Diketene, hydrolysis

Water hydroly2es pure diketene only slowly to give acetoacetic acid [541-50-4] which quickly decomposes to acetone and carbon dioxide, but increasing the pH or adding catalysts (amines, palladium compounds) increases the rate of hydrolysis. The solvolysis of diketene in ammonia results in aceto acetamide [5977-14-0] if used in stoichiometric amounts (99), and P-arninocrotonarnide [15846-25-0] if used in excess (100). 

Initial polymer hydrolysis products are the diol or mixture of diols used in the reaction with the diketene acetal, and pentaerythritol dipropionate, or diacetate if 3,9-bis(methylene-2,4,8,10-tetraoxaspiro-[5,5Jundecane) was used. These pentaerythritol esters hydrolyze at a slower rate to pentaerythritol and the corresponding aliphatic acid (13). 

However, in subsequent work it was found that carboxylic acid groups readily add to ketene acetals to form carboxyortho ester linkages (24). These are very labile linkages and on hydrolysis regenerate the carboxylic acid group which then exerts its catalytic function. Because carboxylic acids add so readily to ketene acetals, very labile polymers can be prepared by the addition of diacids to diketene acetals. The utilization of such polymers is currently under investigation. 

The enamines 199 and 191, prepared by condensation of tropinone (124) with piperidine and morpholine, respectively, have proved to be useful synthetic intermediates 98,108). Addition of acrylonitrile to enamine 199, followed by hydrolysis, produced cyanoethyltropinone (200) in 43% yield 108) (Scheme 21). The reaction of the enamine 191 with diketene permitted the preparation of isobellendine (114) vide supra) in 53% yield 98). 

The second method of forming the oxazin-3-one ring is illustrated by reaction of 363 with diketene 364 followed by diazo exchange, base hydrolysis, and Lewis acid-catalyzed cyclization to give 365 as shown in Scheme 43. This method has been used in fewer reports <1983JOC2675, 1983EPP80117, 1984USP4431167>. 

Solid-phase synthesis of pyrido[2,3 pytirtiidines 514 was achieved by Hantzsch condensation of Wang resin-supported Knoevenagel derivative 513 with 6-aminouracil derivatives 512 as an a-oxo enamine component in the presence of ceric ammonium nitrate (CAN) in DMA followed by hydrolysis with TFA in CH2GI2. Compound 513 was prepared by treatment of a hydroxylated polymer, such as Wang or Sasrin resin, with diketene, followed by condensation with benzaldehyde (Equation 41) <1996TL4643>. 

In another cyclization procedure for the 1,5-benzodiazodne system, the nitriles (296) are converted to the aminodihydrodiazocines (297) (79CPB2589). Attack of nucleophiles on (297) occurs at the N-5—C-6 bond to give the 3,4,5,6-tetrahydrodiazodnes (298) with NaBH4 and the jS-aminoethylquinazolines (301) on hydrolysis. The diazocines (297) behave as typical amidines. Oxidation leads to the amidoximes (300) which on hydrolysis are converted to 2,1-benzisoxazoles (302), and reaction with diketene leads to the fused pyrimidinones (299 and l-methyl-3-one isomer) (79CPB2927). 

Amino-3-cyanofurans (307) are obtained by base catalyzed condensation of the acyloins (306) with malonodinitrile, and on acid hydrolysis yield the butenolides (308) (Scheme 80) (66CB1002). Diketene and an isocyanide react to give the lactone (309) in the presence of a tertiary base (73GEP2222405). When diphenylketene is treated with bis(cycloocta-l,5-diene)nickel and pyridine, the complex Ni(py)2(Ph2C=CO)2 is formed which is converted into compound (310) by carbon monoxide (78JOM(l52)C29). 

Keto stannylenolates can be prepared by the reaction of Sn-O or Sn-N bonded compounds with diketene, which can be regarded as a cyclic enol ester. The adducts formed from bis(tributyltin) oxide can undergo further reaction, with subsequent decarboxylation, to give the same products as those from the simple enolates. Alkylation with alkyl iodides or benzyl or allyl bromides is strongly catalysed by lithium bromide (e.g. Scheme 14-5). Double alkylation can be achieved with HMPA as solvent.120 The product of alkylation before the final hydrolysis is itself a tin enolate, which can be used in reactions with further carbon electrophiles. 

Very recently, homochiral 3-hydroxyethylazetidinones have been obtained by asymmetric hydrolysis of racemic precursors. Cycloaddition of diketene with in situ prepared V-anisyl propargylaldimine afforded dl-trans azetidinone 96... 

This reaction was first reported by Blomquist in 1947. It is the reaction to form intermediate to macrocyclic ketones via the process of intramolecular condensation of aliphatic diketenes at diluted concentration followed by hydrolysis and decarboxylation of cyclic ketene derivatives. The intermolecular condensation of diketenes will form even larger macrocyclic diketones, which can be converted into simple macrocyclic diketones." The ketene can be easily obtained by the treatment of acyl chloride of dicarboxylic acid with tertiary amines, of which triethylamine gives the best result. Although some polyketene products also form in this process, they can be easily removed. Other methods for preparing macrocyclic ketones include the Ziegler, Hunsdiecker, Ruzicka, and Glinski reactions. 

Asymmetric Buchner reactions using chiral auxiliary have also been undertaken. The diazoketo substrate 126 for the chiral tethered Buchner reaction is prepared from optically pure (2/ ,4/f)-2,4-pentanediol in three steps the Mitsunobu reaction with 3,5-dimethylphenol, esterification with diketene, and diazo formation/deacetylation. Treatment of 126 with rhodium(II) acetate results in a quantitative yield of 127 with more than 99% ee. This compound is reduced with lithium aluminium hydride, and the resulting diol 128 undergoes epoxidation and concurrent acetal formation to give 129 as a single diastereomer. Hydrogenation of 129 with Raney nickel proceeds stereoselectively to yield saturated diol 130, which is converted to aldehyde 132 via acid hydrolysis followed by oxidation. Compound 132 is a versatile intermediate for natural product synthesis. 

The acid-catalysed, neutral, and base-catalysed hydrolysis of seven lactones was studied using a hybrid supermolecule polarizable continuum model (PCM) approach including six explicit water molecules. DFT and ab initio methods were used to analyse the features of the various possible hydrolysis mechanisms of -propiolactone, j0-butyrolactone, j0-isovalerolactone, diketene, y-butyrolactone, 2(5//)-furanone, and... 

A second family of polyorthoesters, derived from the addition of polyols to di-ketene acetals without forming condensation by-products, was developed by SRI International (Scheme 4B). Initial work was conducted with the monomer, diketene acetal (3,9-bis(ethylidene-2,4,8,10-tetraoxaspiro[5,5]undecane, DETOSU), derived from pentaerythritol and 1,6-hexane diol. This reaction is exothermic and proceeds to completion virtually instantaneously. Then, the diketene acetal is reacted with a polyol to synthesize the polyorthoester. Here, the hydrolytic products are the diol and pentaerythritol dipropionate the further hydrolysis of this latter compound produces propionic acid, but no autocatalytic reaction is observed because this hydrolysis proceeds much more slowly than that of orthoester bonds. 

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