Hydrate from ketones

We showed in Figs. 3-2 and 3-3 that the tetrahedral intermediate which is initially formed from the reaction of a nucleophile with a carbonyl compound may further react in a number of different ways. In this section, we will consider some reactions which proceed along the pathway indicated in Fig. 3-3. The hydration of ketones is a reaction analogous to the hydrolysis of an ester, with the first step of the reaction involving nucleophilic attack of water on the carbonyl group. The tetrahedral intermediate is trapped by reaction with a proton to yield the hydrated form of the ketone, the geminal diol (Fig. 3-15). Similar reactions occur with alcohols as nucleophiles to yield, initially, hemiacetals. 

This is ordinary electrophilic addition, with rate-determining protonation as the first step. Certain other alkynes have also been hydrated to ketones with strong acids in the absence of mercuric salts. Simple alkynes can also be converted to ketones by heating with formic acid, without a catalyst.Lactones have been prepared from trimethylsilyl alkenes containing an hydroxyl unit elsewhere in the molecule, when reacted with molecular oxygen, CuCla, and a palladium catalyst. ... 

In acidic media, polarized multiple bonds often undergo acid catalyzed addition, and a common mode of addition is the Ad 2. Deprotonation of the nucleophile by solvent gives the neutral compound. Common examples of this easily reversible Adg2 reaction are the formation of hydrates (NuH is H2O) and, if NuH is ROH, hemiacetals (from aldehydes) and hemiketals (from ketones). Usually this reaction favors reactants. 

Place 80 g, of hydroxylamine sulphate (or 68-5 g. of the hydrochloride), 25 g. of hydrated sodium acetate, and 100 ml. of water in a 500 ml. flask fitted with a stirrer and a reflux water-condenser, and heat the stirred solution to 55-60°. Run in 35 g (42 nil,) of -hexyl methyl ketone, and continue the heating and vigorous stirring for ij hours. (The mixture can conveniently be set aside overnight after this stage.) Extract the oily oxime from the cold mixture twice with ether. Wash the united ethereal extract once with a small quantity of water, and dry it with sodium sulphate. Then distil off the ether from the filtered extract, preferably using a distillation flask of type shown in Fig. 41 (p. 65) and of ca, 50 ml, capacity, the extract being run in as fast as the ether distils, and then fractionally distil the oxime at water-pump pressure. Collect the liquid ketoxime, b.p. 110-111713 mm. Yield, 30-32 g. 

Pinacol upon dehydration with acid catalysts e.g., by distillation from 6A sulphuric acid or upon refluxing for 3—4 hours with 50 per cent, phosphoric acid or hydrated oxalic acid) is transformed into methyl ter<.-butyr ketone or plnacolone ... 

The addition of acetylides to oxiranes yields 3-alkyn-l-ols (F. Sondheimer, 1950 M.A. Adams, 1979 R.M. Carlson, 1974, 1975 K. Mori, 1976). The acetylene dianion and two a -synthons can also be used. 1,4-Diols with a carbon triple bond in between are formed from two carbonyl compounds (V. Jager, 1977, see p. 52). The triple bond can be either converted to a CIS- or frans-configurated double bond (M.A. Adams, 1979) or be hydrated to give a ketone (see pp. 52, 57, 131). 

Methyl Isopropyl Ketone. Methyl isopropyl ketone [563-80-4] (3-methyl-2-butanone) is a colorless Hquid with a characteristic odor of lower ketones. It can be produced by hydrating isoprene over an acidic catalyst at 200—300°C (150,151) or by acid-catalyzed condensation of methyl ethyl ketone and formaldehyde to 2-methyl-l-buten-3-one, foUowed by hydrogenation to the product (152). Other patented preparations are known (155,156). Methyl isopropyl ketone is used as an intermediate in the production of pharmaceuticals and fragrances (see Perfumes), and as a solvent (157). It is domestically available from Eastman (Longview, Texas) (47). 

