Hydrates from water + ketones

In contrast, the acid-catalyzed hydration of arylbenzoylacetylenes differs markedly from the hydration of a-unsaturated ketones. Hydration of unsaturated ketones has been shown to proceed via a 1,4-addition mechanism where protonation occurs on oxygen to give an oxonium salt, followed by attack of water at the 0-carbon to give a hydroxy enol. The rate-limiting step has been shown to be the protonation of the hydroxy enol (27) ... 

The aldehyde/ketone 1 (4.00 mmol), or the ketone 7 (2.00 mmol), or the isothio-cyanate 5 (2.00 mmol) was ball-milled with the solid hydrazine-hydroquinone complex 2 (2.00 mmol) at 25-30 °C for lh (3 h in the case of Id). The yield was quantitative in all cases, as spectroscopically pure mixtures of 3, 6, 8 with 4 were obtained. Hydroquinone 4 was removed by 5 min trituration with 20 mL of water, filtration and three washings with 2 mL of water, each. The residue was dried in a vacuum to obtain the pure products. 4 was recycled from the aqueous washings by evaporation, addition of 1.0 g of 80% hydrazine hydrate in water per 4 mmol of initially reacted 2 and recrystallization to give 520 mg (91%) of pure 2 after filtration, washing with water and drying. 

With regard to carboxylic derivatives, there is generally little difference in chemical shift among the various trifluoroacetic acid derivatives, as exemplified by the examples in Scheme 5.30. Also, the effect of moving the CF3 farther from the carboxylic acid function is similar to that seen with the aldehydes and ketones. Trifluoromethyl ketones will often be in equilibrium with their hydrated form, in which case signals from both the hydrate and water-free ketone will be observed, as is the case for the following pyruvate example. 

Acidic work-up of 18 furnishes ketone 22. Further addition of HC1 and acetic acid at 70 °C results in cleavage of the pivaloyl anilide to yield the unprotected orf/io-ketoaniline as hydrochloride hydrate 5, since ketones with neighboring electron-withdrawing groups undergo nucleophilic addition of water. 5 directly crystallized from the reaction mixture and was obtained in 87 % yield with a purity of > 98 %. These three steps were carried out on a 3,700 g scale. 

Since hydrochloride hydrate 5 crystallized from the reaction mixture, an additional step was necessary to obtain the desired ortho-ketoaniline 6. The free base was obtained by treatment of 5 with NaOAc in a pH range of 4.0-6.0, which had to be carefully adjusted during the reaction. Hydrate formation of ketones is a reversible process in solution, and the equilibrium fraction of o-aminoketonc 6 was continuously extracted from the aqueous layer until removal of hydrating water was complete. The extraction was carried out on a 3,000 g scale. 

Organolithium reagents can be used to synthesize ketones from carboxylic acids. Organolithiums are so reactive toward carbonyls that they attack the lithium salts of carboxylate anions to give dianions. Protonation of the dianion forms the hydrate of a ketone, which quickly loses water to give the ketone (see Section 18-13). 

Loss of water from the hydrate of the ester occurs by the same mechanism as loss of water from the hydrate of a ketone (Section 18-13). Protonation of either of the hydroxyl groups allows it to leave as water, forming a resonance-stabilized cation. Loss of a proton from the second hydroxyl group gives the ester. 

A study [98] of proton transfer from acetylacetone, trifluoroacetyl-acetone and hexafluoroacetylacetone has shown that rates of proton transfer to water decrease along the series, whereas the measured acidity increases. This corresponds to a negative value for 3S which is different from the result j3B = 0.48 measured [85] for proton transfer between acetylacetone and carboxylate ions. The opposite order for rates and acidities was attributed to a change in hydration of the ketones along the series neither rates nor equilibrium data could be corrected to take account of this factor. 

Hydrates cannot be isolated from the ketones and aldehydes seen most often in this book, but in a few special cases a hydrate is isolated. If the carbon attached to the carbonyl carbon (the a-carbon) has strong electron-withdrawing groups on it—and, particularly, if no hydrogens are on the a-carbon adjacent to the carbon bearing the two OH units—the hydrate may be isolated. Chloral (40) is a common name for trichloroethanal (trichloroacetaldehyde is also used as a common name) and it reacts with water to form a stable hydrate, 41. 

Loss of water from the hydrate forms a ketone that reacts with the amino acid to form an imine. 

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. 

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... 

Reactions in chloroaluminate(III) salts and other related binary salts often proceed smoothly to give products. However, it should be noted that these salts are water-sensitive and must be handled under dry conditions. They react with water to give hydrated aluminium(III) ionic species and HCl. When a reactant or product contains a heteroatomic functional group, such as a ketone, a strong ketone/alumini-um(III) chloride adduct is formed. In these cases, this adduct can be difficult to separate from the ionic liquid at the end of a reaction. The isolation of the product often... 

Pt-catalyzed hydration of various aliphatic and aromatic alkynes under phase transfer conditions in (CH2C1)2/H20 in the presence of Aliquat 336 led to either a Markovnikov product, mixtures of two ketones, or ketones with the carbonyl group positioned away from the bulky side.72 In the absence of the phase transfer reagent, Aliquat 336, hardly any reaction took place. Recently, a hydrophobic, low-loading and alkylated polystyrene-supported sulfonic acid (LL-ALPS-SO3H) has also been developed for the hydration of terminal alkynes in pure water, leading to ketones as the product.73 Under microwave irradiation, the hydration of terminal arylalkynes was reported to proceed in superheated water (200°C) without any catalysts.74... 

The monoketone bis(2,2, /V,/V -bipyridyl)ketone forms a [CoinL2]+ complex on reaction with [Co(NH3)4(C03)]+ in water.981 As reported for a quite different Co11 complex, the ketone is hydrated to form the gem diol which binds as a monodeprotonated O-donor along with the two pyridine groups in a tridentate chelate, with very little distortion from octahedral observed in the complex. This appears to represent a facile route for this type of inherently poor donor to achieve coordination. Chelated /3-diketonate anions are long-studied examples of O-donor chelates, and continue to be examined. A simple example is the m-[Co(acac)2(NH 3)2]1 (acac = 2,4-pentane-dionate), structurally characterized and utilized to produce molecular mechanics force field parameters for /3-diketones bound to Co111.982... 

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