Ketenes => carboxylic acids

Allene carboxylic acids have been cyclized to butenolides with copper(II) chloride. Allene esters were converted to butenolides by treatment with acetic acid and LiBr. Cyclic carbonates can be prepared from allene alcohols using carbon dioxide and a palladium catalyst, and the reaction was accompanied by ary-lation when iodobenzene was added. Diene carboxylic acids have been cyclized using acetic acid and a palladium catalyst to form lactones that have an allylic acetate elsewhere in the molecule. With ketenes, carboxylic acids give anhydrides and acetic anhydride is prepared industrially in this manner [CH2=C=0 + MeC02H (MeC=0)20]. 

Carboxylic acid anhydrides. A soln. of triflic anhydride in ethylene dichloride added dropwise to a soln. of Ph3PO in the same solvent at 0° under N2 after 15 min a soln. of / -toluic acid in ethylene dichloride added followed by EtjN, and stirred for 15 min - p-toluic anhydride. Y 93%. Redox side reactions are avoided, and ketones, esters and ethers unaffected. F.e. inch ketenes, carboxylic acid esters (incl. aryl esters) and amides, amidines from carboxylic acid amides, benzimidazoles, and intramolecular ar. acylation, also using N-diphenylphosphinyl-N -methylpiperazine (without the need for an additional base), s. J.B. Hendrickson, M.S. Hussoin, J. Org. Chem. 54, 1144-9 (1989) alternative prepn. of reagents cf. D. Crich, H. Dyker, Tetrahedron Letters 30, 475-6 (1989). 

Metalation and Reactivity with Electrophiles. The reaction of 2-(trimethylsilyl)thiazole (1) with carbon electrophiles such as aldehydes, ketones, ketenes, carboxylic acid chlorides, and azaaryl cations has attracted considerable attention. In this series, Nagasaki and coworkers reported the use of trimethylsilyl heteroarenes as the heteroarenyl carbanion donors in the electrophilic cyanation and described, for example, the electrophilic cyanation of 2-TST (1) with p-toluenesulfonyl cyanide in the absence of solvent (eq 25). ... 

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

KETENES, KETENE DITffiRS AND RELATED SUBSTANCES] (Vol 14) py-n-Octadecyloxy-3ymtrodiphenyl-p-carboxylic acid [21351-71-3]... 

Flash vacuum pyrolysis of 2-methoxycarbonylpyrrole (11) gives the ketene (12), characterized by IR absorption at 2110 cm. On warming to -100 to -90 °C the dimer (13) is formed (82CC360). Flash vacuum pyrolysis of indole-2-carboxylic acid (14) results in loss of water and the formation of a ketene (15) showing absorption at 2106 cm (82CC360). 

Unsubstituted 3-alkyl- or 3-aryl-isoxazoles undergo ring cleavage reactions under more vigorous conditions. In these substrates the deprotonation of the H-5 proton is concurrent with fission of the N—O and C(3)—-C(4) bonds, giving a nitrile and an ethynolate anion. The latter is usually hydrolyzed on work-up to a carboxylic acid, but can be trapped at low temperature. As shown by Scheme 33, such reactions could provide useful syntheses of ketenes and /3-lactones (79LA219). 

The methyl ester (100, R = CH3), derived from this A-nor acid by treatment with diazomethane, is different from the ester (102) obtained either by Favorskii rearrangement of 2a-bromo-5a-cholestan-3-one (101) or by the action of cyanogen azide on 3-methoxy-5a-cholest-2-ene (103) followed by hydrolysis on alumina. The ketene intermediate involved in photolysis of (99) is expected to be hydrated from the less hindered a-side of the molecule to give the 2j -carboxylic acid. The reactions which afford (102) would be expected to afford the 2a-epimer. These configurational assignments are confirmed by deuteriochloroform-benzene solvent shifts in the NMR spectra of esters (100) and (102). ... 

A. Reaction with Carboxylic Acid Chlorides, Anhydrides, and Ketenes 135... 

The final step is the reaction of the ketene with the solvent e.g. with water to yield the carboxylic acid 4 ... 

The preparation of a-iodocarboxylic acids is of particular interest, since iodide is a better leaving group as is chloride or bromide. A similar a-iodination with a phosphorus trihalide as catalyst is not known. However the iodination can be achieved in the presence of chlorosulfonic acid mechanistically the intermediate formation of a ketene 10 by dehydration of the carboxylic acid is assumed ... 

