CeCl3-Catalyzed Reduction of Methyl Esters of Carboxylic Acids to Corresponding Alcohols with Sodium Borohydride

A wide range of methyl esters, including esters of aromatic carboxylic acids, alkenyl carboxylic acids, aliphatic carboxylic acids, and protected amino acids, were reduced to the corresponding alcohols with NaBH₄ in ethanol in the presence of a catalytic amount of CeCl₃. The reaction was completed within 24 h at ambient temperature and showed high functional group compatibility and chemoselectivity. With esters containing nitro, methoxyl, halogen, alkenyl, and protected amino functionalities, only the ester group was reduced. The alcohols were isolated after evaporation of the solvent and routine aqueous workup in good yields (75–95%).     

Sodium borohydride reduction of aromatic carboxylic acids via methyl esters

A number of important aromatic carboxylic acids precursors, or intermediates in the syntheses of natural products, are converted into methyl esters and reduced to the corresponding primary alcohols using a sodium borohydride-THF-methanol system. The alcohols are obtained in 70–92% yields in 2–5 hours, in a pure state. This two-step procedure not only provides a better alternative to aluminum hydride reduction of acids but also allows the selective reduction of esters in presence of acids, amides, nitriles or nitro functions which are not affected under these conditions.     

Divergent pathway for the solid-phase conversion of aromatic acetylenes to carboxylic acids, alpha-ketocarboxylic acids, and methyl ketones

An efficient divergent pathway for the selective and quantitative solid-phase conversion of aromatic acetylenes to the corresponding carboxylic acids, alpha-keto-carboxylic acids, and methyl ketones is presented. A range of aromatic trimethylsilyl-protected acetylene building blocks was synthesized in excellent yields using a Sonogashira cross-coupling protocol and used in solid-phase synthesis on PEGA resin. Dependent on the selection of conditions, the same solid-supported alkyne could be quantitatively converted to an aromatic carboxylic acid, an aromatic alpha-ketocarboxylic acid, or an aromatic methyl ketone. The conversion to carboxylic acid involved an OsO4/NaIO4/HMTA-mediated oxidative cleavage of the silyl-deprotected alkyne to provide the aromatic carboxylate in excellent yield. The alpha-ketocarboxylic acids were obtained by direct treatment of the trimethylsilyl-protected alkyne with OsO4/NMO/HMTA, while the ketones were obtained by simple acid-mediated hydration of the alkyne using aqueous TFA. In general, all products were obtained in excellent purities, typically above 90%. In addition, it was shown that the alkyne-containing building blocks could easily be incorporated into resin-bound peptides and after chemoselective conversion of the alkyne the new functional groups could be used for further derivatization into peptidomimetic compounds.     

A highly convenient,efficient, and selective process for preparation of esters and amides from carboxylic acids using Fe(3+)-K-10 montmorillonite clay

In the presence of Fe(3+)-K-10 montmorillonite clay as a catalyst, aliphatic carboxylic acids selectively produced the corresponding esters in the presence of aromatic carboxylic acids by treatment with alcohols. Both the aliphatic and aromatic carboxylic acids formed the amides by reacting with the aliphatic amines, but only the aliphatic carboxylic acids yielded the anilides by treatment with aromatic amines. The catalyst is recoverable and recyclable.     

One-Pot Reduction of Carboxylic Acids via O-Acylisoureas

A simple one-pot reduction of aliphatic carboxylic acids to primary alcohols, by treatment with dicyclohexylcarbodiimide followed by lithium borohydride, is reported. The same methodology applied to aromatic carboxylic acids is shown to give a mixture of the alcohols with N-cyclohexylcarboxamides.     

