Carboxylic acids, with alcohols carbonyls

Mechanism of esterification of carboxylic acids The esterification of carboxylic acids with alcohols is a kind of nncleophilic acyl snbstitntion. Protonation of the carbonyl ojq gen activates the carbonyl gronp towards nncleophilic addition of the alcohol. Proton transfer in the tetrahedral intermediate converts the hydrojq l group into - 0H2 group, which, being a better leaving group, is eliminated as neutml water molecule. The protonated ester so formed finally loses a proton to give the ester. 

Perhaps the most valuable reaction of alcohols is their oxidation to yield car-bony compounds—the opposite of the reduction of carbonyl compounds to yield alcohols. Primary alcohols yield aldehydes or carboxylic acids, secondary alcohols yield ketones, but tertiary alcohols don t normally react with most oxidizing agents. 

When a carbonyl group is bonded to a substituent group that can potentially depart as a Lewis base, addition of a nucleophile to the carbonyl carbon leads to elimination and the regeneration of a carbon-oxygen double bond. Esters undergo hydrolysis with alkali hydroxides to form alkali metal salts of carboxylic acids and alcohols. Amides undergo hydrolysis with mineral acids to form carboxylic acids and amine salts. Carbamates undergo alkaline hydrolysis to form amines, carbon dioxide, and alcohols. 

Attempts to achieve selective oxidations of hydrocarbons or other compounds when the desired site of attack is remote from an activating functional group are faced with several difficulties. With powerful transition-metal oxidants, the initial oxidation products are almost always more susceptible to oxidation than the starting material. When a hydrocarbon is oxidized, it is likely to be oxidized to a carboxylic acid, with chain cleavage by successive oxidation of alcohol and carbonyl intermediates. There are a few circumstances under which oxidations of hydrocarbons can be synthetically useful processes. One group involves catalytic industrial processes. Much effort has been expended on the development of selective catalytic oxidation processes and several have economic importance. We focus on several reactions that are used on a laboratory scale. 

The hydrolysis of an ester to alcohol and acid (1) and the esterification of a carboxylic acid with an alcohol (2) are shown here as an example of the Sn2 mechanism. Both reactions are made easier by the marked polarity of the C=0 double bond. In the form of ester hydrolysis shown here, a proton is removed from a water molecule by the catalytic effect of the base B. The resulting strongly nucleophilic OH ion attacks the positively charged carbonyl C of the ester (la), and an unstable sp -hybridized transition state is produced. From this, either water is eliminated (2b) and the ester re-forms, or the alcohol ROH is eliminated (1b) and the free acid results. In esterification (2), the same steps take place in reverse. 

Figure 7.6 Schematic representation of the interaction of water molecules with carboxylic acid (a), alcohol (b), -NH and carbonyl groups (c) and amide groups (d).

After reaction with SF4, all OH groups are converted to F groups [9]. The reactions of carboxylic acids with SF4 give acyl fluorides, and alcohols and hydroperoxides give alkyl fluorides. SF4 treatment carried out on a pre-photooxidized film leads to a decrease in absorption in the carbonyl vibration region (1698, 1710, 1732 and 1753 cm-1) and to the formation of two new bands at 1813 and 1841 cm-1 (Figure 30.2). 

Sodium hypochlorite is used for the epoxidation of double bonds [659, 691] for the oxidation of primary alcohols to aldehydes [692], of secondary alcohols to ketones [693], and of primary amines to carbonyl compounds [692] for the conversion of benzylic halides into acids or ketones [690] for the oxidation of aromatic rings to quinones [694] and of sulfides to sulfones [695] and, especially, for the degradation of methyl ketones to carboxylic acids with one less carbon atom [655, 696, 697, 695, 699] and of a-amino acids to aldehydes with one less carbon [700]. Sodium hypochlorite is also used for the reoxidation of low-valence ruthenium compounds to ruthenium tetroxide in oxidations by ruthenium trichloride [701]. 

Phylogeny of Hydrocarbon Chains. An important chapter in the geochemistry of oil shales is the one dealing with the "genealogy" of the final products - the hydrocarbons. The results (28) of the phylogenetic study of the serie carboxylic acids aldehydes alcohols - hydrocarbons from the bitumen of a sample from the Irati F. showed no correlation between n-acids (C ) (C-.-.-C ) and n-tty drocarbons (C (the linear correlation coefficient 6 = 0,15). Between n-carboxylic acids (C ) and normal carbonyl/hydroxy com... 

