Acetalization of aldehydes

The oxidation of terminal alkenes with an EWG in alcohols or ethylene glycol affords acetals of aldehydes chemoselectively. Acrylonitrile is converted into l,3-dioxolan-2-ylacetonitrile (69) in ethylene glycol and to 3,3-dimetho.xy-propionitrile (70) in methanol[28j. 3,3-Dimethoxypropionitrile (70) is produced commercially in MeOH from acrylonitrile by use of methyl nitrite (71) as a unique leoxidant of Pd(0). Methyl nitrite (71) is regenerated by the oxidation of NO with oxygen in MeOH. Methyl nitrite is a gas, which can be separated easily from water formed in the oxidation[3]. 

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... 

N-Acetals of aldehydes can be readily prepared by reaction of aldehydes with tri-methylsilylated secondary amines. Thus, formaldehyde is converted by diethylami-notrimethylsilane 146, in 55% yield, into the silylated 0,N-acetal 422, which reacts with a further equivalent of 86 to give 90% of the N,N-acetal 423 and 94% hexa-methyldisiloxane 7 [41, 42]. On heating of diethylamine with formaldehyde and HMDS 2, 22% 422, 70% of the N,N-acetal 423, HMDSO 7, and ammonia are obtained [42] (Scheme 5.10). 

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],... 

Acetals of aldehydes such as benzaldehyde dimethyl acetal 121 are readily reduced by trimethylsilane 84a [213] or triethylsilane 84b in the presence of TMSOTf 20... 

The acid-catalyzed acetalation of aldonolactones with alkyl acetals of aldehydes or ketones takes place, in some instances, with esterification of the lactone group to give acetal derivatives of alkyl aldonates (11,22). 

Acetals of aldehydes are usually stable to lithium aluminum hydride but are reduced to ethers with alane prepared in situ from lithium aluminum hydride and aluminum chloride in ether. Butyraldehyde diethyl acetal gave 47% yield of butyl ethyl ether, and benzaldehyde dimethyl acetal and diethyl acetal afforded benzyl methyl ether and benzyl ethyl ether in 88% and 73% yields, respectively [792]. 

The polar properties of the alpha-C-H bonds and their reactivity towards hydrogen atom abstraction in acetals are enhanced by the presence of two ether groups. These hydrogens are susceptible to abstraction by excited carbonyl compounds (77). Cleavage of C—0 bonds in acetals occurs readily when an acetal radical is formed (38) even at room temperature. It has been shown that irradiation of cyclic acetals of aldehydes at room temperature in the presence of acetone leads to the appropriate carboxylic esters (22),... 

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). 

Acetals of ketones hydrolyse faster than acetals of aldehydes,... 

Under the reaction conditions for alkylidenation, compounds containing the following functional groups were found to be stable trimethylsilyl ethers of alcohols, olefins, primary alkyl iodides, and ethylene acetals of aldehydes. 

Some terminal alkenes are oxidized to aldehydes depending on their structure. As described before, acrylonitrile and acrylate are oxidized to acetals of aldehydes in alcohols or ethylene glycol.Selective oxidation of terminal carbons in 4-hydroxy-1-alkenes (18) gave the five-membered hemiacetals (19), which can be converted to y-butyrolactones by PCC oxidation (Scheme 4). Formation of a tricyclic six-membered hemiacetal (62%) from a 5-hydroxy-1-alkene system was used for the synthesis of rosa-ramicin. Formation of aldehydes as a major product from terminal alkenes using (MeCN)2Pd(Cl)(N02) and CuCU in r-butyl alcohol under selected conditions was reported. The vinyl group in the -lactam was oxidized mainly to the aldehyde as shown below (equation 12). ... 

Acetals Various lanthanide chlorides are efficient catalysts for acetalization of aldehydes by methanol. Lanthanum chloride and cerium chloride are satisfactory for aliphatic aldehydes, but erbium chloride and ytterbium chloride are generally superior, particularly for aromatic and bicyclic aldehydes. Addition of trimethyl orthoformate as a water scavenger allows use of the commerically available hydrated forms of the salts. Acetals can be obtained in 80-100% yield from reactions conducted for 10 minutes at 25°. 

Bromination of enol acetates of aldehydes with subsequent reaction of the brominated product with methanol furnishes a novel synthesis of a-bromoaldehyde acefbls. 

Carboxy includes carboxy (carboxylic acids), alkoxycarbonyl (esters), carbamoyl (amides), thiocarbamoyl, hydrazinocarbamoyl (hydrazides), guanidinocarbonyl, azidocarbonyl (azides), chlorocarbonyl (acid chlorides), amidino, C-hydrazino-C-iminomethyl, C-alkoxy-C-iminomethyl (imino ethers), C-alkylthio-C-iminomethyl (iminothioethers), cyano (nitriles), C-formyl(aldehydes), dialkoxymethyl (acetals of aldehydes), C-acyl (ketones), isocyanato, and thiocyanato groups. 

Acetals of aldehydes are converted into esters by the action of ozone [111] or peroxy acids [277, 327], Butyraldehyde diethylacetal, when treated for 30 min with peroxy acetic acid and sulfuric acid as a catalyst, furnishes ethyl butyrate in a 69% yield after 11 h at 40 °C [277]. Enanthaldehyde (heptanal) dimethyl acetal reacts with ozone in dichloromethane at -78 °C for 15 h or at room temperature for 1.5 h to produce methyl heptanoate in 90% yield (equation 369) [111]. 

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 >. 

Review. Huang1 has reviewed the synthetic use of organoantimony compounds. In addition to Wittig-typc reactions., his laboratory has reported several novel uses for these compounds such as a selective acetalization of aldehydes (equation 1). Acetalization can also be effected by the system SbCl.i/AI and an alcohol in almost quantitative yield. 

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

Most ketals are hydrolysed instantaneously by very dilute acid. Cyclic acetals and ketals are relatively stable, as are acetals of aldehydes containing basic groups. Hydrolysis of the last-mentioned class may lead to aldol condensation or formation of the Schiff base, so that concentrated acids are used in such cases. 

When acetals of aldehydes or ketones are heated with thiols in a bomb tube at 100-130° the OR groups are replaced by SR, this process having been used to provide acetaldehyde diethyl mercaptal (84% yield), acetone diethyl mercaptol (81%), and triethyl trithioorthoformate (87%).425... 

Aldehyde synthesis. Japanese chemists have reported a synthesis of dimethyl acetals of aldehydes (3) by alkylation of the lithium salt of (1) with an alkyl iodide followed by hydrolysis of the resulting 1-methylthioalkyl N,N-dimethyldithiocarbamate (2) with mercuric oxide and mercuric chloride in methanol. 

Initial rates and conversion for the acetalization of aldehydes 1, 2 and 3 with trimethyl orthoformate (TMOF) over different acid catalysts . 

Dioxepanes (1) have usually been prepared by direct acetalization of aldehydes or ketones with 1,4-diols in the presence of an acid <72GEP(0)2059704, 83CC705, 85JCS(Pl)2093, 92GEP(O)4i044il,... 

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. 

Several efficient oxidation reactions with molecular oxygen were developed using transition-metal complexes coordinated by variuos ligands in combination with apprOTriate reductants. Recently, it was found that cyclic ketones such as 2-methylcyclohexanone and acetals of aldehyde such as propionaldehyde diethyl acetal were effectively employed in aerobic epoxidation of olefins catalyzed by cobalt(II) complexes. In the latter case, ethyl propionate and ethanol were just detected in nearly stoichiometric manner as coproducts (Scheme 12), therefore the reaction system is kept under neutral conditions during the epoxidation. 

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