1.1- Diols ketone hydrates

Ketones and aldehydes, because they are unsaturated, readily add water to give a 1,1-diol or hydrate ... 

Aldehydes and ketones react with water to yield 1,1-diols, or geminal (gem) diols. The hydration reaction is reversible, and a gem diol can eliminate water to regenerate an aldehyde or ketone. 

Peroxynitrite (ONOO ) is generated intracellularly from NO and superoxide anion. Ketones have been found to catalyse its decomposition via dioxirane intermediates. Decomposition of Caro s acid (peroxymonosulfuric acid, H2SO5) is similarly catalysed. Kinetics of the decomposition catalysed by acetones with strongly electron-withdrawing substituents (e.g. fluoro, 1,1,1-trifluoro and hexafiuoro) show evidence of the involvement of the ketone hydrate (i.e. the 1,1-diol) and its anion. ... 

Aldehydes and ketones react with water to form gem diols cahed hydrates. The equihbrium constant for hydrate formation depends on both steric and electronic factors. As in the case of cyanohydrins, the reaction with aldehydes is far more favorable than the reaction with ketones. 

The pinacol hydrate may be used (i) for conversion to pina-colone (see below), and (ii) to illustrate the oxidation of 1,2-diols to aldehydes or ketones by periodic acid (p. 145),... 

Terminal alkyne anions are popular reagents for the acyl anion synthons (RCHjCO"). If this nucleophile is added to aldehydes or ketones, the triple bond remains. This can be con verted to an alkynemercury(II) complex with mercuric salts and is hydrated with water or acids to form ketones (M.M.T. Khan, 1974). The more substituted carbon atom of the al-kynes is converted preferentially into a carbonyl group. Highly substituted a-hydroxyketones are available by this method (J.A. Katzenellenbogen, 1973). Acetylene itself can react with two molecules of an aldehyde or a ketone (V. jager, 1977). Hydration then leads to 1,4-dihydroxy-2-butanones. The 1,4-diols tend to condense to tetrahydrofuran derivatives in the presence of acids. 

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). 

Aldehyde or ketone Water Gemmal diol (hydrate) ... 

Geminal diol (Section 17 6) The hydrate R2C(OH)2 of an aldehyde or a ketone... 

With water, these ketones form stable monohydrates or higher nonstoichio-metric hydrates [2, 6, 7, 8, 9, 1Q, dehydration of the gemmal diols is achieved by treatment with hot concentrated sulfuric acid or phosphorus pentoxide [4]... 

The acid-catalvzed hydration reaction begins with protonation of the carbonyl oxygen atom, which places a positive charge on oxygen and makes the carbonyl group more electrophilic. Subsequent nucleophilic addition of water to the protonated aldehyde ot ketone then yields a protonated gem diol, which loses H+ to give the neutral product (Figure 19.5). 

Now the ether may be disconnected, diol (13) being the obvious starting material. This contains an i-hydroxy ketone so we might consider disconnecting an acyl anion equivalent from a ketone. If we use an acetylene, the starting material (14) is symmetrical so hydration presents no problems,... 

Monoketones are poor ligands. Di-2-pyridylketone ((py)2C O) accommodates this deficiency in an unusual way when it reacts with Co(OAc)2 to form clusters, including [Co4(HQ)4(0 Ac)4] II20, where the monodeprotonated hydrated gem-diol form of the ketone (HQ-) (Equation (5)) binds as an ionic ligand.423 This cluster adopts a tetranuclear cubane shape with four deprotonated O atoms of the diol occupying the alternating vertices to the Co ions. 

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... 

These observations emphasize the fact that gem-diols are usually unstable and decompose to carbonyl compounds. However, it can be demonstrated that hydrate formation does occur by exchange labelling of simple aldehyde or ketone substrates with 0-labelled water. Thus, after equilibrating acetone with labelled water, isotopic oxygen can be detected in the ketone s carbonyl group. 

Replacement of the hydroxamic acid moiety of SAHA by an alternative chelator has been the subject of several studies. Suzuki and Miyata et al. have shown that replacement of the hydroxamic acid of SAHA with a free thiol moiety does not affect the enzymatic HDAC inhibition capability of the compound [57]. Furthermore, replacement of the hydroxamic acid of SAHA by a trifluoromethyl ketone was investigated by Frey et al. (Fig. 8) [58]. The activated ketone is readily hydrated to form the vicinal diol, a structural feature known to bind to zinc-dependent proteases [59]. The in vitro evaluation was done on a partially purified HDAC preparation consisting largely of HDAC 1 and HDAC2 [60], exhibiting an IC50 of 6.7 xM. 

Aldehyde and ketone reacts with water in the presence of aqueous acid or base to form hydrate. A hydrate is a molecule with two hydroxyl groups on the same carbon. It is also called gem-diol. Hydration proceeds through the two classic nucleophilic addition mechanisms with water in acid... 

Several preparative methods exist for the synthesis of 3(2//)-dihydrofuranones. 2,5-Disubstituted or 2,2,5,5-tetrasubstituted 3(2i/)-dihydrofuranones are usually prepared by reaction of sodium or lithium acetylide with a ketone to yield an alkynic alcohol which is then treated with a carbonyl compound in the presence of base to afford alkynic diols. Mercury catalyzed hydration of the resultant diols in the presence of acid affords the furanones in good yields (76JMC709). 

It is beneficial in terms of yield to convert an a,/3-unsaturated ketone into the cyclopropyl ketone using dimethyloxosulfonium methylide. The epoxide, formed as above, is rearranged during chromatography on silica gel. The corresponding pent-2-ene-l,5-diols are also formed, presumably through hydration of the cation, and these may be dehydrated to the pyran with p-toluenesulfonic acid (74JCS(P1)1674). 

Hydration of Massively substituted epoxides in acid can be expected to yield significant amounts of elimination and/or rearrangement products derivable from an intermediate c rbonium ion This expectation is amply fulfilled with 2,3- poxy-2r4J4-trim thylpentane (Eq. 610), which yields in addition to the desired 1,2-diol, an unsaturated alcohol, a ketone, and several other products.61 ... 

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