Keto hydrogenation

The color yield of acacetin is low in spite of a 4 -methoxyl group, and this is attributed to suppression of the A-ring activity owing to 5-hydroxyl to 4-keto hydrogen bonding, carbonyl attraction of electrons, and perhaps low solubility. 

Condensation of sulfone-derived anions with ketones - including enolizable ketones - can also be brought to fruition. It must be noted, however, that in reaction 3.10 [25], some 15% of starting material 38 is recovered, probably originating from competitive deprotonation of the highly acidic a-keto hydrogen. Good 1,2-diastereocontrol is also exercised in this case. 

To 2 ml. of the ester, add 2--3 drops of a saturated freshly prepared solution of scdium bisulphite. On shaking, a gelatinous precipitate of the bisulphite addition product (D) of the keto form separates, and on standing for 5-10 minutes usually crystallises out. This is a normal reaction of a ketone (see p. 344) hydrogen cyanide adds on similarly to give a cyanhydrin. 

The formation of ethyl acetoacetate is an example of a general reaction knowu as the acetoacetlc ester condensation in which an ester having hydrogen on the a-carbon atom condenses with a second molecule of the same ester or with another ester (which may or may not have hydrogen on the a-carbon atom) in the presence of a basic catalyst (sodium, sodium ethoxide, sodamide, sodium triphenylmethide) to form a p-keto-ester. The mechanism of the reaction may be illustrated by the condensation of ethyl acetate with another molecule of ethyl acetate by means of sodium ethoxide. ... 

The bromine adds on at the ethylenic linkage to form thedibromo compound (I), which easily loses hydrogen bromide to give the mono-bromo keto ester (II) ... 

The catalyst is inactive for the hydrogenation of the (isolated) benzene nucleus and so may bo used for the hydrogenation of aromatic compounds containing aldehyde, keto, carbalkoxy or amide groups to the corresponding alcohols, amines, etc., e.g., ethyl benzoate to benzyl alcohol methyl p-toluate to p-methylbenzyl alcohol ethyl cinnamate to 3 phenyl 1-propanol. 

Tertiary amines capable of eliminating a secondary amine to form a conjugated system can react with hydrogen cyanide to form y-keto nitriles by amine replacement. Thus (I) yields p-benzoylpropionitrile (IV) ... 

Asymmetric hydrogenation has been achieved with dissolved Wilkinson type catalysts (A. J. Birch, 1976 D. Valentine, Jr., 1978 H.B. Kagan, 1978). The (R)- and (S)-[l,l -binaph-thalene]-2,2 -diylblsCdiphenylphosphine] (= binap ) complexes of ruthenium (A. Miyashita, 1980) and rhodium (A. Miyashita, 1984 R. Noyori, 1987) have been prepared as pure atrop-isomers and used for the stereoselective Noyori hydrogenation of a-(acylamino) acrylic acids and, more significantly, -keto carboxylic esters. In the latter reaction enantiomeric excesses of more than 99% are often achieved (see also M. Nakatsuka, 1990, p. 5586). 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

The carbopalladation is extended to homoallylic amines and sulfides[466. Treatment of 4-dimethylamino-l-butene (518) with diethyl malonate and Li2PdCl4 in THF at room temperature leads to the oily carbopalladated complex 519, hydrogenation of which affords diethyl 4-(dimethylamino) butylmalonate (520) in an overall yield of 91%. Similarly, isopropyl 3-butenyl sulfide (521) is carbopalladated with methyl cyclopentanonecarboxylate and Li2PdCl4. Reduction of the complex affords the alkylated keto ester 522 in 96% yield. Thus functionalization of alkenes is possible by this method. 

The aryl- and heteroarylfluorosilanes 541 can be used for the preparation of the unsymmetrical ketones 542[400], Carbonylation of aryl triflate with the siloxycyclopropane 543 affords the 7-keto ester 545. In this reaction, transme-tallation of the siloxycyclopropane 543 with acylpalladium and ring opening generate Pd homoenolate as an intermediate 544 without undergoing elimination of/3-hydrogen[401],... 

Active methylene or methine compounds, to which two EWGs such as carbonyl, alko.xycarbonyl, formyl, cyano, nitro, and sulfonyl groups are attached, react with butadiene smoothly and their acidic hydrogens are displaced with the 2,7-octadienyl group to give mono- and disubstituted compounds[59]. 3-Substituted 1,7-octadienes are obtained as minor products. The reaction is earned out with a /3-keto ester, /9-diketone, malonate, Q-formyl ketones, a-cyano and Q-nitro esters, cya noacetamide, and phenylsulfonylacetate. Di(octadienyl)malonate (61) obtained by this reaction is converted into an... 

A hydrogen attached to the a carbon atom of a p keto ester is relatively acidic Typical p keto esters have pA values of about 11 Because the a carbon atom is flanked by two electron withdrawing carbonyl groups a carbanion formed at this site is highly stabi hzed The electron delocalization m the anion of a p keto ester is represented by the res onance structures... 

Claisen condensations involve two distinct experimental operations The first stage concludes m step 4 of Figure 21 1 where the base removes a proton from C 2 of the p keto ester Because this hydrogen is relatively acidic the position of equilibrium for step 4 lies far to the right... 

Hydrogen bonding to a carbonyl group causes a shift to lower frequency of 40 to 60 cm k Acids, amides, enolized /3-keto carbonyl systems, and o-hydroxyphenol and o-aminophenyl carbonyl compounds show this effect. All carbonyl compounds tend to give slightly lower values for the carbonyl stretching frequency in the solid state compared with the value for dilute solutions. 

Methyl Isoamyl Ketone. Methyl isoamyl ketone [110-12-3] (5-methyl-2-hexanone) is a colorless Hquid with a mild odor. It is produced by the condensation of acetone and isobutyraldehyde (164) in three steps which proceed via the keto-alcohol dehydration to 5-methyl-3-hexen-2-one, and hydrogenation to 5-methyl-2-hexanone. 

Since polar solvents would be expected to stabilize polar forms, a retreat towards the hydroxy tautomer (71) would be predicted in solvents less polar than water, and in the vapour phase. This is borne out in practice at equilibrium both 2- and 4-hydroxypyridine (as well as the 3-hydroxy compound, which even in water exists as an approximate 1 1 mixture of OH and NH forms) exist as such, rather than as the pyridinones. However, the 2- and 4-quinolinones remain in the NH (keto) forms, even in the vapour phase. Hydrocarbon or other solvents of very low polarity would be expected to give results similar to those in the vapour phase, but intermolecular association by hydrogen bonding often leads to a considerably greater proportion of polar tautomers being present than would otherwise have been predicted (77ACR186, 78JOC177). 

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