Acetal formation., by azeotropic distillation

The formation of ethyl isopropylidene cyanoacetate is an example of the Knoevenagel reaction (see Discussion before Section IV,123). With higher ketones a mixture of ammonium acetate and acetic acid is an effective catalyst the water formed is removed by azeotropic distillation with benzene. The essential step in the reaction with aqueous potassium cyanide is the addition of the cyanide ion to the p-end of the ap-double bond ... 

Acetal formation is reversible (K for MeCHO/EtOH is 0-0125) but the position of equilibrium will be influenced by the relative proportions of R OH and H2O present. Preparative acetal formation is thus normally carried out in excess R OH with an anhydrous acid catalyst. The equilibrium may be shifted over to the right either by azeotropic distillation to remove H2O as it is formed, or by using excess acid catalyst (e.g. passing HCl gas continuously) to convert H2O into the non-nucleophilic H3O . Hydrolysis of an acetal back to the parent carbonyl compound may be effected readily with dilute acid. Acetals are, however, resistant to hydrolysis induced by bases—there is no proton that can be removed from an oxygen atom, cf. the base-induced hydrolysis of hydrates this results in acetals being very useful protecting groups for the C=0 function, which is itself very susceptible to the attack of bases (cf. p. 224). Such protection thus allows base-catalysed elimination of HBr from the acetal (27), followed by ready hydrolysis of the resultant unsatu-... 

Acetalization with Diols. 1,3-Dioxolane (five-member ring acetal) is the most widely used C=0 protecting group. The formation of acetals with diols provides an entro-pic advantage over the use of two equivalents of an alcohol. The water formed is removed by azeotropic distillation. 

The liquid effluent from the flash drum is first degassed. The vapors consisting of methyl iodide and formate, acetaldehyde and methyl acetate, are dissolved in the azeotrope produced by the subsequent acetic add dehydration column. The degassed arid mixture is then distilled to remove the light components and the cobalt iodide, which is recycled to the reactor in the form of an aqueous slurry. This mixture is then dehydrated and purified by azeotropic distillation. The third compound employed is one of the reaction products (methyl acetate, bp10l3 = 70.4°C, water content 8.5 per cent weight). The column has about 60 trays.. ... 

In reductive alkylation of aromatic amines the water formed is often removed by azeotropic distillation before the hydrogenation or a preformed Schiff base may be reduced (cf. page 554). These procedures are particularly suitable for reductive alkylation of ketones886,1006 in order to counter reduction of the ketone to the secondary alcohol. Here too formation of the alcohol can be repressed by adding a catalytic amount of ammonium chloride or acetic acid to the ketone-amine mixture (cf. page 521). 

Thiazolidones are another class of heterocycles that attract much attention because of their wide ranging biological activity [106], They are usually synthesized by three-component condensation of a primary amine, an aldehyde, and mercapto-acetic acid with removal, by azeotropic distillation, of the water formed [107]. The reaction is believed to proceed via imine formation then attack of sulfur on the imine carbon. Finally, an intramolecular cyclization with concomitant elimination of water occurs, generating the desired product. The general applicability of the reaction is limited, however, because it requires prolonged heating with continuous removal of water. To circumvent these difficulties and to speed up the synthesis, Miller et al. developed a microwave-accelerated three-component reaction for the synthesis of 4-thiazolidinones 63 [108]. In this one-pot procedure, a primary amine, an aldehyde, and mercaptoacetic acid were condensed in ethanol under MW conditions for 30 min at 120 °C (Scheme 17.44). The desired 4-thiazolidinones 63 were obtained in 55-91% yield. 

