Acetalization of aldehydes and ketones

This very mild Noyori acetalization has found wide application for the preparation of dialkyl or ethylene acetals of aldehydes and ketones, affording, e.g. with... 

Dimethyl acetals of aldehydes and ketones, for example benzaldehyde dimethyl acetal 121, and hemiacetals, react with allyltrimethylsilane 82 at -78 °C in CH2CI2, in the presence of TMSOTf 20 [169], trimethyhodosilane TIS 17 [159, 170],... 

Amides reacted with acetals of aldehydes and ketones to form JV-(a-alkoxyalk-yl)amides, which upon pyrolysis over alumina at 290-300 °C yielded enamides643. It was found that it was possible to obtain the enamide directly from the acetal by refluxing it in the presence of an acid (equation 48). 

The acetalization of aldehydes and ketones with alcohols is catalyzed by SbCb in the presence of Fe or Al (Scheme 14.5) [21]. The selective acetahzation of aldehydes can also be performed by combined use of Sb(OR)3 (R=Et, iPr) and allyl bromide [26]. Sb(OEt)3 promotes intermolecular amidation between amines and esters or carboxylic acids [27]. When tetraamino esters are used as substrates, the antimony(Ill)-templated macrolactamization occurs to yield macrocychc spermine alkaloids (Scheme 14.6). 

Oxarsinanes (53), which may be considered as 0,As-acetals of aldehydes and ketones, are easily accessible by the acid-catalyzed reaction of 3-hydroxypropylarsines with aldehydes and ketones <77TH 626-01 >. The 1,3-thiarsinanes (54) are obtained in a similar way starting from 3-mercaptopropylarsines (Equation (9)) <76TH 626-m, 77TH 626-01 >. 

Addition of halogens to enol acetates of aldehydes and ketones for preparation of <%-halogeno aldehydes and ketones is described on page 187. 

Bicyclic 1,3-dioxepanes (8) and (10) were prepared in a stereoselective manner by direct acetalization of aldehydes and ketones with diols (7) and (9 X = H), or chlorendic diol (9 X = Cl) (Scheme 2) <75BSF1763,76USP3984438>. For another approach to dioxepane (10) by [4 4-2] cycloaddition of 2-ethyl- or 2-isobutyryl-4,7-dihydro-1,3-dioxepin with cyclopentadiene dimers see Section 9.11.1.2.2. Acetalization of hexafluoroacetone with 1,4-butanediol to 1,3-dioxepane (11) has been effected with dicyclohexyl carbodiimide as condensating agent <87MI 9ll-0l>. 

Acetalization. Distannoxanes of this type are useful catalysts for esterification (15,89) because they can activate both alcohols and carbonyl groups on the same template. Of a number of stannoxanes, 1 is found to be the most efficient catalyst for acetalization of aldehydes and ketones with ethylene glycol. In particular it can promote acetalization of cyclic a,)3-enones, which u,sually proceeds in low yield. 

The acetalization of aldehydes and ketones were found by Graham et al. to be catalyzed by In(OTf)3 (1 mol%) to give excellent yields of acetals or cyclic acetals within 10 minutes at room temperature using trialkyl orthoformates or diols respectively [261]. Varma et al. had also found success with their synthesized... 

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). 

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... 

A review discusses the condensation of aldehydes and ketones with glycerol to give 1,3-dioxanes and 1,3-dioxolanes. The chemistry of 0 0 and 0 S acetals has been reviewed, and a recent monograph discusses this area of protective groups in a didactic sense. ... 

A particularly common cr-substitution reaction in the laboratory is the halogenation of aldehydes and ketones at their a- positions by reaction with Cl2, Br2, or I2 in acidic solution. Bromine in acetic acid solvent is often used. 

Reaction of aldehydes and ketones with methanol or glycols at ambient temperature in the presence of excess trimethylchlorosilane (TCS) 14 to form acetals, hexamethyldisiloxane 7, and HCl is achieved very simply [28]. Thus cyclohexanone and diacetyl react with free glycol and TCS 14 to give the acetals 392 and 405 in 95% yield [28]. Reaction of phenylglyoxal with methanol in the presence of trimethylchlorosilane 14 affords the acetal 406 in 83% yield [28], whereas catechol 79 is converted by pivaldehyde into acetal 407 in 91% yield [29] (Scheme 5.5). 

Alternatively, iminium salts such as 549 or 551 can also be synthesized by reaction of aldehydes and ketones with 0,N- or N,N-acetals in the presence of TMSOTf 20 [121], MejSiCl 14 [122], Me2SiCl2 48, or MeSiClj [123]. The reactions... 

Protective Groups for Diols. Diols represent a special case in terms of applicable protecting groups. 1,2- and 1,3-diols easily form cyclic acetals with aldehydes and ketones, unless cyclization is precluded by molecular geometry. The isopropylidene derivatives (also called acetonides) formed by reaction with acetone are a common example. 

A mixture of 1,4-dioxane and water is often used as the solvent for the conversion of aldehydes and ketones by H2Se03 to a-dicarbonyl compounds in one step (Eq. 8.117).331 Dehydrogenation of carbonyl compounds with selenium dioxide generates the a, (i-unsaturated carbonyl compounds in aqueous acetic acid.332 Using water as the reaction medium, ketones can be transformed into a-iodo ketones upon treatment with sodium iodide, hydrogen peroxide, and an acid.333 Interestingly, a-iodo ketones can be also obtained from secondary alcohol through a metal-free tandem oxidation-iodination approach. 

