Chloral ketones

Monohydric alcohols, aldehydes (including chloral hydrate), ketones, cinnamic acid, amines (2-naphthylaminc is odourless), nitrophenols (resemble both phenol and nitro-compound),... 

The [ 2 + 4]-cycloaddition reaction of aldehydes and ketones with 1,3-dienes is a well-established synthetic procedure for the preparation of dihydropyrans which are attractive substrates for the synthesis of carbohydrates and other natural products [2]. Carbonyl compounds are usually of limited reactivity in cycloaddition reactions with dienes, because only electron-deficient carbonyl groups, as in glyoxy-lates, chloral, ketomalonate, 1,2,3-triketones, and related compounds, react with dienes which have electron-donating groups. The use of Lewis acids as catalysts for cycloaddition reactions of carbonyl compounds has, however, led to a new era for this class of reactions in synthetic organic chemistry. In particular, the application of chiral Lewis acid catalysts has provided new opportunities for enantioselec-tive cycloadditions of carbonyl compounds. 

A closely related reaction has been performed with other aldehydes and even with ketones without a catalyst, but with heat. The aldehydes and ketones here are active ones, such as chloral and acetoacetic ester. The product in these cases is a 3-hydroxy alkene, and the mechanism is pericyclic ... 

The acetoacetyl group may be supplied as ketene dimer (p T277), leaving alcohol (31). You may have considered chlorinating ketone (32) or adding CCl to aldehyde (33) to make (31) but you probably did not see the disconnection to chloral and isobutylene (3lb),... 

The cycloaddition of aldehydes and ketones with ketene under the influence of quinine or quinidine produce chiral 2-oxetanones [46,47]. Solvolytic cleavage of the oxetanone, derived from chloral, and further solvolysis of the trichloromethyl group leads to (5)- and (R)-malic acids with a 98% ee [46] (the chirality of the product depends on the configuration of the catalyst at C-8 and, unlike other alkaloid-induced reactions, it is apparently independent of the presence of the hydroxyl group). No attempts have been made to catalyse the reaction with chiral ammonium salts. 

The possibility of hydrogenating halogenated aldehydes and ketones by means of phytochemical reduction was tested as early as 1913 the successful results in this field clearly demonstrate the importance of this method. Lintner and Ltters found that chloral hydrate can be converted to trichloroethyl alcohol. This transformation takes place so easily that, according to Willstatter and Duisberg, it can be used under favorable experimental conditions as a convenient method for the preparation of the halogenated alcohol. The tribromoethyl alcohol may be prepared in an analogous manner. 

Aldehydes, ketones, and quinones react with ketenes to give p-lactones, diphenylketene being used most often. The reaction is catalyzed by Lewis acids, and without them most ketenes do not give adducts because the adducts decompose at the high temperatures necessary when no catalyst is used. When ketene was added to chloral Cl3CCHO in the presence of the chiral catalyst (+ )-quinidine, one enantiomer of the p-lactone was produced in 98% enantiomeric excess.777 Other di- and trihalo aldehydes and ketones also give the reaction enantioselectively, with somewhat lower ee values.778 Ketene adds to another molecule of itself ... 

The order of reactivities of various functional groups determined under standard conditions (using externally generated diborane, and tetrahydrofuran as solvent) is acid > alkene > ketone > nitrile > epoxide > ester > acid chloride.33 Acids, aldehydes, ketones, epoxides, nitriles, lactones and azo compounds are reduced rapidly, esters more slowly and chloral, acid chlorides and nitro compounds are inert. Double bonds undergo the hydroboration reaction,25 nitriles and azo compounds are reduced to amines, and the remaining groups to alcohols. Ketones can be reduced selectively in the presence of epoxides. Contrary to the order of reactivities given above, it has been claimed that nitriles are reduced more rapidly than ketones.223... 

Keskin, H. Synthesis of chloral-methyl-ketones and keto-fatty-acids. Rev. Fac. Sci. Univ. Istanbul A 15, 1 (1950) Chem. Abstr. 45, 2904 (1951). 

With acid catalysis, alcohols add to the carbonyl group of aldehydes to give hemiacetals [RCH(OH)OR ]. Further reaction with excess alcohol gives acetals [RCH(OR )2]- Ketones react similarly. These reactions are reversible that is, acetals can be readily hydrolyzed by aqueous acid to their alcohol and carbonyl components. Water adds similarly to the carbonyl group of certain aldehydes (for example, formaldehyde and chloral) to give hydrates. Hydrogen cyanide adds to carbonyl compounds as a carbon nucleophile to give cyanohydrins [R2C(OH)CN],... 

In the case of the 9-catalyzed aldol reactions of ketones and aldehyde donors that have a high affinity for water (e.g., chloral, trifluoroacetaldehyde, aqueous formaldehyde or the corresponding hydrates of the aldehydes), the addition of 100-500 mol% water to the reaction mixture accelerated the reaction rate and afforded the products with higher enantiomeric excess (Scheme 2.13) [16]. The presence of a catalytic amount of water (20 or 50 mol%) or no addition of water... 

Scheme 2.13 Aldol reaction of a ketone and chloral catalyzed by 9 [16].

In the Oppenauer oxidation, an activated carbonyl compound acts as a hydride acceptor in the selective oxidation of an alcohol to give a ketone. Krohn et al. (208) used SiCL-anchored Zr(OnPr)4 in combination with chloral ... 

These stability effects are apparent in the equilibrium constants for hydration of ketones and aldehydes. Ketones have values of Keq of about 10-4 to 10-2. For most aldehydes, the equilibrium constant for hydration is close to 1. Formaldehyde, with no alkyl groups bonded to the carbonyl carbon, has a hydration equilibrium constant of about 40. Strongly electron-withdrawing substituents on the alkyl group of a ketone or aldehyde also destabilize the carbonyl group and favor the hydrate. Chloral (trichloroacetaldehyde) has an electron-withdrawing trichloromethyl group that favors the hydrate. Chloral forms a stable, crystalline hydrate that became famous in the movies as knockout drops or a Mickey Finn. 

Material taken straight from the refrigerator should be warmed gently prior to examination for odour. If possible, the opinions of several colleagues should be obtained on any abnormal odour. Many poisons can be detected in this way, but the test is very subjective, and some people have a poor sense of smell (e.g. cyanide detection by odour is an inherited ability). In favourable circumstances it is a very sensitive test for instance, cyanide, chloroform, and toluene can be detected at about 1 ppm. from the usual characteristic odours of sulphides, aldehydes, ketones, and esters, etc., ftie analyst should be familiar with the smell of chloral hydrate, ethchlorvynol, methylpentynol, phenelzine. 

Aldehydes and ketones undergo reduction to primary and secondary alcohols (e.g. chloral is converted to trichloroethanol and prednisone is reduced to prednisolone). 

---