Enantiomeric separation of alcohols and amines on a proline chiral stationary phase by gas chromatography

A new chiral stationary phase for gas chromatography was prepared by covalently attaching a diproline chiral selector that has proven to be effective in liquid chromatography to a methylhydrosiloxane-dimethylsiloxane copolymer. With this new chiral stationary phase for GC, racemic aromatic alcohols could be resolved without derivatization. Racemic aromatic and aliphatic amines could also be resolved after derivatization of the amino groups with trifluoroacetic anhydride or isopropyl isocyanate. On this stationary phase, the isopropyl isocyanate derivatives of amines showed higher enantioselectivity than the trifluoroacetic anhydride derivatives. In both the enantiomeric separations of alcohols and derivatized amines, the aromatic racemic analytes showed higher enantioselectivities than their aliphatic analogs. Some of the alpha-amino and alpha-hydroxy aromatic acids could also be separated after derivatization to N-trifluoroacetyl methyl esters for amino acids or O-trifluoroacetyl methyl esters for hydroxyl acids.     

无溶剂条件下锰 (Ⅲ)-席夫碱配合物催化过氧化氢氧化醇

 Aliphatic and aromatic alcohols are efficiently oxidized to ketones or carboxylic acids using aqueous hydrogen peroxide as an oxidant in the presence of a Mn(III) Schiff-base complex as a catalyst under solvent-free conditions. The oxidation of alcohols occurred at 50 °C to give the corresponding ketones or carboxylic acids with a yield higher than 60%.     

A direct reduction of aliphatic aldehyde, acyl chloride, ester, and carboxylic functions into a methyl group

The aliphatic carboxylic group was efficiently reduced to the methyl group by HSiEt(3) in the presence of catalytic amounts of B(C(6)F(5))(3). To the best of our knowledge, this is the first example of a direct exhaustive reduction of aliphatic carboxylic function. Aliphatic aldehydes, acyl chlorides, anhydrides, and esters also underwent complete reduction under similar reaction conditions. Aromatic carboxylic acids, as well as other carbonyl functional equivalents, underwent smooth partial reduction to the corresponding TES-protected benzylic alcohols. It was shown that, unlike the reduction of aliphatic substrates, the exhaustive reduction of aromatic substrates was not straightforward: a concurrent Friedel-Crafts-like alkylation process competed with the reduction yielding trace to notable amounts of dimeric products, thus decreasing the overall selectivity of the reduction process.     

Effective esterification of carboxylic acids using (6-oxo-6H-pyridazin-1-yl)phosphoric acid diethyl ester as novel coupling agents

(6-Oxo-6H-pyridazin-1-yl)phosphoric acid diethyl esters (3) are efficient and selective coupling agents for equimolar esterification of carboxylic acids and alcohols. Esterification of aliphatic and aromatic carboxylic acids with aliphatic and aromatic alcohols using 3 afforded the corresponding esters chemoselectively in good to excellent yield.     

高分子载体Lewis酸催化剂聚苯乙烯-四氯化钛复合物

交联聚苯乙烯白球(含DVB 5～7%)在CS₂中与TiCl₄反应可形成一种稳定的复合物,其含氯量为4.5%。这种复合物不怕水,在空气中放置一年以上不失效。这种高分子载体Lewis酸催化剂可作为酯化、缩醛、缩酮、成醚和付氏烷基化等有机合成反应的良好催化剂,还可重复使用4—5次。     

Solvent-modulated chemoselective deprotections of trialkylsilyl esters and chemoselective esterifications

A series of trialkylsilyl esters were deprotected or transesterificated into their corresponding carboxylic acids or methyl esters under a catalytic amount of CBr₄ in alcohol reaction system. This method enables to desilylate secondary sp³-carbon, sp²-carbon, sp-carbon and aryl tethered trialkylsilyl esters to carboxylic acids, whereas primary sp³-carbon tethered trialkylsilyl esters were further converted into their methyl esters under CBr₄/MeOH reaction conditions. The highly chemoselective deprotections can be modulated and achieved by the introduced protecting trialkylsilyl groups and the used alcohols such as MeOH and EtOH under this photochemically-induced reaction conditions.     

