Dimethylacetal, hydrolysis

Treatment of (89) with lead tetraacetate generates the unstable open-ring aldehyde (90) which is quickly converted to a dimethylacetal (91). Following basic hydrolysis of the methyl ester and acetates, the acetal is cleaved with aqueous acid to produce TxB2. A number of other approaches, including one starting from the Corey aldehyde, have been described (58). 

The first synthesis of a cyclopropenone was reported in 1959 by Breslowls who achieved the preparation of diphenyl cyclopropenone (11) by reacting phenyl ketene dimethylacetal with benzal chloride/K-tert.-butoxide. The phenyl chloro carbene primarily generated adds to the electron-rich ketene acetal double bond to form the chlorocyclopropanone ketal 9, which undergoes 0-elimination of HC1 to diphenyl cyclopropenone ketal 10. Final hydrolysis yields 11 as a well-defined compound which is stable up to the melting point (120—121 °C). 

In a similar manner, coccinelline (99) and precoccinelline (100) have been synthesized from 2,6-lutidine (351) (336,450). Thus, treatment of the monolithium derivative (153) of 351 with P-bromopropionaldehyde dimethylacetal gave an acetal, which was converted to the keto acetal (412) by treatment with phenyllithium and acetonitrile. Reaction of 412 with ethylene glycol and p-toluenesulfonic acid followed by reduction with sodium-isoamyl alcohol gave the cw-piperidine (413). Hydrolysis of 413 with 5% HCl gave the tricyclic acetal (414) which was transformed to a separable 1 1 mixture of the ketones (415 and 416) by treatment with pyrrolidine-acetic acid. Reaction of ketone 416 with methyllithium followed by dehydration with thionyl chloride afforded the rather unstable olefin (417) which on catalytic hydrogenation over platinum oxide in methanol gave precoccinelline (100). Oxidation of 100 with m-chloroperbenzoic acid yielded coccinelline (99) (Scheme 52) (336,450). 

The analysis of essential fatty acids involves hydrolysis of the ester bonds and subsequent formation of the fatty acid methyl esters, which can be separated by gas chromatography (GC) [10]. By accident, the plasmalogens are hydrolysed in the same reaction and the methylation reaction transforms them into dimethylacetals, which appear in the GC run of the fatty acid methyl esters [4]. 

Fig. 21. Hydrolysis of acetals at 20°C on a Dowex 50W X10 resin catalyst [513]. Rate coefficients of the resin-catalysed reaction (feres) versus rate coefficients of the reaction catalysed by dissolved inorganic acid (fehom)- 1 Formaldehyde dimethylacetal 2, formaldehyde diethylacetal 3, formaldehyde di-2-propylacetal 4, acetaldehyde ethyleneacetal 5, acetone ethyleneacetal 6, acetaldehyde dimethylacetal 7, acetaldehyde diethylacetal. The slope for acetals 1—3 is 1, for the acetals 3—7 0.5.

An unequivocal synthesis of (637), protected as its A-2 -acetyl derivative (643), was successfully accomplished as shown in Scheme 3.140 [40]. Pyruval-dehyde dimethylacetal was first converted into its enamine (108). Condensation of (108) with the O-tosyl derivative of oximinomalononitrile gave the azadiene (638), which was converted to 2-amino-3-cyano-6-dimethoxymethyl-pyrazine (639) with ammonia. This latter compound was condensed with guanidine and the product (640) hydrolyzed first with base (to remove the 4-amino group) and then with acid to give pterin-7-carboxaldehyde (641). Acetylation of (641) followed by condensation with di-t-butyl p-aminobenzoyl-glutamate (235), reduction and hydrolysis gave (643). 

Methylglyoxalacetal (21) is obtained from acetone (39) by oxidation with methyl nitrite in the presence of methanol and an acid catalyst. Ethynylation and partial hydrogenation yield 2-hydroxy-2-methyl-but-3-enal-dimethylacetal (27), which, after acetylation, yields the P-formylcrotyl acetate (8 b)34 via a copper-catalyzed allyl rearrangement with subsequent hydrolysis. 

