Ketones acylic

Acylation of ketones (Sec tion 21 4) Diethyl carbo nate and diethyl oxalate can be used to acylate ketone enolates to give p keto esters... 

The acylation of enamines derived from cyclic ketones, which can lead to the acyl ketone or ring expansion (692-694), was studied by NMR and mass spectroscopic analysis of the products (695,696). In a comparative study of the rates of diphenylketene addition to olefins, a pronounced activation was observed in enamines (697). Enamine N- and C-acylation products were obtained from reactions of Schiff s bases (698), vinylogous urethanes (699), cyanamides (699), amides (670,700), and 2-benzylidene-3-methylbenzothiazoline (672) with acid chlorides, anhydrides, and dithio-esters (699). 

A chemical reaction in which the carboxyl group of an a-amino acid is replaced by an acyl group Le., an acyl-decarboxylation). In this reaction, an a-amino acid is reacted with an anhydride in the presence of pyridine and the resulting product is an A-acylated ketone. In certain instances, A-substituted amino acids will also act as reactants. 

As expected, the para-acylated ketone 3 is the major reaction product, with only minor yields of the ortho-acylated product formed. Reaction is very rapid and complete conversions are obtained. Catalyst TOP numbers are >19000h under these conditions. Enolisation and further reaction with the anhydride results in formation of the vinyl ester. Minor amounts of diacile and side products are formed. Similar performances are observed with both supported and nonsupported ST A (at equivalent ST A loading in reactor). Use of nonsupported ST A resulted in agglomeration and deposition of the material onto the reactor wall, whereas the silica supported material could be readily removed by filtration. 

Enantioselective alkylation of acylic ketones is also possible,2 but in this case the enantioselectivity is dependent on the geometry of the chiral imine. Thus the product of thermodynamic alkylation (of the E-isomer) is the enantiomer of the... 

In situ generated acyllithium reagents not only can acylate ketones, but also can acylate aldehydes,3 esters,4 lactones,5 isocyanates and isothiocyanates,6 carbodiimides,7 carbon disulfide and carbonyl sulfide,8 organic disulfides,9 and trialkylchlorosilanes.10 For reviews, see references 11 and 12. This direct, nucleophilic acylation procedure, when applicable, makes unnecessary the usually... 

Oxalic esters (for electronic reasons) and formic esters (because of their low steric hindrance) are reactive esters that can acylate ketone enolates formed with NaOR in equilibrium reactions. Formic esters acylate ketones to provide formyl ketones (for example, see Figure 13.61). It should be noted that under the reaction conditions the conjugate base of the active-methylene formyl ketone is formed. The neutral formyl ketone is regenerated upon acidic workup. 

The enamine alkylation procedure is sometimes called the Stork reaction, after its inventor, Gilbert Stork of Columbia University. The Stork reaction can alkylate or acylate the a position of a ketone, using a variety of reactive alkyl and acyl halides. Some halides that react well with enamines to give alkylated and acylated ketone derivatives are the following ... 

Alkylation or acylation of a ketone or aldehyde using its enamine derivative as the nucleophile. Acidic hydrolysis regenerates the alkylated or acylated ketone or aldehyde, (p. 1053)... 

The same authors116 showed that 1,3-diketones 198 react easily with benzonitrile in the presence of a HC104-Ac20 mixture to form 3-azapyrylium perchlorates 199 (equation 63). This reaction did not occur without acetic anhydride, which is a catalyst since the acylium ions are not included in the end products. The application of the C-acylated ketones 198 leads to 3-azapyrylium salts 199 which are isomeric to those mentioned above (194), i.e. products 199 have an inverted orientation of heteroatoms comparatively to the three-carbon fragment of the cycle116. The azapyrylium salts 199 can be hydrolyzed to the enamides 200. 

As the imidazole nucleus does not undergo Friedel-Crafts acylation, ketone substituents must be introduced indirectly, either before the ring is formed34,41,210,275,435 or by modification of existing substituents.210 Roe210 prepared 2-acetylimidazole (92) by oxidation of l-(imidazol-2 -yl)ethanol (91) with chromic oxide in pyridine. The acyl-substituted imidazoles have distinctive infrared and ultraviolet... 

