Reductic acids

Cr reduction, acid 1. Na2S20 2. SO2 3. FeSO -7H20 3.0-3.5 30 Ee " salts produce four times more sludge than Cr ... 

Nonaqueous Bases Nonaqueous Nucleophiles Organometallic Catalytic Reduction Acidic Reduction Basic or Neutral Reduction Hydride Reduction Lewis Acids Soft Acids Radical Addition Oxidizing Agents... 

Conversion of Acid Chlorides into Alcohols Reduction Acid chlorides are reduced by LiAJH4 to yield primary alcohols. The reaction is of little practical value, however, because the parent carboxylic acids are generally more readily available and can themselves be reduced by L1AIH4 to yield alcohols. Reduction occurs via a typical nucleophilic acyl substitution mechanism in which a hydride ion (H -) adds to the carbonyl group, yielding a tetrahedral intermediate that expels Cl-. The net effect is a substitution of -Cl by -H to yield an aldehyde, which is then immediately reduced by UAIH4 in a second step to yield the primary alcohol. 

COVALENT COMPOUNDS, METAL IONS OXIDATION-REDUCTION acid, viz. 

Scheme 9.1 shows several examples of one-carbon homologations involving boron to carbon migration. Entry 1 illustrates the synthesis of a symmetrical tertiary alcohol. Entry 2 involves interception of the intermediate after the first migration by reduction. Acid then induces a second migration. This sequence affords secondary alcohols. 

Typically, small molecule drugs are produced using reactions such as oxidation-reduction, acid-base, halogenation, alkylation, and substitution. 

Although small proportions of other products are formed when D-xylose is exposed to rather high acid concentrations, arabinose, lyxose, and ribose form considerably more of alternative products (generally reductic acid) than of 2-furaldehyde under these conditions. Reductic acid (2,3-dihydroxy-2-cyclopenten-l-one, 47) has been detected as a product after acid exposure of D-xylose or its major dehydration product, 2-furalde-hyde. Further work performed with D-[l- C]xylose and [a- C]2-fural-dehyde showed that reductic acid having identical label distribution was obtained from both starting materials. This indicated that a common primary source was involved, probably 2-furaldehyde, as it is readily formed from D-xylose under acidic conditions. 

Hexuronic acids are decarboxylated in the presence of refluxing, aqueous acid to form 5, reductic acid (2,3-dihydroxy-2-cyclopenten-l-one 47) and very small amounts of 48 (5-formyl-2-furoic acid). The yields of these products decrease when dilute acid solutions are used. Most of this work was performed with hydrochloric acid the use of phosphoric acid was not nearly so effective. For instance, D-galacturonic acid quantitatively lost CO2 within 4 h with 3.5 A/ HCl, whereas only 12 mole% of the CO2 was recovered after 4 h with 1.2 M H3PO4. The yields of CO2 from several hexuronic acids (including polygalacturonic acid) were comparatively determined. The acidic decarboxylation of hexuronic acids is bi-molecular and dependent on both the hexuronic acid and hydrochloric acid concentrations. Prior labeling work had established that C-6 of the hexuronic acid is the source of the CO2. 

In the majority of dehydration reactions, heterocyclic compounds are formed, rather than carbocyclic compounds. Many possibilities for formation of carbocyclic compounds exist, but these are important only if (a) the heterocyclic or acyclic tautomers cannot undergo further elimination reactions, or (b) the conditions of reaction greatly favor the formation of an acyclic tautomer capable of affording only the carbocyclic compound. Both five- and six-membered carbocyclic compounds have been isolated, with reductic acid being the compound most frequently reported. Ring closure occurs by an inter-molecular, aldol reaction that involves the carbonyl group and an enolic structure. Many examples of these aldol reactions that lead to formation of carbocyclic rings have been studied.47 As both elimination and addition of a proton are involved, the reaction occurs in both acidic and basic solutions. As examples of the facility of this reaction, pyruvic acid condenses spontaneously to a dibasic acid at room temperature in dilute solution, and such 8-diketones as 29 readily cyclize to form cyclohexenones, presumably by way of 30, either in acid or base. 