An a-diazo ketone 1 can decompose to give a ketocarbene, which further reacts by migration of a group R to yield a ketene 2. Reaction of ketene 2 with water results in formation of a carboxylic acid 3. The Woljf re arrangement is one step of the Arndt-Eistert reaction. Decomposition of diazo ketone 1 can be accomplished thermally, photochemically or catalytically as catalyst amorphous silver oxide is commonly used ... 

The ketocarbene 4 that is generated by loss of Na from the a-diazo ketone, and that has an electron-sextet, rearranges to the more stable ketene 2 by a nucleophilic 1,2-shift of substituent R. The ketene thus formed corresponds to the isocyanate product of the related Curtius reaction. The ketene can further react with nucleophilic agents, that add to the C=0-double bond. For example by reaction with water a carboxylic acid 3 is formed, while from reaction with an alcohol R -OH an ester 5 is obtained directly. The reaction with ammonia or an amine R -NHa leads to formation of a carboxylic amide 6 or 7 ... 

Acetylsultam 15 is also used for stereoselective syntheses of a-unsubstituted /1-hydroxy-carboxylic acids. Thus, conversion of 15 into the silyl-A/O-ketene acetal 16 and subsequent titanium(IV) chloride mediated addition to aldehydes lead to the predominant formation of the diastereomers 17. After separation of the minor diastereomer by flash chromatography, alkaline hydrolysis delivers /f-hydroxycarboxylic acids 18, with liberation of the chiral auxiliary reagent 1919. 

The photolysis of o-quinone diazides was carefully investigated by Stis in 1944, many years before the development of photoresists. Scheme 10-102 shows the photolysis sequence for the diazoquinone 10.75 formed in the diazotization of 2-amino-1-naphthol. The product of the photolytic step is a ketocarbene (10.76), which undergoes a Wolff rearrangement to a ketene (10.77). In the presence of water in-dene-3-carboxylic acid (10.78) is formed this compound is highly soluble in water and can be removed in the development step. The mechanism given in Scheme 10-102 was not postulated as such by Stis, because in 1944 ketocarbenes were unknown (for a mechanistic discussion of such Wolff rearrangements see review by Zollinger, 1995, Sec. 8.6, and Andraos et al., 1994). 

The method described here for the synthesis of [Pg.37]

The addition of water to enol ethers causes hydrolysis to aldehydes or ketones (10-6). Ketenes add water to give carboxylic acids in a reaction catalyzed by acids " ... 

Carboxylic acids can be dehydrated by pyrolysis, the product being a ketene ... 

Ketene itself is commercially prepared in this manner. Carboxylic acids have also been converted to ketenes by treatment with certain reagents, among them TsCl, ... 

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. 

Conversion of Free or Silylated Carboxylic Acids into Esters, Thioesters, Lactones, or Ketenes. Transesterification of Esters with Alcohols... 

Making use of the same reaction principle, disubstituted ketenes 66 have been reacted with aldehydes 80 to form p-lactones 81 [100], with diazo-compounds 82 to form 1,2-diazetidin-3-ones 83 [101] and with nitroso-compounds 84 to form 1,2-oxazetidin-3-ones 85 as precursors of a-hydroxy carboxylic acids (Fig. 42) [102],... 

The best yields are obtained when the ketene has an electronegative substituent, such as halogen. Simple ketenes are not very stable and must usually be generated in situ. The most common method for generating ketenes for synthesis is by dehydrohalo-genation of acyl chlorides. This is usually done with an amine such as triethylamine.167 Other activated carboxylic acid derivatives, such as acyloxypyridinium ions, have also been used as ketene precursors.168 Ketene itself and certain alkyl derivatives can be generated by pyrolysis of carboxylic anhydrides.169... 

The main synthetic application of the Wolff rearrangement is for the one-carbon homologation of carboxylic acids.242 In this procedure, a diazomethyl ketone is synthesized from an acyl chloride. The rearrangement is then carried out in a nucleophilic solvent that traps the ketene to form a carboxylic acid (in water) or an ester (in alcohols). Silver oxide is often used as a catalyst, since it seems to promote the rearrangement over carbene formation.243... 

Amides prepared from carboxylic acids and primary amines using azolides obtained from acid chloride/imidazolea) or ketene/imidazole systems.b)... 

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