Glycols 1.3- dioxolanes

The kinetics of the aqueous formaldehyde-ethylene glycol-1,3-dioxolane system have been investigated, including its acid catalysis.4... 

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]. 

Reactions with Alcohols, Mercaptans, and Phenols. Alcohols add readily to acetaldehyde in the presence of trace quantities of mineral acid to form acetals eg, ethanol and acetaldehyde form diethyl acetal [105-57-7] (65). Similarly, cycHc acetals are formed by reactions with glycols and other polyhydroxy compounds eg, ethylene glycol [107-21-1] and acetaldehyde give 2-methyl-1,3-dioxolane [497-26-7] (66) ... 

Ketones and aldehydes react with ethylene glycol under acidic conditions to form 1,3-dioxolanes (cychc ketals and acetals) (eq. 7). 

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). 

Perchloric acid (79% HCIO4/CH2CI2, 0°, 1 h 25°, 3 h, 87% yield) and periodic acid (aq. dioxane, 3 h, quant, yield) cleave 1,3-dioxolanes the latter drives the reaction to completion by oxidation of the ethylene glycol that forms. Yields are substantially higher from cleavage with perchloric acid (3 AHCIO4/THF, 25°, 3 h, 80% yield) than with hydrochloric acid (HCl/HOAc, 65% yield)... 

This dioxolane is readily formed from the glycol (TsOH, benzene, reflux, 70-95% yield) it is cleaved by irradiation (350 nm, benzene, 25°, 6 h, 75-90% yield). This group is stable to 5% HCl/THF 10% AcOH/THF 2% oxalic acid/THF 10% aq. H2SO4/THF 3% aq. TsOH/THF. ... 

CF3C02)2lPh, H2O, CH3CN, 85-99% yield.In the presence of ethylene glycol the dithiane can be converted to a dioxolane (91% yield). The reaction conditions are not compatible with primary amides. Thioesters are not affected. 

The saturated 3-ketone can also be protected as the ethylene ketal, which is prepared directly by reaction with ethylene glycol or by exchange dioxo-lanation. Selective formation of 3-ethylenedioxy compounds is also possible, but the former method is not particularly effective in the presence of 6-, 17- or 20-ketones. However, the exchange dioxolanation technique is more sensitive to steric effects and good selectivity at C-3 can be achieved in the presence of a 17-ketone, provided the reagent does not contain glycol. ... 

A"" -3-Ketones are more reactive than cross-conjugated A ""-3-ketones. A"" -3,3-CycIoethylenedioxy compounds can be easily prepared by acid-catalyzed reaction with ethylene glycol or by exchange dioxolanation. 3,3-Cycloethylenedioxy-A -dienes can be prepared from 3,3-cycloethy-lenedioxy-A -enes by allylic bromination and dehydrobromination. Acid hydrolysis yields A"" -3-ketosteroids. ... 

Ethylene ketals can be readily prepared by the ethylene glycol technique. 6-Ethylene ketals can also be prepared by exchange dioxolanation and suitable conditions have been described for the preparation of either the 3-mono-ketal (78), the 3,6-diketal (79) or 3,6,17-triketal (80) from the triketone... 

Unsubstituted 20-ketones undergo exchange dioxolanation nearly with the same ease as saturated 3-ketones although preferential ketalization at C-3 can be achieved under these conditions. " 20,20-Cycloethylenedioxy derivatives are readily prepared by acid-catalyzed reaction with ethylene glycol. The presence of a 12-ketone inhibits formation of 20-ketals. Selective removal of 20-ketals in the presence of a 3-ketal is effected with boron trifluoride at room temperature. Hemithioketals and thioketals " are obtained by conventional procedures. However, the 20-thioketal does not form under mild conditions (dilution technique). ... 

Hydrogenation of enones in MeOH with Pd/C resulted in acetal formation. When ethylene glycol/THF is used as solvent, the related dioxolane is formed in 86% yield. 

CF,C02)2lPh, H2O, CH3CN, 85-99% yield. In the presence of ethylene glycol the dithiane can be converted to a dioxolane (91% yield) or in the presence of methanol to the dimethyl acetal. The reaction conditions are not compatible with primary amides. Thioesters are not affected. A phenylthio ester is stable to these conditions, but amides are not. The hypervalent iodine derivative l-(t-butylperoxy)-l,2-benziodoxol-3(l/f)-one similarly cleaves thioketals."... 

Dioxolane derivatives, which are obtained from methoxybutenone and glycols and used as antifungicides, and squalene synthetase inhibitors have been described (94MI1). The reactions of mono- and oligosaccharides with... 

