Ketenes, preparation from anhydrides

Uses. The lowest member of this class, ketene itself, is a powerful acetylating agent, reacting with compounds containing a labile hydrogen atom to give acetyl derivatives. This reaction is used only when the standard acetylation methods with acetic anhydride or acetyl chloride [75-36-5] do not work weU. Most of the ketene produced worldwide is used in the production of acetic anhydride. Acetic anhydride is prepared from the reaction of ketene and acetic acid. 

Treatment of chromium (III) acetylacetonate with acetic anhydride and boron trifluoride etherate yielded a complex mixture of acetylated chelates but very little starting material. Fractional crystallization and chromatographic purification of this mixture afforded the triacetylated chromium chelate (XVI), which was also prepared from pure triacetylmethane by a nonaqueous chelation reaction (8, 11). The enolic triacetylmethane was prepared by treating acetylacetone with ketene. The sharp contrast between the chemical properties of the coordinated and uncoordinated ligand is illustrated by the fact that chromium acetylacetonate does not react with ketene. 

Acetic anhydride is prepared from distilled acetic acid by the ketene method with ethyl phosphate as a catalyst. The water from the first cyclonite wash on the vacuum filter contains on an average 20% of acetic acid which is recovered by extraction with ethyl acetate. 

The reduction of a-amino mixed anhydrides with lithium tri-/ert-butoxyaluminum hydride in THF at —70 °C is a very efficient method for synthesis of amino aldehydes (Table 9). 551 Three approaches were taken for the reduction of a-amino mixed anhydrides. 55 The first approach reduced Boc-Ala-OC02Et with lithium tri-terf-butoxyaluminum hydride was unsuccessful due to intramolecular rearrangements that gave Boc-Ala-OEt in addition to the Boc-Ala-H. The second approach involved reduction of diphenylacetic anhydride derivatives, which were prepared from Boc amino acids and diphenyl ketene, gave a diphenylacetic acid byproduct that was very difficult to remove unless the aldehyde was converted into its semicarbazone and separated chromatographically yields were 51-69%. The last and... 

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]. 

Acetaminophen, U5P. Acetaminophen. Af-Acetyl-p-aminophcnol. 4-hydroxyacetanilide. APAP (Panado. Tem-pra. Tylenol, etc.), may be prepared by reduction of p-ni-trophenol in glacial acetic acid, acetylation of p-aminophenol with acetic anhydride or ketene. or from p-hydroxy-acetophenonc hydrazonc. It occurs as a white, odorless. slightly bitter crystalline powder. It is slightly soluble... 

Formylation of amines and alcohols. Behai,8 discoverer of the reagent, found that it reacts unidirectionally with simple alcohols to produce alkyl formates free from acetates. Hurd et al. J found that acetic-formic anhydride (prepared from formic acid and ketene) reacts quantitatively with aniline to give formanilide. Another study10 established that acetic-formic anhydride mixes endothermally with 2-nitro-2-methyl-l-propanol, exothermally with 2-nitro-2-methyl-l,3-propanediol, and displays no appreciable temperature effect with either 2-nitro-l-butanol or tris-(hydroxymethyl)-nitromethane. Formic esters are favored by avoiding a high reaction temperature and by not using sulfuric acid as catalyst. The mixed anhydride has been used for the preparation of formyl fluoride.11... 

Hydroxylamine can be prepared from ammonia and hydrogen peroxide using a titanium silicalite catalyst in 83% yield.68 The by-product acetic acid could be recycled to acetic anhydride by pyrolyzing part of it to ketene. 

The Dp of prepolymers was affected by the nature of the monomer, the ratio between the monomer and acetic anhydride, and the reaction time. Short oligomers of 1-2 monomer units were prepared from the reaction of the diacid monomer with acetyl chloride in chlorinated hydrocarbon solution in the presence of an acid acceptor. Prepolymers were also prepared using propionic anhydride and butyric anhydride. However, these reagents boil at a higher temperature than acetic anhydride thus requiring vigorous conditions to remove the unreacted anhydride and acids by vacuum evaporation. Acetic acid mixed anhydride prepolymers were prepared also from the reaction of the diacid monomers with ketene [30],... 

The disubstituted malonic anhydrides can be prepared from the corresponding malonic acids and acetic anhydride in the presence of a little sulfuric acid, with neutralization of the mineral acid by treatment with barium carbonate and removal of acetic acid and acetic anhydride by distillation. The r dual malonic anhydride is decomposed by heating under low pressure. This method appears to have been used only for dimethylketene (80% yield), diethylketene (55% yield), methylethyl-ketene (65% yield), and dipropyl- and diisopropyl-ketenes (50% yields). 

