Carbonyl compounds acetalization/ketalization

Carbonyl Compounds. Cychc ketals and acetals (dioxolanes) are produced from reaction of propylene oxide with ketones and aldehydes, respectively. Suitable catalysts iaclude stannic chloride, quaternary ammonium salts, glycol sulphites, and molybdenum acetyl acetonate or naphthenate (89—91). Lactones come from Ph4Sbl-cataly2ed reaction with ketenes (92). 

Grignard reagents, it must be remembered, are severely restricted in the functional groups that can be present in either the organometallic or carbonyl compound. Alkene, ketal, and acetal groups ordinarily cause no difficulty, but unprotected OH, NH, or SH groups and carbonyl groups cannot be present. 

The most commonly used protected derivatives of aldehydes and ketones are 1,3-dioxolanes and 1,3-oxathiolanes. They are obtained from the carbonyl compounds and 1,2-ethanediol or 2-mercaptoethanol, respectively, in aprotic solvents and in the presence of catalysts, e.g. BF, (L.F. Fieser, 1954 G.E. Wilson, Jr., 1968), and water scavengers, e.g. orthoesters (P. Doyle. 1965). Acid-catalyzed exchange dioxolanation with dioxolanes of low boiling ketones, e.g. acetone, which are distilled during the reaction, can also be applied (H. J. Dauben, Jr., 1954). Selective monoketalization of diketones is often used with good success (C. Mercier, 1973). Even from diketones with two keto groups of very similar reactivity monoketals may be obtained by repeated acid-catalyzed equilibration (W.S. Johnson, 1962 A.G. Hortmann, 1969). Most aldehydes are easily converted into acetals. The ketalization of ketones is more difficult for sterical reasons and often requires long reaction times at elevated temperatures. a, -Unsaturated ketones react more slowly than saturated ketones. 2-Mercaptoethanol is more reactive than 1,2-ethanediol (J. Romo, 1951 C. Djerassi, 1952 G.E. Wilson, Jr., 1968). 

A carbonyl group can be protected as a sulfur derivative—for example, a dithio acetal or ketal, 1,3-dithiane, or 1,3-dithiolane—by reaction of the carbonyl compound in the presence of an acid catalyst with a thiol or dithiol. The derivatives are in general cleaved by reaction with Hg(II) salts or oxidation acidic hydrolysis is unsatisfactory. The acyclic derivatives are formed and hydrolyzed much more readily than their cyclic counterparts. Representative examples of formation and cleavage are shown below. 

Acyclic monothio acetals and ketals can be prepared directly from a carbonyl compound or by transketalization, a reaction that does not involve a free carbonyl group, from a 1,3-dithiane or 1,3-dithiolane. They are cleaved by acidic hydrolysis or Hg(II) salts. 

The second step in acetal and ketal hydrolysis is conversion of the hemiacetal or hemiketal to the carbonyl compound. The mechanism of this step is similar to that of the first step. Usually, the second step is faster than the initial one. Hammett a p plots and solvent isotope effects both indicate that the transition state has less cationic character than... 

Arrange the carbonyl compounds in each group in order of decreasing rate of hydrolysis of their respective diethyl acetals or ketals. Explain your reasoning. 

Reductive alkylations have been carried out successfully with compounds that are not carbonyls or amines, but which are transformed during the hydrogenation to suitable functions. Azides, azo, hydrazo, nitro and nitroso compounds, oximes, pyridines, and hydroxylamines serve as amines phenols, acetals, ketals, or hydrazones serve as carbonyls 6,7,8,9,12,17,24,41,42,58). Alkylations using masked functions have been successful at times when use of unmasked functions have failed (2). In a synthesis leading to methoxatin, a key... 

Conversion to acetals or ketals is a very general method for protecting aldehydes and ketones against nucleophilic addition or reduction. Ethylene glycol, which gives a dioxolane derivative, is frequently employed for this purpose. The dioxolane derivative is usually prepared by heating the carbonyl compound with ethylene glycol in the presence of an acid catalyst, with provision for azeotropic removal of water. 

Acetals and ketals can be prepared under very mild conditions by reaction of the carbonyl compound with an alkoxytrimethylsilane, using trimethylsilyl trifluoromethylsulfonate as the catalyst.92... 

Balme G, Gore J (1983) Conversion of acetals and ketals to carbonyl compounds promoted by titanium tetrachloride. J Org Chem 48 3336-3338... 

Carbonyl compounds react with glycols in anhydrous acid to form 1,3-cyclic ethers. These are called acetals if formed from aldehydes, and ketals if formed from ketones. 

Addition of alcohol to carbonyl compounds preparation of acetal and ketal... 