Methyl, ethyl, benzyl, benzhydryl, p-nitrobenzyl, p-methoxy-benzyl, 4-picolyl, j3j -trichloroethyl, j3-methylthioethyl, /J-p-toluenesulphonylethyl, and -p-nitrophenylthioethyl esters may be prepared directly from the acid and alcohol. TTie most usual method [4, 5] consists of heating the acid and an excess of the alcohol with an acid catalyst (e.g., Fischer-Speier, hydrochloric or sulphuric acid). The extent of reaction is improved if the water formed is removed by azeotropic distillation with an inert solvent (benzene, carbon tetrachloride, or chloroform). Considerable variation is possible in the natvire of the acid catalyst thus phosphoric acid [6], aryl sulphonic acids [7, 8, 9], alkyl sulphates [10], and acidic ion-exchange resins [11] may be employed. Removal of the water by azeotropic distillation during the formation of methyl esters is difficult and Brown and Lovette [12] introduced the novel reagent acetone dimethyl acetal (7) for the direct formation of methyl esters. In the presence of a trace of methanol and an acid catalyst the reagent acts as a scavenger of water formed by esterification and liberates further methanol for reaction. 

Procedure for 1,3-dioxolane formation with ethyl acetoacetate by azeotropic removal of water.128a Ethyl acetoacetate (30 g, 0.23 mol), ethane-1,2-diol (16g, 0.248 mol), a crystal of toluene-p-sulphonic acid and benzene (50 ml) (CAUTION) were placed in a round-bottomed flask fitted with a Dean and Stark water separator (Fig. 2.31(a)) and a reflux condenser. The reaction mixture was heated until no more water collected. The product was fractionally distilled under reduced pressure to give the cyclic acetal (35 g, 87%), b.p. 99.5-101 °C/17-18 mmHg. 

Acetone steady-state concentrations are maintained at a low level through subsequent side reactions involving formation of heavy ends by condensation of acetone and through its removal from streams of light ends using countercurrent dis-tillation/extraction methods [64a-cj. The formation of azeotropes of acetone, methyl acetate and methyl iodide preclude the separation of acetone by conventional distillation techniques. 

There are many examples of the application of CD or RD for esterification.f" Esterification of methanol or ethanol with acetic acid forms methyl acetate or ethyl acetate, respectively. Methyl acetate is important in the manufacture of polyesters and is an important solvent for cellulose while ethyl acetate is used in inks, fragrances, and pharmaceuticals. The manufacture of high-purity methyl acetate is difficult because of the equilibrium limitation and also the formation of azeotropes. The production of methyl acetate by Eastman Chemical Co. was the first commercial application of RD using a homogeneous liquid acid catalyst. Only one RD column and two smaller columns for processing sidestreams are required while in the conventional methyl acetate synthesis, two reactors and eight distillation columns are required. 

The formation of minimum-boiling mixtures makes azeotropic distillation a useful tool in those cases where separation by fractional distillation is not feasible. In the example cited for separation operation (10) in Table 1.1, n-butyl acetate, which forms a heterogeneous minimum-boiling azeotrope with water, is used to facilitate the separation of acetic acid from water. The azeotrope is taken overhead, the acetate and water layers are decanted, and the MSA is recirculated. 

The ZnO precursor was synthesized by direct precipitation from zinc acetate and ammonium carbonate [6,7]. ZnO nanopartides were synthesized by caldnation of the precursor at 450 °C for 3h and calcination after the heterogeneous azeotropic distillation of the precursor. The synthesized ZnO nanopartides were characterized by FT-IR, XRD, and TEM. It is conduded that the heterogeneous azeotropic distillation of the precursor effectively reduced the formation of hard agglomerates. The photocatalytic activity of the synthesized ZnO nanopartides is high. 

Carboxylic acids may be converted to esters directly by using a primary or secondary alcohol and a small amount of strong acid catalyst. This is a reversible equilibrium, where ester formation is favored by using excess of the alcohol or by removing the water produced. Azeotropic distillation of the water or consumption of the water by concurrent hydrolysis of an acetal is usually effective. 

Esters of medium volatility are capable of removing the water formed by distillation. Examples are propyl, butyl, and amyl formates, ethyl, propyl, butyl, and amyl acetates, and the methyl and ethyl esters of propionic, butyric, and valeric acids. In some cases, ternary azeotropic mixtures of alcohol, ester, and water are formed. This group is capable of further subdivision with ethyl acetate, all of the ester is removed as a vapor mixture with alcohol and part of the water, while the balance of the water accumulates in the system. With butyl acetate, on the other hand, all of the water formed is removed overhead with part of the ester and alcohol, and the balance of the ester accumulates as a high boiler in the system. 

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