Trifluoromethylated pyrones can also be prepared from acyl chlorides by reaction with pyridine and trifluoroacetic anhydride followed by capture of the intermediate trifluoroacyl ketene 8 with suitable reagents. Thus, addition of A -cyclohexenyl-morpholine to the intermediate from palmitoyl chloride gave pyrone 9 as the major product, accompanied by amide 10. Ethyl vinyl ether yielded pyrones 11a and 11b (through p-elimination of ethanol) [9] (Scheme 5). 

First prepared by C. F. Gerhardt from ben2oyl chloride and carefully dried potassium acetate (1), acetic anhydride is a symmetrical iatermolecular anhydride of acetic acid the iatramolecular anhydride is ketene [463-51-4]. Benzoic acetic anhydride [2819-08-1] undergoes exchange upon distillation to yield benzoic anhydride [93-97-0] and acetic anhydride. 

Acylation. Reaction conditions employed to acylate an aminophenol (using acetic anhydride in alkaU or pyridine, acetyl chloride and pyridine in toluene, or ketene in ethanol) usually lead to involvement of the amino function. If an excess of reagent is used, however, especially with 2-aminophenol, 0,A/-diacylated products are formed. Aminophenol carboxylates (0-acylated aminophenols) normally are prepared by the reduction of the corresponding nitrophenyl carboxylates, which is of particular importance with the 4-aminophenol derivatives. A migration of the acyl group from the O to the N position is known to occur for some 2- and 4-aminophenol acylated products. Whereas ethyl 4-aminophenyl carbonate is relatively stable in dilute acid, the 2-derivative has been shown to rearrange slowly to give ethyl 2-hydroxyphenyl carbamate [35580-89-3] (26). 

Acetic formic anhydride has been prepared by the reaction of formic acid with acetic anhydride2 3 and ketene,4,5 and of acetyl chloride with sodium formate.6 The present procedure is essentially that of Muramatsu.6 It is simpler than others previously described and gives better yields. It is easily adapted to the preparation of large quantities, usually with an increase in yield. Acetic formic anhydride is a useful intermediate for the formyl-ation of amines,3,7 amino acids,8,9 and alcohols,2,10 for the synthesis of aldehydes from Grignard reagents,11 and for the preparation of formyl fluoride.12... 

For acyl halides or anhydrides which do not afford ketenes in the presence of base (such as perfiuoroacyi halides), however, the a-acylmethylenephosphoranes can be prepared directly in one step from the phosphonium salts by using two equivalents of base by the present procedure (Table I).2 Both tetrahydrofuran and methylene chloride have been used as solvents and in the case of the title compound, tetrahydrofuran provides the best results. Good yields of the phosphoranes are generally obtained when is an electron-withdrawing group such as ester or nitrile. The yields of phosphoranes obtained for the thiomethyl or phenyl cases can be... 

Keteniminium salts arc an attractive alternative to ketenes for cycloaddition with alkenes to give cyclobutanones31-32. Keteniminium salts do not dimerize and are more electrophilic than ketenes. They can be easily prepared by treatment of a dialkyl amide with 2,4,6-trimethylpyri-dine (collidine) and triflic anhydride in an inert solvent or from an a-haloenamine and a Lewis acid. The cycloadditions of keteniminium salts with alkenes are stepwise, not concerted, so that products from syn addition to the alkene are not always obtained stereoselectively. Of greater concern is the fact that the major product from alkenes which can form a tertiary carbocation is the Kriedel-Crafts product. The cycloaddition procedure is therefore limited to mono- and 1,2-disubstituted alkenes. 

Enol acetates are obtained in moderate yield by means of acetic anhydride containing /7-toluenesulfonic acid703 or, better, bypassing ketene into the appropriate ketone containing 0.5 % of sulfoacetic acid at 60-80°.704 705 They are elegantly prepared by transesterification with isopropenyl acetate, CH2==CCH3(OCOCH3),706 which is obtained from acetone and ketene at 55°.704... 

Other carboxylic acids give mixed anhydrides in this reaction,180-182 but these readily disproportionate to the pair of symmetrical anhydrides. This provides a method of obtaining good yields of acid anhydrides that are difficultly accessible by other routes. In Org. Syn. Williams and Krynitzky183 describe the preparation of hexanoic anhydride from the acid and ketene. 

Acetic acid is the main impurity in acetic anhydride, which is prepared industrially from acetaldehyde or from acetic acid and ketene. The acid can be removed by fractionation, and residual amounts thereof by prolonged boiling with magnesium turnings.33... 

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