Don t confuse a carboxylic acid with a ketone or an alcohol. Carboxylic acids have entirely different properties and reactivities than either ketones or alcohols. In particular, the proton (H+) on the oxygen in a carboxylic acid is unusually acidic (hence the name ), for reasons we talk about later in this chapter in the section Reactivity of the Carbonyl Group. ... 

Reduction of carboxylic acids with 1 mole of LiAlH4 consumes three of the four hydrides that are available,25 and the reduction product is an alcohol. The acid has the acidic hydrogen of the OH unit, and this reacts first. Subsequent reduction of the carbonyl unit leads to the usual alkoxyaluminate, which is hydrolyzed to the alcohol. Reduction of acid 20 to alcohol 21 in 87% yield is a useful example.26 Reduction of acids to alcohols bearing a heteroatom at the a-position is also possible. 

Generation of the carboxylic acid and aldehyde at the C-13 position of the salvinorin A scaffold has granted access to a variety of chemical methods for the development of salvinorin A analogs with a C-13 carbonyl moiety. From carboxylic acid 125, alcohols and ethers at C-13 have been synthesized [44]. The primary alcohol at C-13 (127) was produced in 46% yield by reducing carboxylic acid 125 using BHs THF (Scheme 21). Alcohol 127 was then alkylated using alkyl iodides in the presence of Ag20 to afford alkyl ethers (128 and 129) in 12-15% yield. The primary alcohol was also acetylated (130) in 11% yield with acetic anhydride and EtsN. 

Alcohols with at least one hydrogen attached to the hydroxyl-bearing carbon can be oxidized to carbonyl compounds. Primary alcohols give aldehydes, which may be further oxidized to carboxylic acids. Secondary alcohols give ketones. Notice that as an... 

N-Substituted caprolactams were imexpectedly formed by the reaction of an alcohol or carboxylic acid with carbonyl diimidazole and 1.8-diazabicy-cloundecane (DBU). In these reaaions, DBU acts as a nucleophile on an N-acylimidazole intermediate to produce the acylated DBU intermediate 2 which undergoes hydrolytic ring opening to give excellent yields of the N-substituted caprolactam derivatives 3 (13TL5181). 

Conversion to Acid Haiides (Section 17.8) Acid chlorides, the most common and widely used of the acid halides, are prepared by treating a carboxylic acid with thionyl chloride. The mechanism, similar to that of the conversion of alcohols to chloroalkanes, involves initial chlorosulfite formation, followed by nucleophilic attack of chloride ion on the carbonyl carbon to give a tetrahedral carbonyl addition intermediate, which decomposes to give the acid chloride, SOj, and chloride ion. 

As seen in Scheme 8.55, alcohols react,reversibly, with carboxylic acids to produce esters and water. As will be discussed later (Chapter 10), but should be clear from the scheme, the hydrolysis (reaction with water) of esters produces carboxylic acids and alcohols. In a similar vein, if an ester (such as methyl ethanoate [methyl acetate, CH3CO2CH3],Table 8.6, item 17) is treated with an excess of alcohol (such as cyclo-hexanol,Table 8.6, item 17) in the presence of an acid catalyst and (generally) heated at a temperature above the distillation temperature of the alcohol with which the acid is esterilied, ester interchange can be effected (Scheme 8.58) through the addition of the higher boiling alcohol to the carbon of the carbonyl followed by expulsion of the lower boiling one. 

Reaction time has to be as short as possible in order to suppress side reactions. Especially the conversion of alcohols to carboxylic acids with one more C-atom, which will be discussed subsequently, or formation of ethers and free acids may be undesirable reactions [504]. The carbonylation rate of olefins with carbon monoxide/ROH in the presence of Co carbonyls can be accelerated remarkably by addition of small portions of hydrogen to carbon monoxide, which favors the formation of hydrocarbonyl. The same effect can be achieved by addition of pyridine. 

Anderson, R., Griffin, K., Johnston, P.,etal. (2003). SelectiveOxidationof Alcohols to Carbonyl Compounds and Carboxylic Acids with Platinum Group Metal Catalysts, Adv. Synth. Catal., 345, pp. 517-523. 

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