Copper(II) triflate-catalyzed reduction of carboxylic acids to alcohols and reductive etherification of carbonyl compounds

A protocol is described for the reduction of carboxylic acids to primary alcohols using 1,1,3,3-tetramethyldisiloxane (TMDS) and a catalytic amount of Cu(OTf)₂. Aliphatic as well as aromatic carboxylic acids are reduced in high selectivity and good yields. TMDS/Cu(OTf)₂ has also been found to be an efficient catalytic reducing system for the preparation of symmetrical ethers from carbonyl compounds under mild conditions.     

Esterification and Selective Esterification in the Presence of TiCl4

A series of carboxylic acids was esterified to the corresponding esters with TiCl_4 as catalyst at room temperature,in high yields.This catalyst was highly effective for the selective esterification of primary alcohols with carboxylic acids,in the presence of secondary alcohols,and for the selective esterification of saturated acid with alcohol in the presence of conjugated acid or aromatic acid.On account of the high yield,high chemoselectivity,mild condition,and being free of other dehydrants,this is an efficient method.     

Synthesis of Esters in the Presence of Chlorosilanes

Esterification of various carboxylic acids with primary alcohols in the presence of chloro(methyl)-silanes provides a simple and convenient synthetic route to esters.     

GC—MS analysis of carboxylic acids in petroleum after esterification with fluoroalcohols

The GC–MS characteristics of carboxylic acid esters prepared from fluorine-containing alcohols were compared to those of methyl esters. The GC retention of 2,2,2-trifluoroethyl (TFE) esters was less than, and 2,2,3,3,4,4,4-heptafluoro-1-butyl (HFB) esters was approximately equivalent to that of methyl esters. Mass spectra of TFE and HFB aliphatic esters show significantly more intense molecular and key fragment ions than those of methyl esters. Also, owing to their significantly higher molecular weights, TFE or HFB ester molecular ions and most fragment ions of interest occur at significantly higher m/z values than most potential interfering ions. Data for about 70 individual TFE and HFB esters are reported. Application of the methodology to a petroleum-derived carboxylic acid concentrate resulted in identification of straight chain, isoprenoid, methyl-substituted straight chain (2-, 3-, 5-,10-, 12-positions along chain), and dimethyl-substituted straight chain acids containing from 11 to 22 carbons. Benzoic acid and homologs with up to 3-carbons in alkyl substitutents were minor components in the sample. The procedure provided for forming TFE and HFB esters from free acids requires less time and effort than a previously reported method, while retaining its capability for achieving essentially quantitative conversion. Free hydroxyl groups in alcohols and phenols are converted to trifluoroacetate esters concurrently with formation of TFE/HFB carboxylic acid esters. The reaction products, including compounds with two functional groups (diacids, salicylic acid, etc.), chromatograph well on conventional nonpolar GC stationary phases.     

Methylation of Aliphatic and Aromatic Carboxylic Acids with Dimethyl Carbonate under the Influence of Manganese and Iron Carbonyls

The synthesis of methyl esters has been carried out via the reaction of aliphatic and aromatic carboxylic acids with dimethyl carbonate in the presence of manganese and iron carbonyls. The optimal ratio of catalyst and reagents and other conditions for the synthesis of methyl esters of carboxylic acids with high yield have been found.     