Compound (119) is a trioxadamantane derivative, which was prepared from the methanol adduct (6) of secologanin dimethylacetal (4a), in which all masked carbonyl groups were in acetal form. Aqueous acidic hydrolysis, under termodynamic control, transformed them groups of (6) into totally cyclized acetal structure. The backbone of the molecule has a high symmetry, which is broken by the functional groups [15]. 

A heterocycle intermediate is prepared by the condensation of 4-amino-6-chloro-ffj-benzene disulphonamide with urea which on treatment with methyl iodide in a basic medium yields the corresponding methylated heterocycle. This on hydrolysis in the presence of a base affords N-methylated aminosulphonamide which on condensation with dimethylacetal of 2,2,2-trifluoroethylmercaptoacetal-dehyde yields the official compound. 

An interesting method of indole C-4 substitution has been developed from a Claisen rearrangement. Reaction of 3-hydroxy-2-methoxyindoline (349) with W,A(-dimethylacetamide dimethylacetal gives the intermediate (350), which undergoes a Claisen rearrangement to yield a mixture of the 4-substituted indoline (351) and indole (352). The indoline can be converted into the indole by a sequence of methanol ehmination and base hydrolysis (Scheme 111) <(90CC78i). 

Various practical syntheses have been developed for the central carotenoid unit 8 [11]. One method developed at BASF (Scheme 2) starts with the addition of bromine to butadiene (14) in the gas phase, yielding a mixture of the dibromobutene isomers 75 and 16 which react with triethyl phosphite to produce f )-butene-l,4-diphosphonate (17) in virtually quantitative yield. After phosphonate condensation with methylglyoxal dimethylacetal (18) and hydrolysis of the intermediate Cio-bisacetal, crystalline 8 is obtained as an ( /Z)-mixture [12]. 

The first technical routes to 73 were based on methylglyoxal dimethylacetal 18 (Scheme 9) as a key intermediate [27]. The acetoxyaldehyde 73 was prepared in a five-step synthesis from 18 by successive acetylene addition, partial hydrogenation, acetylation, allylic rearrangement and hydrolysis of the acetal function (sequence 18- 80- 81 - 82 83 73). A particularly... 

Thiodiacetaldehyde bis(dimethylacetal) (265 g, 1.26 mol) was hydrolyzed in 700 mL hot water containing 12 mL cone. HCl. After completion of hydrolysis, the solution was cooled to 25°C, and 94 g methylamine hydrochloride (1.39 mol) and 220 g acetonedicarboxylic acid (1.51 mol) were added. The mixture was stirred, and solid K2CO3 was added slowly until the pH of the solution was 3.0. The clear solution was allowed to stand at room temperature in the dark, and the pH was held between 3.0 and 3.5 by the addition of hydrochloric acid after 2 h and after 7 h. After 24 h, the dark brown solution was acidified to pH 2 with... 

Exposure to mercury(II) bromide and 2,4collidine converted acetylated gly-cosyl halides to 1,2-orthoesters. Formation of orthoesters under kinetic control (ketene dimethylacetal, pTsOH, DMF) gave 4,6-derivatives 64-66 from d-glucose, D-mannose and methyl a-D-glucopyranoside, respectively, and product 67 from methyl 4,6-0-isopropylidene-a-D-mannopyranoside. Mild acid hydrolysis of 67 gave specifically the 2-0-acetate. This method has been applied to the selective acetylation of monoisopropylidenated furanoses an example is given in Scheme 3. ... 

The previously described 7-deazapurine carbocyclic nucleoside synthesis (see Scheme 1) indicated that the most efficient route to 22 would be via reaction of the protected chiral amine 23 with the dimethylacetal of 2-(2-amino-4,6-dichloropyrimidin-S yl)acetaldehyde followed by ring closure, hydrolysis and dqirotection. A review of the literature revealed two enantioselective routes to cyclobutyl derivatives that had been used in the chiral synthesis of carbocyclic oxetanocins and could be employed for preparing a precursor to 23. In one case, however, the initial step involved a [2-i-2]-cycloaddition reaction of not easily obtainable reagents in the presence of a chiral titanium compound as... 

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