A slightly more complex anti arrhythmic agent is pi rmentol (74). It is synthesized from 4-chloropropiophenone (72) by keto group protection as the dioxolane (with ethylene glycol and acid) followed by sodium iodide-mediated alkylation with cis 2,6-dimethyl pi peri dine to give 7. Deblocking with acid followed by addition of 2-1ithiopyridine completes the synthesis of pi rmentol (74). 

A detailed spectroscopic and theoretical study of the conformation of dioxolanes 1 has appeared <96T8275>, and a theoretical study has shown that the anomeric effect explains the non-planarity of 1,3-dioxole <96JA9850>. The tetraalkynyldioxolanone 2 has been prepared and its structure and reactivity studied <96HCA634>. Both enantiomers of the chiral glycolic acid equivalent 3 can be prepared from D-mannitol <96HCA1696>, and lipase-mediated kinetic... 

Reaction of ketones such as 1-menthone 398 with silylated glycolic acid 417 in the presence of catalytic amounts of TMSOTf 20 provides an lil-mixture of the l,3-dioxolan-4-ones 418 and 419 [35, 36]. Likewise, other aldehydes and ketones [37, 38] and pivaldehyde [39] react with substituted silylated glycohc adds 420 a, b and yS-hydroxy acids 420c to give, e.g., 421 a, b and 421c as mixtures [37-40]. Reaction of pivaldehyde with the persilylated hydroxy acid 420 d and TMSOTf 20 to... 

Also, 1,3-dioxolane was obtained from the reaction of ethylene glycol (EG) and aqueous formaldehyde in high yield using an ion-exchange resin catalyst. In a batch mode of operation, with 50% excess EG, the conversion of formaldehyde is limited to 50% due to equilibrium limitation, whereas in batch reactive distillation, formaldehyde conversion greater than 99%... 

Conversion to acetals is a very general method for protecting aldehydes and ketones against nucleophilic addition or reduction.245 Ethylene glycol, which gives a cyclic dioxolane derivative, is frequently employed for this purpose. The dioxolanes are usually prepared by heating a carbonyl compound with ethylene glycol in the presence of an acid catalyst, with provision for azeotropic removal of water. 

Accordingly, the cyclopropenylidene anthrones 190/198 were converted by ferric chloride in hydroxylic solvents to the allene ketal 466, whose hydrolysis gives the allenic ketone 46 7288. The dioxolane 468 was obtained from the alkyl-substituted quinocyclopropene 190 in glycol and the ketone 467 in methanol. Apparently FeCl3 served not only as an oxidant, but also as a Lewis acid assisting solvent addition to C1 2 of the triafulvene. 

A mixture of an aldehyde or a ketone with ethylene glycol (EG) and p-toluenesulfo-nic acid (pTSA) leads to the corresponding dioxolane, after irradiation [61] (Scheme 8.42). 

Fahey (16) suggests that intermediate 3 dissociates formaldehyde he finds supportive evidence in the rhodium-based system by observation of minor yields of 1,3-dioxolane, the ethylene glycol trapped acetal of formaldehyde. For reasons to be discussed later, we believe the formation of free formaldehyde is not on the principal reaction pathway. (c) We have also rejected two aspects of the reaction mechanism proposed by Keim, Berger, and Schlupp (15a) (i) the production of formates via alcoholysis of a formyl-cobalt bond, and (ii) the production of ethylene glycol via the cooperation of two cobalt centers. Neither of these proposals accords with the observed kinetic orders and the time invariant ratios of primary products. 

Chiral glycolates. The chiral dioxolanes 1 and 2 are prepared by reaction of 8-phenylmenthone with a protected derivative, (CH3)3SiOCH2COOSi(CH3)3, of glycolic acid catalyzed by trimethylsilyl triflate. They are obtained in about a 1 1 ratio and are separable by chromatography. Alkylation of the enolates of 1 and 2 proceeds with marked diastereofacial selectivity. After separation of the major... 

The reason that OH does not attack the u-carbon in 63, in contrast to the reaction in Eq. (17), would be due to the stronger electron donation by the /3-carbon in 63, which increases the electron density at the a-carbon atom. Addition of ethylene glycol vinyl ether to the p-toluenesulfonate salt of 64 in CDC13 catalytically yields 2-methyl-1,3-dioxolane (Eq. (18)). The reaction proceeds almost instantaneously, and a 50-fold equivalent of the substrate is completely converted to 2-methyl-1,3-dioxolane, which was confirmed by -NMR. After the reaction, the Pt(III) dimer complex without alkyl ligand is left in the solution, which is still capable of catalysis. The reaction is shown as Eq. (18). 

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