Acetals, mixed

Oxidation. Acetaldehyde is readily oxidised with oxygen or air to acetic acid, acetic anhydride, and peracetic acid (see Acetic acid and derivatives). The principal product depends on the reaction conditions. Acetic acid [64-19-7] may be produced commercially by the Hquid-phase oxidation of acetaldehyde at 65°C using cobalt or manganese acetate dissolved in acetic acid as a catalyst (34). Liquid-phase oxidation in the presence of mixed acetates of copper and cobalt yields acetic anhydride [108-24-7] (35). Peroxyacetic acid or a perester is beheved to be the precursor in both syntheses. There are two commercial processes for the production of peracetic acid [79-21 -0]. Low temperature oxidation of acetaldehyde in the presence of metal salts, ultraviolet irradiation, or osone yields acetaldehyde monoperacetate, which can be decomposed to peracetic acid and acetaldehyde (36). Peracetic acid can also be formed directiy by Hquid-phase oxidation at 5—50°C with a cobalt salt catalyst (37) (see Peroxides and peroxy compounds). Nitric acid oxidation of acetaldehyde yields glyoxal [107-22-2] (38,39). Oxidations of /)-xylene to terephthaHc acid [100-21-0] and of ethanol to acetic acid are activated by acetaldehyde (40,41). 

A mixed acetal of benzaldehyde, methanol, and salicylic acid has also been studied. It, too, shows a marked rate enhancement attributable to intramolecular general acid catalysis ... 

Enol ethers (15) and mixed acetals (16) are readily obtained from secondary but not from tertiary alcohols, whereas tetrahydropyranyl ethers can be formed even from tertiary alcohols. This is a result of the greater steric requirements of the reagents (17) and (18) as compared to (19). 

Symmetrical labile ethers such as cycloalkenyl ethers (15) or mixed acetals (16) can also be prepared from the 3-hydroxyl group by acid-catalyzed exchange etherification or by acid-catalyzed addition to cyclohexanone methyl enol ether. 

Beta- and 3a-alcohols of the 5)5- and 5a-series respectively also form tetrahydropyranyl ethers, cycloalkenyl ethers and mixed acetals. ... 

The hindered 11 )5-hydroxyl group fails to react with dihydropyran. However, mixed acetals [e.g., methoxymethyl ether (97)] and hemiacetals e.g., hydroxymethyl ether (98)] are obtained as by-products in the formation of the BMD group. ... 

Formation of an 11-methoxybenzyl ether occurs in satisfactory yield during the preparation of a 17,21 -benzylidene derivative [e.ff., (26)]. The usefulness of this ether and of related mixed acetals in removing the inhibitory effect of the 11 j5-hydroxyl group on the 20-ketone reduction has been reported. ... 

The tertiary 17) -hydroxyl group does not form bulky enol ethers and mixed acetals. However, tetrahydropyranyl ethers are obtained from 17a-ethynyl-17]3-hydroxy compounds. Tetrahydropyranyl ethers have also been prepared from tertiary 17a-hydroxyl groups. ... 

The 21-hydroxyl group in the corticosteroid series can be protected as the base stable triphenylmethyl ether and tetrahydropyranyl ether. " " Mixed acetals from 21-alcohols are extremely acid sensitive compounds. ... 

ORGANIC REACTIONS IN STEROID CHEMISTRY 7. Mixed Acetals... 

Structurally, 0-glycosides are mixed acetals that involve the anomeric position of furanose and pyranose forms of carbohydrates. Recall the sequence of intermediates in acetal formation (Section 17.8) ... 

The dithioacetal can be converted to an 0,5-acetal."" The mixed acetals were then used to prepare furanosides. 

Contained within intermediate 25 is an acid-labile mixed acetal group and it was found that treatment of 25 with camphorsulfonic acid (CSA) results in the formation of dioxabicyclo[3.3.0]octane 26 in 77 % yield. Acid-induced cleavage of the mixed cyclic acetal function in 25, with loss of acetone, followed by intramolecular interception of the resultant oxonium ion by the secondary hydroxyl group appended to C leads to the observed product. Intermediate 26 clearly has much in common with the ultimate target molecule. Indeed, the constitution and relative stereochemistry of the dioxabicyclo[3.3.0]octane framework in 26 are identical to the corresponding portion of asteltoxin. 