Friedel-Crafts Acylation (Ketone Formation) (RC0)20 + ArH RCOAr + RCOOH... 

One of the effective reagents for highly chemoselective dithioacetalization of carbonyl compounds is ceric ammonium nitrate (CAN) in chloroform. When a mixture of benzaldehyde and acetophenone was allowed to react with 1,2-ethanedithiol and a catalytic amount of CAN, the 1,3-dithiolane derived from the aldehyde was obtained in 84% yield while the ketone was recovered unchanged. It is noteworthy that aromatic ketones, 7-lactones, and acylic ketones did not react at all under these conditions and even at elevated temperatures for longer reaction times <1995T7823>. 

Carboxy includes carboxy (carboxylic acids), alkoxycarbonyl (esters), carbamoyl (amides), thiocarbamoyl, hydrazinocarbamoyl (hydrazides), guanidinocarbonyl, azidocarbonyl (azides), chlorocarbonyl (acid chlorides), amidino, C-hydrazino-C-iminomethyl, C-alkoxy-C-iminomethyl (imino ethers), C-alkylthio-C-iminomethyl (iminothioethers), cyano (nitriles), C-formyl(aldehydes), dialkoxymethyl (acetals of aldehydes), C-acyl (ketones), isocyanato, and thiocyanato groups. 

This alternative to the Friedel-Crafts reaction, extensively developed by Stille and coworkers, is particularly important, since the reaction conditions are essentially neutral, and so provides a method for acylation of compounds containing an acid-sensitive functionality which would preclude the use of the Friedel-Crafts reaction. Reaction temperatures are often below 100 C, and high (1000-fold) turnovers of the catalyst have been achieved. Solvents employed include chloroform, toluene, and, on occasions, HMPA. Some reactions have been carried out under an atmosphere of carbon monoxide to prevent excessive decarbonylation of the acyl palladium intermediate. Indeed, carbonylative coupling of alkenylstannanes with allyl halides in the presence of carbon monoxide ca. 3 atm or greater 1 atm =101 kPa) offers an alternative to the Friedel-Crafts acylation, ketones being formed by the reaction of the stannane with the acyl species formed by carbon monoxide insertion into the allyl palladium intermediate. ... 

One of the reactions used most extensively to acylate ketones employs formate esters to produce a-formyl or hydroxymethylene ketones. Earlier work has been reviewed this section summarizes the important reactions of these products, particularly in alicyclic chemistry. As an illustration, the conversion of 2-methylcyclohexanone (157) into its 6-hydroxymethylene derivative and the subsequent chemistry of that compound are shown in Scheme 63. Such ketones normally undergo formylation at the less... 

Several oxazole-4-aldehydes have been described, while only one oxazole-2-aldehyde is known so far 2 4 they are fairly stable to oxidation by air. Since the oxazoles are not known to undergo Friedel-Crafts acylation, ketone substituents are introduced indirectly into the nucleus, either before the ring is formed40 332 391 or by modification of substituents already present.147 4-Acetyloxazoles are oxidized to the corresponding acids with sodium hypobromite.147 Both oxazolyl aldehydes and ketones form derivatives with hydroxylamine, phenylhydrazine, etc., as expected. 

Likewise, 3-keto aldehydes, malonaldehyde, acetylene ketones and a-acyl ketone-X -acetals can be employed for the Guareschi synthesis [86]. 

In the manufacture of an acylated ketone, dimethylformamide was charged into a 2.2 m Pfaudler glass-lined reactor, blanketed with nitrogen. A quantity of sodium hydride dispersed in oil was added, together with diethyl-carbonate. When the mix recorded a temperature of 323 K, ketone and methylace-tylpyridine were added. In the incident, an exothermic reaction occurred before the addition of the ketone. The investigation revealed that the chemistry of the process had not been properly investigated and was not fully understood. 

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