature. After 16 h, thin layer chromatography (TLC 2 1 hexanes/EtOAc) revealed that the reaction was complete. The mixture was 

Alane must be prepared in situ. It is an excellent reagent for the 1,2-reduction of a,p-unsaturated esters. It selectively reduces esters in the presence of halogens and nitro groups. Reviews (a) Seyden-Penne, J. Reductions by the Alumino- and Borohydrides in Organic Synthesis Wiley-VCH New York, 1997, 2nd edition, (b) Brown, H. C. Krishnamurthy, S. Tetrahedron 1979, 35, 567-607. 

To a suspension of LAH (0.60 g, 16 mmol) in dry ether (50 mL) at 0 °C was added a solution of aluminum trichloride (3.2 g, 24 mmol) in dry ether (40 mL) over a period of 10 min. The above mixture was stirred for 30 min, and the solution of the a, 3-unsaturated ester (3.7 g, 16 mmol) in dry ether (25 mL) was added over a period of 10 min at 0 °C and stirred at the same temperature for 1 h. The reaction mixture was diluted with ether (100 mL), and small ice pieces were added carefully. The solid formed was filtered, and the filtrate was evaporated to afford 3.12 g (93%) of the allylic alcohol as a viscous liquid. 

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This reagent also reduces nitro, nitrile, and amide derivatives to amines, and carboxylic acids and anhydrides to alcohols. The yields of these reductions arc nearly quantitative. Esters and halobenzene derivatives are not reduced. 

The next several chapters deal with the chemistry of various oxygen containing func tional groups The interplay of these important classes of compounds—alcohols ethers aldehydes ketones carboxylic acids and derivatives of carboxylic acids— IS fundamental to organic chemistry and biochemistry... 

Reactions of 1,2-diaminoalkenes with alcohols, aldehydes, or carboxylic acids and derivatives at high temperatures in the presence of a dehydrogenating agent are common approaches to the synthesis of 2-substituted imidazoles (89KFZ1246). In the absence of the dehydrogenating agent the products are imidazolines. 

The heterobimetallic complexes [N(n-Bu)4] [Os(N)R2(/u.-0)2Cr02] catalyze the selective oxidation of alcohols with molecular oxygen. A mechanism in which alcohol coordinates to the osmium center and is oxidized by B-hydrogen elimination (see -Hydride Elimination) is consistent with the data. The hydroxide adduct of OSO4, [0s(0H)204], with ferric cyanide and other co-oxidants catalyzes the oxidative dehydrogenation of primary aromatic and aliphatic amines to nitriles, the oxidation of primary alcohols to carboxylic acids, and of secondary alcohols to ketones. Osmium derivatives such as OsCb catalyze the effective oxidation of saturated hydrocarbons in acetonitrile through a radical mechanism. ... 

Carboxylic acids and derivatives. A particularly striking property of lithium aluminum hydride is its ability to reduce carboxylic acids to primary alcohols. Displacement of the acidic hydrogen uses up j mole of the reagent and i mole more is required for the reduction. Thus good yields are obtained with 0.75 mole of hydride per mule of acid." Triphenylucetic acid is not reduced under ordinary conditions... 

Esters derived from small- to medium-chain carboxylic acids and small- to medium-chain alcohols are the so-called fruit ethers. These are present in fruits and ethereal oils and are characterised by their pleasant aromas. A large variety of synthetic aromatic principles for use in the perfume industry can be synthesised from suitable carboxylic acids and alcohols. 

Reactivity of various carboxyl derivatives decreases in the order, acid chlorides > (aldehydes, ketones) > anhydrides > esters > carboxylic acids > amides. Carboxylic acids are reduced to alcohols under vigorous conditions. High P (35 X 10 to 70 X 10 kPa) and elevated T (up to 230°C) are required to effect conversion in high yields. 

This derivative is prepared from an A-protected amino acid and the anthrylmethyl alcohol in the presence of DCC/hydroxybenzotriazole. It can also be prepared from 2-(bromomethyl)-9,10-anthraquinone (Cs2C03). It is stable to moderately acidic conditions (e.g., CF3COOH, 20°, 1 h HBr/HOAc, / 2 = 65 h HCl/ CH2CI2, 20°, 1 h). Cleavage is effected by reduction of the quinone to the hy-droquinone i in the latter, electron release from the —OH group of the hydroqui-none results in facile cleavage of the methylene-carboxylate bond. The related 2-phenyl-2-(9,10-dioxo)anthrylmethyl ester has also been prepared, but is cleaved by electrolysis (—0.9 V, DMF, 0.1 M LiC104, 80% yield). ... 

These formulae explain the scission products of the two alkaloids and the conversion of evodiamine into rutaecarpine, and were accepted by Asahina. A partial synthesis of rutaecarpine was effected by Asahina, Irie and Ohta, who prepared the o-nitrobenzoyl derivative of 3-)3-amino-ethylindole-2-carboxylic acid, and reduced this to the corresponding amine (partial formula I), which on warming with phosphorus oxychloride in carbon tetrachloride solution furnished rutaecarpine. This synthesis was completed in 1928 by the same authors by the preparation of 3-)S-amino-ethylindole-2-carboxylic acid by the action of alcoholic potassium hydroxide on 2-keto-2 3 4 5-tetrahydro-3-carboline. An equally simple synthesis was effected almost simultaneously by Asahina, Manske and Robinson, who condensed methyl anthranilate with 2-keto-2 3 4 5-tetrahydro-3-carboline (for notation, see p. 492) by the use of phosphorus trichloride (see partial formulae II). Ohta has also synthesised rutaecarpine by heating a mixture of 2-keto-2 3 4 5-tetrahydrocarboline with isatoic anhydride at 195° for 20 minutes. 

Pentafluorobenzyl bromide has been used in the derivatization of mercaptans [55] and phenols [36], m the analysis of prostaglandins [37], and in quantitative GC-MS [5S] 1,3 Dichlorotetrafluoroacetone is used for the derivatization of amino acids to the corresponding cyclic oxazolidinones and allows the rapid analysis of all 20 protein ammo acids [d] Pentafluorophenyldialkylchlorosilane derivatives have facilitated the gas chromatographic analysis of a wide range of functionally substituted organic compounds, including steroids, alcohols, phenols, amines, carboxylic acids, and chlorohydrms [4]... 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

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