Oxo Ion Salts. Salts of 0x0 ions, eg, nitrate, sulfate, perchlorate, hydroxide, iodate, phosphate, and oxalate, are readily obtained from aqueous solution. Thorium nitrate is readily formed by dissolution of thorium hydroxide in nitric acid from which, depending on the pH of solution, crystalline Th(N02)4 5H20 [33088-17 ] or Th(N02)4 4H20 [33088-16-3] can be obtained (23). Thorium nitrate is very soluble in water and in a host of oxygen-containing organic solvents, including alcohols, ethers, esters, and ketones. Hydrated thorium sulfate, Th(S0 2 H20, where n = 9, 8, 6, or 4, is... 

Methyl ketones are important intermediates for the synthesis of methyl alkyl carbinols, annulation reagents, and cyclic compounds. A common synthetic method for the preparation of methyl ketones is the alkylation of acetone derivatives, but the method suffers limitations such as low yields and lack of regioselectivity. Preparation of methyl ketones from olefins and acetylenes using mercury compounds is a better method. For example, hydration of terminal acetylenes using HgSO gives methyl ketones cleanly. Oxymercuration of 1-olefins and subsequent oxidation with chromic oxide is... 

A solution of the 3-ketone hydrate (0.15 g) in acetone- -heptane is heated to boiling. After the acetone has been boiled off, a trace of concentrated hydrochloric acid is added to the -heptane solution and boiled for an additional 2 min. After cooling, the resulting crystals are collected by filtration, washed with dry -heptane and dried in vacuo overnight. Recrystallization from dry -heptane gives 17 -hydroxy-4,4-difluoroestr-5-en-3-one 0.98 g mp 123.5-124.5° [a] 134° (CHCI3). 

The salts of some enamines crystallize as hydrates. In such cases it is possible that they are derived from either the tautomeric carbinolamine or the amino ketone forms. Amino ketone salts (93) ( = 5, 11) can serve as examples. The proton resonance spectra of 93 show that these salts exist in the open-chain forms in trifluoroacetic acid solution, rather than in the ring-closed forms (94, n = 5, 11). The spectrum of the 6-methylamino-l-phenylhexanone cation shows a multiplet at about 2.15 ppm for phenyl, a triplet for the N-methyl centered at 7.0 ppm and overlapped by signals for the methylene protons at about 8.2 ppm. The spectrum of 93 ( = 11) was similar. These assignments were confirmed by determination of the spectrum in deuterium oxide. Here the N-methyl group of 93 showed a sharp singlet at about 7.4 ppm since the splitting in —NDjMe was much reduced from that of the undeuterated compound. 

While the usual eonsequence of hydration of enamines is eleavage to a secondary amine and an aldehyde or ketone, numerous cases of stable carbinolamines are known (102), particularly in examples derived from cyclic enamines. The selective terminal hydration (505) of a cross-conjugated dienamine-vinylogous amide is an interesting example which gives an indication of the increased stabilization of the vinylogous amide as compared to simple enamines, which is also seen in the decreased nucleophilicity of the conjugated amino olefin-carbonyl system. 

Extension of the hydration reaction to hydrogen peroxide has shown that stable peroxides are formed from enamines and the imonium salts derived from secondary amines and ketones (506,507). 

Besides acetophenone, this reaction was also applied to p-chloro- andp-methoxyacetophenone, and even to an aliphatic ketone, acetone (although the yield was stated to be only half as large as that obtained from mesityl oxide, i.e., less than 30%, Dorofeenko and co-workers reported a 45% yield of 2,4,6-trimethylpyrylium perchlorate from acetone, acetic anhydride, and perchloric acid), and is the standard method for preparing pyrylium salts with identical substituents in positions 2 and 4. The acylating agent may be an anhydride in the presence of anhydrous or hydrated ferric chloride, or of boron fluoride, or the acid chloride with ferric chloride.Schneider and co-workers ... 

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