On treatment with aqueous mineral acid, L-ascorbic acid,90 hexu-ronic acids,91 and glycuronans92 undergo decarboxylation by which 1 mole of carbon dioxide per mole of acid is produced. For hexu-ronic acids, other detectable products include 2-furaldehyde (27) (Ref. 93), reductic acid (2,3-dihydroxy-2-cyclopenten-l-one, 75 see p. 207) (Refs. 53 and 94-96), and traces of 5-formyl-2-furoic acid... 

All of the possibilities mentioned are credible perhaps each participates to some extent in the reaction. No studies similar to those with aldoses have been made of substituted uronic acids, and no intermediates have been isolated. Aso,96 who first suggested 72 as a precursor for 2-furaldehyde and reductic acid,92 has prepared 72, but its significance in the decarboxylation reactions has not been fully examined.123... 

When treated with 5% sulfuric acid for 1.5 hours at 150°, pectin and D-galacturonic acid give reductic acid in yields of approximately 10% it is also formed on treatment of alginic acid with acid.96,119 The original preparation from pectin has been improved by using ion-exchange techniques,110 and synthetic preparations have been developed.188... 

Furaldehyde has also been reported as a source of reductic acid,189 and this has been verified.54 The yields are, however, less than 0.5%. D-Xylose also affords small proportions of reductic acid,54,94 but the yields are, apparently, much higher from the other pentoses when they are treated in concentrated sulfuric acid.52... 

Aso98 first proposed 5-hydroxy-2-oxo-3-pentenal (94) as an intermediate in the conversion of uronic acids to reductic acid,190 191 but this proposal does not appear to have been experimentally tested, although the intermediate was prepared.190 Isbell121 suggested a mechanism in which the formation of reductic acid and 2-furaldehyde from pentoses and uronic acids results from the reaction of different tautomers of 94. Although other mechanisms have been suggested,100 102 115 Isbell s original scheme seems adequate to explain the experimental facts. 

The formation of reductic acid and 2-furaldehyde from uronic acids is believed to occur through the same intermediate (72a) that is generated on decarboxylation of 3,4-dideoxy-D-g/t/cero-hex-3-enos-uluronic acid (71) (see Section III,3 p. 191). However, little is... 

Theander198 reported that treatment both of methyl /3-D-arabino-hexopyranosidulose and its related 3-ulose isomer (95a) with 0.25 M sulfuric acid for 2 hours at 100° gives large yields of reductic acid and... 

The absence of reductic acid from the reaction of D-arafotno-hexos-ulose (100) would indicate that the initial step in the reaction is the elimination of the hydroxyl group at C-4 (illustrated) or C-l, or dehydration through the acyclic form. The compounds resulting from... 

The occurrence of reductic acid among the acidic degradation products of oxidized cellulose197 can, perhaps, be explained by the presence of carbonyl groups at C-2 and C-3 in the polymer. 

D-Xylose was found to yield 2-furaldehyde almost exclusively, but D-lyxose, D-ribose, and L-arabinose produce another, as yet unidentified, compound absorbing at 289 nm, which is the maximum absorption wavelength for reductic acid. D-Glucose, D-fructose, and sucrose give almost identical yields (—85%) of 5-(hydroxymethyl)-2-fural-dehyde, but D-galactose and D-mannose give much lower yields thereof. 

In concentrated sulfuric acid, D-glucuronic acid is dehydrated more slowly than either its 4-O-methyl derivative or D-glucose, probably because of the stability of its lactone. All hexuronic acids, however, eventually produce the same characteristic absorbance that corresponds roughly to a composite of 5-formyl-2-furoic acid, 2-furaldehyde, and reductic acid. It is interesting that a thin-layer chromatographic examination of the reaction products of D-glucuronic acid with 89% sulfuric acid at 70° revealed 5-formyl-2-furoic acid as a major product, but no evidence was obtained for the presence of reductic acid. This result is in distinct contrast to the products obtained in dilute acid solutions, in which 5-formyl-2-furoic acid is produced in very low yield, whereas reductic acid is formed in yields in excess of 10%. 

Acid chlorides, R(Ar)COCl, are reduced to R(Ar)CHO by Hj/Pd(S), a moderate catalyst that does not reduce RCHO to RCHjOH (Rosenmund reduction). Acid chlorides, esters (R(Ar)COOR), and nitriles (RC N) are reduced with lithium tri-t-butoxyaluminum hydride, LiAlH[OC(CH3)3]j, at very low temperatures, followed by HjO. The net reaction is a displacement of X by H",... 

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