The first total synthesis of the marine dolabellane diterpene (+)-4,5-deoxy-neodolabelline (70) was accomplished by D. R. Williams et al. [58]. The trans-disubstituted dihydropyran moiety in key intermediate 69 was efficiently prepared from mixed acetal 66 by RCM with second-generation catalyst C and subsequent Lewis acid-catalyzed allylation of ethyl glycosides 67 with allylsi-lane 68 (Scheme 12) [59]. 

Glycosides are mixed acetals formally arising by elimination of water between the hemiacetal or hemiketal hydroxy group of a sugar and a hydroxy group of a second compound. The bond between the two components is called a glycosidic bond. 

Glycosides were originally defined as mixed acetals (ketals) derived from cyclic forms of monosaccharides. 

The conversion of vicinal azido selenides into tetrahydrofiirans by PhSeOTf in MeCN at room temperature is reported <96JOC7085>. 3-Butadienyl tetrahydrofiirans and a-butadienyl y-butyrolactones can be prepared by radical cyclization of P-bromopent-4-en-2-ynyl ethers and mixed acetals <96SL391>. The total synthesis of trilobacin was reported <96JOC7642>. 

DMSO or other sulfoxides react with trimethylchlorosilanes (TCS) 14 or trimefhylsilyl bromide 16, via 789, to give the Sila-Pummerer product 1275. Rearrangement of 789 and further reaction with TCS 14 affords, with elimination of HMDSO 7 and via 1276 and 1277, methanesulfenyl chloride 1278, which is also accessible by chlorination of dimethyldisulfide, by treatment of DMSO with Me2SiCl2 48, with formation of silicon oil 56, or by reaction of DMSO with oxalyl chloride, whereupon CO and CO2 is evolved (cf also Section 8.2.2). On heating equimolar amounts of primary or secondary alcohols with DMSO and TCS 14 in benzene, formaldehyde acetals are formed in 76-96% yield [67]. Thus reaction of -butanol with DMSO and TCS 14 gives, via intermediate 1275 and the mixed acetal 1279, formaldehyde di-n-butyl acetal 1280 in 81% yield and methyl mercaptan (Scheme 8.26). Most importantly, use of DMSO-Dg furnishes acetals in which the 0,0 -methylene group is deuter-ated. Benzyl alcohol, however, affords, under these reaction conditions, 93% diben-zyl ether 1817 and no acetal [67]. 

It had been decided to purify N,N-dimethylaniline by mixing acetic anhydride, water and hydrochloric acid following a published operating method. However, a slight modification was made that consisted in using the double amount of reagents. The medium was cooled with ice. When hydrochloric acid was introduced, the anhydride hydrolysis was so violent that it caused the apparatus to detonate. 

Carbonyl-ene reactions can be carried out in combination with other kinds of reactions. Mixed acetate acetals of y,8-enols, which can be prepared from the corresponding acetate esters, undergo cyclization with nucleophilic capture. When SnBr4 is used for cyclization, the 4-substituent is bromine, whereas BF3 in acetic acid gives... 

Radical cyclization reactions have been extensively applied in synthesis. Among the first systems to be studied were unsaturated mixed acetals of bromoacetaldehyde.323... 

Favored reaction at HO-5 in uridine 3 -phosphate through the formation of a mixed acetal of an aliphatic aldehyde with another alcohol has been claimed, but product isolation required chromatography on cellulose, and the yield reported343 was low ( 23%). 

Lab experiment 98085 showed that mixing acetic acid and water is endothermic at room temperature. 

Cyclization of mixed acetals (13,300).4 This reaction is a particularly useful route to eight-membered cyclic ethers (oxocanes) and provides the first practical route to a natural oxocene, (- )-laurenyne (3), from an optically active mixed acetal 1. Thus cyclization of 1 followed by O-desilylation affords 2 as the only cyclic product. Remaining steps to 3 involved C-desilylation, for which only HF/pyridine is useful, introduction of unsaturation into the C2-side chain, and extension of the C8-side chain. Exploratory studies showed that unsaturation at the p- or y-positions to the cite of cyclization of 1 prevent or retard cyclization with a wide variety of Lewis acids. The cyclization is apparently more tolerant of substitution in the terminator position, C3-Q, of the oxocene. 

The stereochemical issue of the acetalic carbon was subsequently addressed. Specifically, two diastereomers are possible at the stage of mixed acetal formation. Quite remarkably, the formation of mixed acetal proved to be highly selective to give almost exclusively the S-diastereomer. Mixed acetals with various substitution patterns were synthesized and uniformly stereoseletive formation of S-isomers was observed in each case (Scheme 7.21).73... 

E 472f Mixed acetic and tartaric acid esters of mono- and diglycerides of fatty acids... 

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