In a similar fashion to the formation of hydrate with water, aldehyde and ketone react with alcohol to form acetal and ketal, respectively. In the formation of an acetal, two molecules of alcohol add to the aldehyde, and one mole of water is eliminated. An alcohol, like water, is a poor nucleophile. Therefore, the acetal formation only occurs in the presence of anhydrous acid catalyst. Acetal or ketal formation is a reversible reaction, and the formation follows the same mechanism. The equilibrium lies towards the formation of acetal when an excess of alcohol is used. In hot aqueous acidic solution, acetals or ketals are hydrolysed back to the carbonyl compounds and alcohols. 

P-Bromo acetals and ketals. These useful derivatives are generally prepared by addition of an a./J-unsaturated carbonyl compound to a solution of HBr in the diol. The same products can be obtained by addition of HBr to the a,/J-enal or enone followed by acetalization. The method is improved if only a stoichiometric amount of HBr is used. Dicinnamalacetone (equation I)2 is used to determine the end point. Hydrogen bromide is added to the initially yellow solution until a red color persists. 

Camphor- 10-sulfonic acid, 62 Unsaturated acetals or ketals Nickel boride, 197 (2R,4R)-Pentanediol, 237 Acetylenic carbonyl compounds a,p-Unsaturated acetylenic carbonyl compounds... 

The conversion of an a, -unsaturated aldehyde or ketone into an allylic acetal or ketal, followed by SN2 -type attack of a nucleophile, leads, after hydrolysis of an initially formed enol ether, to a fi-sub-stituted carbonyl compound. The overall sequence (Scheme 23) is equivalent to a direct conjugate addition, but has the advantage that it allows the temporary introduction of a chiral auxiliary group if a chiral (C2-symmetric) diol is used in the acetalization step, die subsequent nucleophilic addition leads to a mix-... 

The hydration of carbonyl compounds, along with hemiketal and ketal or hemicacetal and acetal formation, were studied in K. B. Wiberg, K. M. Morgan and H. Maltz, J. Am. Chem. Soc., 116, 11067 (1994). 

Cleavage of ethers. The actual reagent formed from these two reagents is believed to be iodotrichlorosilane and is similar to iodotrimethylsilane for cleavage of ethers but somewhat more regioselective. It also cleaves acetals and ketals quantitatively to the carbonyl compound at room temperature. 

A new, direct route to 0,S-acetals is based in part on the ability of trimethylsilyl triflate to mediate synthesis of 0,0-acetals from carbonyl compounds and silyl ethers (10, 439). Thus reaction of 1 1 mixtures of a silyl ether and phenylthiotrimethylsilane with an aldehyde in the presence of catalytic to stoichiometric amounts of trimethylsilyl triflate can give 0,S-acetals in 37-93% yield. Acetone is amenable to this 0,S-ketalization, but reactions with cyclohexanone result mainly in 0,0-ketals. 

When an aldehyde or ketone is treated with an excess of alcohol in the presence of an acid catalyst, two molecules of alcohol are added to the carbonyl compound to give an acetal or a ketal, respectively (Following fig.)- The final product is tetrahedral. 

All the stages in this mechanism are reversible and so it is possible to convert the acetal or ketal back to the original carbonyl compound using water and an aqueous acid as catalyst. Since water is added to the molecule in the reverse mechanism, this is a process known as hydrolysis. 

This is also the case for 2-substituted furans, however, mixtures of acetal- and ketal-type oxetanes (e.g., for 87b) were obtained [82]. The use of furans with steric demanding substituents (e.g., 87c) [66a,83], or a acetyl substituent (e.g., 87d) [66b] at the 2-position largely improves the regio-selectivity. A huge number of carbonyl compounds have been investigated in the last 10 years by Zamojski [84] and especially by Schreiber [85] who used furan-carbonyl adducts as intermediates in total synthesis of natural... 

The acetals and ketals which will be considered are those formed from the tetritols, pentitols, and hexitols, on the one hand, and the simpler carbonyl compounds (e.g. acetone and benzaldehyde), on the other. 

In this section, consideration will be given to the actual processes of acetal- or ketal-formation and not to the more indirect methods by which acetals and ketals of the polyhydric alcohols may be synthesized from compounds (e.g. derivatives of the monosaccharides) containing preformed alkylidene or arylidene groupings. The condensation of a carbonyl compound with a glycol is facilitated by acidic catalysts, and, since the reaction is reversible, by dehydration. The catalysts most frequently employed are concentrated sulfuric, hydrochloric and hydro-bromic acids, gaseous hydrogen chloride, zinc chloride and cupric sulfate others are phosphorus pentoxide, sulfosalicylic acid, and anhydrous sodium sulfate. The formation of benzylidene compounds is promoted less efficiently by phosphorus pentoxide than by either concentrated sulfuric acid or concentrated hydrochloric acid 1" the reaction is assisted by chloro- and nitro-substituents on the aromatic nucleus, but hindered by methyl- and methoxy-groups.18... 

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