Several other miscellaneous heterogeneously catalyzed reactions have been performed in the liquid phase. Hexane was successfully oxyfunctionalized with aqueous hydrogen peroxide by use of the zeolite TS-1 catalyst [50] and microwave-promoted acetalization of a number of aldehydes and ketones with ethylene glycol proceeded readily (2 min) in the presence both of heterogeneous (acidic alumina) and homogeneous (PTSA, Lewis acids) catalysts [51], Scheme 10.7. 

Addition of ketene silyl acetals to aldehydes and ketones is also mediated by achiral palladium(ll) acetate-diphosphine complexes (Equation (109)).46S,46Sa Although the precise mechanism is still unclear, high catalytic activity may be ascribed to the intermediacy of palladium enolates. 

The hydroxyl groups of aldonolactones react with a variety of aldehydes and ketones to give the corresponding acetal derivatives. Treatment of the salts of aldonic acids with benzaldehyde and hydrochloric acid or zinc chloride as catalysts give benzylidene derivatives of aldonic acids or aldonolactones (3). 

Scheme 16 Transformation of aldehydes and ketones to a-hydroxy acetals.

The wood pyrolysis is attractive because forest and industrial wood residues can be readily converted into liqtrid products. These liqtrids, as erode bio-oil or slurry of charcoal of water or oil, have advantages in transport, storage, combustion, retrofitting and flexibility in production and marketing (Demirbas, 2007). In the first step of pyrolysis of carbohydrates dehydration occtrrs and at low temperatures dehydration predominates. Dehydration is also known as a char-forming reaction. Between 550 and 675 K volatile products, tar, and char are formed. The volatile products are CO, CO, H O, acetals, furfural, aldehydes and ketones. Levoglucosan is the principle component in tar. 

Whereas the pATa for the a-protons of aldehydes and ketones is in the region 17-19, for esters such as ethyl acetate it is about 25. This difference must relate to the presence of the second oxygen in the ester, since resonance stabilization in the enolate anion should be the same. To explain this difference, overlap of the non-carbonyl oxygen lone pair is invoked. Because this introduces charge separation, it is a form of resonance stabilization that can occur only in the neutral ester, not in the enolate anion. It thus stabilizes the neutral ester, reduces carbonyl character, and there is less tendency to lose a proton from the a-carbon to produce the enolate. Note that this is not a new concept we used the same reasoning to explain why amides were not basic like amines (see Section 4.5.4). 

Because carbohydrates are so frequently used as substrates in kinetic studies of enzymes and metabolic pathways, we refer the reader to the following topics in Ro-byt s excellent account of chemical reactions used to modify carbohydrates formation of carbohydrate esters, pp. 77-81 sulfonic acid esters, pp. 81-83 ethers [methyl, p. 83 trityl, pp. 83-84 benzyl, pp. 84-85 trialkyl silyl, p. 85] acetals and ketals, pp. 85-92 modifications at C-1 [reduction of aldehydes and ketones, pp. 92-93 reduction of thioacetals, p. 93 oxidation, pp. 93-94 chain elongation, pp. 94-98 chain length reduction, pp. 98-99 substitution at the reducing carbon atom, pp. 99-103 formation of gycosides, pp. 103-105 formation of glycosidic linkages between monosaccharide residues, 105-108] modifications at C-2, pp. 108-113 modifications at C-3, pp. 113-120 modifications at C-4, pp. 121-124 modifications at C-5, pp. 125-128 modifications at C-6 in hexopy-ranoses, pp. 128-134. 

Leonard NM, Oswald MC, Freiberg DA, Nattier BA, Smith RC, Mohan RS (2002) A simple and versatile method for the synthesis of acetals from aldehydes and ketones using bismuth triflate. J Org Chem 67 5202-5207... 

It has now been found that further extension of this reaction to ketone acetals and a wide range of aldehydes and ketones is possible when catalytic amounts of zinc chloride are added to the reaction mixture. The catalyzed reaction generally proceeds at room temperature and usually gives good yields of 2,2-alkoxyoxetanes (equation 100). This appears to be the method of choice for such compounds, since it is highly regiospecific, whereas the photochemical addition of aldehydes or ketones to ketene acetals is not (77JOC3128). 

Since 1895, when Emil Fischer1 described the reaction of aldehydes and ketones with glycoses, an impressive part of the chemistry of carbohydrates has dealt with acetals, and especially cyclic acetals (mainly 1,3-dioxolanes and 1,3-dioxanes). There are probably relatively few studies on the synthetic chemistry of monosaccharides that do not describe at least one acetal of a carbohydrate, be it for routine protection, or for use in an original synthesis. At least, in this Series, three articles have appeared on the cyclic acetals of the aldoses and aldosides2,3 and of the ketoses4, one article dealt with acetals of tetri-... 

CA 68, 41780b(1968) [Thickeners (such as homopolymers and copolymers of unsatd acids, ketones acetals) for liquid expls (such as NG) are discussed. For example, lOg of a 40% soln of poly(vinylacetate) in EtOAc was mixed with 90g NG and after evapn of EtOAc on a water baih, a clear, homogeneous viscous soln was formed. Condensation products of aldehydes and ketones and of diols and... 

The stoichiometric equivalents of halofluorides have been recently applied to transform alkylene dithioacetals into gcm-difluorides.70-71 Dithioacetals such as 1,3-dithiolanes and 1,3-dithianes arc readily obtained from the corresponding carbonyl compounds by the reaction with ethane-1,2-dithiol or propane-1,3-dithiol in the presence of the complexes boron trifluoride-bis(acetic acid) or boron trifluoride-diethyl ether. Using a two-step procedure, a range of aldehydes and ketones can be converted into gem-difluorides under mild conditions. 

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