Novel polymers with a high carboxylic acid loading

Click chemistry has been used to prepare a range of novel polymers with pendant carboxylic acid side groups. Four azido carboxylic acids, either mono‐ or difunctional and aliphatic or aromatic, have been prepared and thoroughly characterized. Extensive model reactions with 1‐ethyl‐4‐hydroxybenzene, the simplest model for poly(4‐hydroxystyrene), and the four azido carboxylic acids have been conducted to establish the proper reaction conditions and provide an analytical frame for the corresponding polymers. Poly(4‐hydroxystyrene) moieties in three different polymers—poly(4‐hydroxystyrene), poly(4‐hydroxystyrene‐co‐methyl methacrylate), and poly(4‐hydroxystyrene‐b‐styrene)—have been quantitatively transformed into oxypropynes by the use of either Williamson or Mitsunobu strategies and subsequently reacted with the azido carboxylic acids. Detailed differential scanning calorimetry investigations of all the polymers in general exhibit [when poly(4‐hydroxystyrene) is a substantial part] significant changes in the glass‐transition temperature from the polar poly(4‐hydroxystyrene) (120–130 °C) to the much less polar alkyne polymers (46–60 °C). A direct correlation between the nature of the pendant groups in the derivatized polymers and the glass‐transition temperature has emerged: the aromatic carboxylic acids give high glass‐transition temperatures (90–120 °C), and the aliphatic carboxylic acids give lower glass‐transition temperatures (50–65 °C). © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44:6360–6377, 2006     

A facile method for oxidation of primary alcohols to carboxylic acids and its application in glycosaminoglycan syntheses

A convenient two-step, one-pot procedure was developed for the conversion of primary alcohols to carboxylic acids. The alcohol was first treated with NaOCl and TEMPO under phase-transfer conditions, followed by NaClO2 oxidation in one pot. This reaction is applicable to a wide range of alcohols and the mild reaction conditions are compatible with many sensitive functional groups, including electron-rich aromatic rings, acid-labile isopropylidene ketal and glycosidic linkages, and oxidation-prone thioacetal, p-methoxybenzyl, and allyl moieties. Several glycosaminoglycans such as heparin, chondroitin, and hyaluronic acid oligosaccharides have been synthesized in high yields by using this new oxidation protocol.     

Practical calculation of molecular acidity with the aid of a reference molecule

A set of linear free energy models are presented for determining the pK(a) values of amines, alcohols, and carboxylic acids. Models are determined from a series of pK(a) predictors, taken both from traditional natural atomic orbital analysis (NAO) and from a novel approach introduced here of using a reference molecule: an ammonium ion for amines and a hydrogen sulfide molecule for alcohols and carboxylic acids. Using these reference molecules, we calculate the barrier to proton transfer and show that a number of properties associated with the transition state are correlated with the pK(a). By considering 38 predictors, we obtain a four-variable model for amines and a three-variable model for oxygen-containing compounds. The model for amines is based on 145 compounds and has a root mean squared error (RMSE) of 0.45 and R(2) = 0.98. The oxygen set has 48 molecules: RMSE = 0.26, and R(2) = 0.993. Similar, linear, and multilinear models are constructed after separating the sets into chemically similar categories: alcohols, carboxylic acids, and primary, secondary, tertiary, and aromatic amines. This separation gives simpler models with relatively low RMSE values, where the most important predictor of the pK(a) is the difference in energy between transferring the proton from the reference molecular base to the conjugate acid from the data set.     

Characterization of the high molecular mass chlorinated matter in spent bleach liquors (SBL): 3—Mass spectrometric interpretation of aromatic degradation products in SBL

The aromatic content of the high molecular matter in pulp mill bleachery effluents has been characterized after chemical degradation in the laboratory followed by derivatization and gas chromatographic/mass spectrometric analysis. Aromatic molecules with carboxy, hydroxy, methoxy and chloro substituents were separated and identified by recording their computer-reconstructed ion current chromatograms. About 70 aromatic carboxylic acids were tentatively identified as degradation products. Aromatic compounds with hydroxy groups were derivatized to trideuteromethoxy groups in order to distinguish them by mass spectrometry from compounds with naturally occurring methoxy groups. Single and double hydrogen atom transfer between methyl ester and methoxy groups were observed in some molecules and given special attention when they occurred ortho to each other. A methoxy group substituted ortho to a methyl carboxylate resulted in an unusual fragmentation.