Catalysis with alcohols

Many of the most interesting and useful reactions of aldehydes and ketones involve trans formation of the initial product of nucleophilic addition to some other substance under the reaction conditions An example is the reaction of aldehydes with alcohols under con ditions of acid catalysis The expected product of nucleophilic addition of the alcohol to the carbonyl group is called a hemiacetal The product actually isolated however cor responds to reaction of one mole of the aldehyde with two moles of alcohol to give gem mal diethers known as acetals... 

Acetals are readily formed with alcohols and cycHc acetals with 1,2 and 1,3-diols (19). Furfural reacts with poly(vinyl alcohol) under acid catalysis to effect acetalization of the hydroxyl groups (20,21). Reaction with acetic anhydride under appropriate conditions gives the acylal, furfuryUdene diacetate... 

In the esterification of organic acids with alcohols, it has been shown that in most cases under acid catalysis, the union is between acyl and alkoxy groups. Acid hydrolysis of acetoxysuccinic acid gives malic acid with retention of configuration at the asymmetric carbon atom (11) ... 

Phenyl isocyanates are generally more reactive than alkyl isocyanates in their reactions with alcohols, but with CuCl catalysis even alkyl isocyanates will react readily with primary, secondary, or tertiary alcohols (45-95% yield). ... 

AcCl, NaOH, dioxane, Bu4N HSO, 25°, 30 min, 90% yield. Phase-transfer catalysis with tetra-n-butylammionium hydrogen sulfate effects acylation of sterically hindered phenols and selective acylation of a phenol in the presence of an aliphatic secondary alcohol. 

Goi. As noted previously, an a-chlorine atom renders a ring-nitrogen atom very weakly basic. Cyanuric chloride (5) is a very weak base both because s-triazines are of low basicity and because each of the ring-nitrogen atoms is alpha to two chlorine atoms. Hence, this compound should be insensitive to acid catalysis or acid autocatalysis and this has been observed for the displacement of the first chlorine atom with alcohols in alcohol-acetone solution and with water (see, however. Section II,D,2,6). 

Diazomethane is a yellow gas that is toxic and explosive but that may be handled safely in solution in ether. It reacts immediately with an acid to liberate nitrogen and form the methyl ester. Its reaction with alcohols to form methyl esters requires catalysis by a Lewis acid. The procedures illustrate the use of this reagent as a methylating agent (see Chapter 17, Section III, for preparation of diazomethane). 

I. S. Bechara, The Mechanism of Tin-Amine Synergism in the Catalysis of Isocyanate Reaction with Alcohols, in Urethane Chemistry and Applications, ACS Symposium Series 172, K. N. Edwards, (Ed.), American Chemical Society, Washington, DC, 1981. 

Kunz and Sager also demonstrated the effectiveness of this procedure. Under BFj catalysis, reactions (in CH2CI2) of 18,20a, and 45a with alcohols [including benzyl alcohol, cholesterol, their silyl ethers, and A-(benzyloxy-... 

This chapter compares the reaction of gas-phase methylation of phenol with methanol in basic and in acid catalysis, with the aim of investigating how the transformations occurring on methanol affect the catalytic performance and the reaction mechanism. It is proposed that with the basic catalyst, Mg/Fe/0, the tme alkylating agent is formaldehyde, obtained by dehydrogenation of methanol. Formaldehyde reacts with phenol to yield salicyl alcohol, which rapidly dehydrogenates to salicyladehyde. The latter was isolated in tests made by feeding directly a formalin/phenol aqueous solution. Salicylaldehyde then transforms to o-cresol, the main product of the basic-catalyzed methylation of phenol, likely by means of an intramolecular H-transfer with formaldehyde. With an acid catalyst, H-mordenite, the main products were anisole and cresols moreover, methanol was transformed to alkylaromatics. 

Acyl chlorides are highly reactive acylating agents and react very rapidly with alcohols and other nucleophiles. Preparative procedures often call for use of pyridine as a catalyst. Pyridine catalysis involves initial formation of an acyl pyridinium ion, which then reacts with the alcohol. Pyridine is a better nucleophile than the neutral alcohol, but the acyl pyridinium ion reacts more rapidly with the alcohol than the acyl chloride.103... 

The combination of carboxyl activation by DCCI and catalysis by DMAP provides a useful method for in situ activation of carboxylic acids for reaction with alcohols. The reaction proceeds at room temperature.119... 

By the way, TV-trifluoroacetylimidazole and AT-trichloroacetylimidazole are both such remarkably strong acylation agents that base catalysis is not necessary in their reactions with alcohols to the corresponding esters.[18],[19]... 

Imidazolides of aromatic sulfonic acids react much more slowly in alcoholysis reactions than the carboxylic acid imidazolides. Although the reaction with phenols is quantitative when a melt is heated to 100 °C for several hours, with alcohols under these conditions only very slight alcoholysis is observed. In the presence of 0.05 equivalents (catalytic amount) of sodium ethoxide, imidazole sodium, of NaNH2, however, imidazolides of sulfonic acids react with alcohols almost quantitatively and exothermically at room temperature in a very short time to form sulfonic acid esters (sulfonates). (If the ratio of sulfonic acid imidazolide to alcoholate is 1 2, ethers are formed see Chapter 17). The mechanism of catalysis by base corresponds to that operative in the synthesis of carboxylic esters by the imidazolide method. Because of the more pronounced nucleophilic character of alkoxide ions, sulfonates can also be prepared in good yield by alcoholysis of their imidazolides in the presence of hydroxide ions i.e., with alcoholic sodium hydroxide. 45 Examples of syntheses of sulfonates are presented below. 

Esters are fairly unreactive. Hydrolysis of esters to form alcohols is primarily accomplished through catalysis with strong bases, like NaOH. This is called saponification. The reaction can also be acid-catalyzed, but this method has two drawbacks. 

Aside from alcohols, other oxygen nucleophiles have also participated in hydroalkoxylation reactions with alkynes. The most common of these are 1,3-dicarbonyl compounds, whose enol oxygens are readily available to add to alkynes. Cyclization reactions of this type have been carried out under Pd(0) catalysis with various aryl or vinyl iodides or triflates, often in the presence of CO, affording the corresponding furan derivatives (Equation (95)).337-340 A similar approach employing cyclic 1,3-diketones has also been reported to prepare THFs and dihydropyrans under Pd, Pt, or W catalysis.341 Simple l-alkyn-5-ones have also been isomerized to furans under the influence of Hg(OTf)2.342... 

Primary alcohols are selectively silylated by 1 and N(C,H5)j in CH,CU at 25°. Silylation of secondary alcohols is effected by catalysis with DMAP, and even tertiary alcohols can be silylated by 1 in DMF catalyzed by DMAP. 

In this chapter we will discuss some aspects of the carbonylation catalysis with the use of palladium catalysts. We will focus on the formation of polyketones consisting of alternating molecules of alkenes and carbon monoxide on the one hand, and esters that may form under the same conditions with the use of similar catalysts from alkenes, CO, and alcohols, on the other hand. As the potential production of polyketone and methyl propanoate obtained from ethene/CO have received a lot of industrial attention we will concentrate on these two products (for a recent monograph on this chemistry see reference [1]). The elementary reactions involved are the same formation of an initiating species, insertion reactions of CO and ethene, and a termination reaction. Multiple alternating (1 1) insertions will lead to polymers or oligomers whereas a stoichiometry of 1 1 1 for CO, ethene, and alcohol leads to an ester. 

Fig. 9.2. Simplified reaction mechanisms in the hydrolytic decomposition of organic nitrites. Pathway a Base-catalyzed hydrolysis with liberation of nitrite. Pathway b Reversible nitro-syl exchange between organic nitrites and alcohols. Pathway c General acid catalysis with concerted mechanism in the acid hydrolysis of organic nitrites.

Enantiomerically pure phenyldiazoacetic esters [1217] and vinyldiazoacetic esters [956] react with alcohols upon transition metal catalysis to yield a-alkoxyesters with low diastereoselectivity (< 53% de). 

Compound 264 is unexpectedly stable against light, but can easily be oxidized to the sulfoxide 265 and the sulfone 266. Sulfoxide 265 can be isolated and a-activated by reaction with acetic anhydride (Scheme 4.46). a-Acetoxylated tetrahydrothio-phene 267 has 0,S-acetal-like reactivity and can be functionalized with various alcohols or thiols under acid catalysis with camphorsulfonic acid (CSA) (268). 

The acetoxy group of 9-(l-acetoxyethyl)carbazole is easily displaced with alcohols. Easy displacement of a similarly situated halogen can be achieved, as has been noted before (see Section II,C,2) thus methanol converts 9-(l-chloro-2-iodoethyl)carbazole to 9-(2-iodo-l-methoxyethyI) car-bazole. Elimination of acetic acid or ethanol by strongly heating 9-(l-acetoxyalkyl)- or 9-(l-ethoxyalkyl)carbazoles gives 9-vinylcarbazoles. In the absence of acid, ( )-alkenes are produced, but acid catalysis leads to a mixture of E and Z isomers. Acetyl chloride in pyridine also effects ethanol elimination. ... 

Phenols and alcohols also react with substituted thiocarbonyl ylides, although for the reaction with alcohols, acid catalysis is usually recommended (36,38,41,99). Some NH-azoles are sufficiently acidic to give 1,3-adducts without the addition of a... 

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