Ketones hydrated forms

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... 

A mixture of both possible ketones results when an unsymmetrically substituted internal alkyne (RC=CR ) is hydrated. The reaction is therefore most useful when applied to a terminal alkyne (RC=CH) because only a methyl ketone is formed. 

The hydration of triple bonds is generally carried out with mercuric ion salts (often the sulfate or acetate) as catalysts. Mercuric oxide in the presence of an acid is also a common reagent. Since the addition follows Markovnikov s rule, only acetylene gives an aldehyde. All other triple-bond compounds give ketones (for a method of reversing the orientation for terminal alkynes, see 15-16). With allqmes of the form RC=CH methyl ketones are formed almost exclusively, but with RC=CR both possible products are usually obtained. The reaction can be conveniently carried out with a catalyst prepared by impregnating mercuric oxide onto Nafion-H (a superacidic perfluorinated resinsulfonic acid). ... 

By analogy to the initial work on trifluoromethyl ketones as ZBGs in their hydrated forms [34], as in compounds 12, silanol versions 13 have been developed. HDAC1 and 8 assays are mentioned in the patent application, but activities are not stated, nor is there any indication of whether the compounds suffer similar metabolic liabilities [35]. 

Initial investigations in the Mannich-type reaction of silyl enolates with benzal-dehyde and aniline employed a series of bismuth(III) salts (Scheme 9, Table 10). These results were promising because the corresponding (l-amino ketone could be obtained in moderate to good yield with bismuth halides, except bismuth fluoride (Table 10, entries 1 1). Bismuth nitrate smoothly afforded the expected product (Table 10, entry 5). While bismuth acetate gave no conversion, bismuth trifluor-oacetate provided the product in only moderate yield (Table 10, entries 6 and 7). Phenyl bismuth ditriflate and diphenyl bismuth triflate appeared to be more efficient catalysts than all those previously tested (Table 10, entries 8 and 9). Bismuth(III) triflate led to the expected product in a good yield and in a short reaction time, without any difference between the anhydrous and the hydrated form (Table 10, entries 10 and 11). 

By contrast, the keto forms of the ketoses seem to be hydrated to only a slight extent, if at all. When the proportion of the keto form is 5% or more, as it is for the 1-deoxyhexuloses, the hydrated form should be readily detectable ip the -n.m.r. spectrum, but it has not been found. A model compound, l-deoxy-3,4,5,6-tetra-0-methyl-D-fructose, shows only the signals of the keto form in aqueous solution.16 Ketones are, on the whole, hydrated to a lesser extent than aldehydes77 in the case of ketoses having more than four carbon atoms in the chain, there would also be a 1,3-parallel interaction of one of the geminal hydroxyl groups with another hydroxyl group. 

Peptidyl fluoromethyl ketones are widely used as fairly potent inhibitors for a variety of proteases, including serine, cysteine, and aspartyl proteases. Unlike other halomethyl ketones (Section 15.1.3), fluoromethyl ketones are reversible transition-state mimics. The electron-withdrawing fluorine(s) next to the carbonyl group enhances the electrophilicity of the a-fluoroalkyl ketone functionality, thereby making the carbonyl more susceptible to nucleophilic attack. a-Fluoroalkyl ketones are good mimics of peptide bonds due to the small size of the fluorine and the stability of C F bonds. There are three general classes of peptidyl fluoromethyl ketones fluoromethyl ketones (irreversible inhibitors of cysteine proteases), difluoromethyl ketones (reversible inhibitors of both serine and aspartyl proteases), and trifluoromethyl/perfluoroalkyl ketones, which typically exist in hydrated forms and are excellent inhibitors of both serine and cysteine proteasesJ1 ... 

The most effective commercially available form of this desiccant is the monohydrate a cheaper grade contains from 30 to 40 per cent of water but this retains useful desiccating action (the fully hydrated form is the heptahydrate). It is an excellent neutral desiccant, rapid in its action, chemically inert and fairly efficient, and can be employed for most compounds including those (e.g. esters, aldehydes, ketones, nitriles, amides) to which calcium chloride is not applicable. 

The oxidation may proceed through the hydrated form of the carbonyl group > CH(OH)2. The rate of oxidation is 1,2-glycols > a-hydroxy aldehydes > a-hydroxy ketones > a-hydroxy acids. 

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. 

Ketones and aldehydes have electrophilic carbonyls that significantly contribute to the chemistry of these functional groups. In general, aldehydes tend to be more electrophilic and will often exist in aqueous solutions in hydrated form as a gem-diol (Fig. 20). This is an important consideration when attempting to characterize by NMR an unknown that may contain an... 

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. 

The catalytic oxidation of cyclohexane is performed in the liquid phase with air as reactant and in the presence of a catalyst. The resulting product is a mixture of alcohol and ketone (Table 1, entry 12) [19]. To limit formation of side-products (adipic, glutaric, and succinic acids) conversion is limited to 10-12 %. In a process developed by To ray a gas mixture containing HC1 and nitrosyl chloride is reacted with cyclohexane, with initiation by light, forming the oxime directly (Table 1, entry 12). The corrosiveness of the nitrosyl chloride causes massive problems, however [20]. The nitration of alkanes (Table 1, entry 13) became important in a liquid-phase reaction producing nitrocyclohexane which was further catalytically hydrated forming the oxime. 

The combination of Lewis add and nucleophile activations in 12-14 requires four-membered ring transition states. Interestingly, the mechanism for carboxypeptidase A (CPA) catalyzed hydrolysis of peptides also appears to involve joint Lewis add and nucleophile activations that lead to the formation of a four-membered ring transition state. Christianson and Lipscomb [57] have determined the crystal structure (15) of a ketone bound to CPA. Surprisingly, the ketone is in its hydrated form with both oxygens of the gem-diol bound to the active-site zinc of CPA (Figure 6.12). 

Aldehydes are more likely than ketones to form stable hydrates. The electrophilic carbonyl group of a ketone is stabilized by its two electron-donating alkyl groups, but an aldehyde carbonyl has only one stabilizing alkyl group. The partial positive charge of the aldehyde is not as well stabilized. Aldehydes are thus more electrophilic and less... 

The first equivalent of the organolithium reagent simply deprotonates the acid. The second equivalent adds to the carbonyl to give a stable dianion. Hydrolysis of the dianion (by adding water) gives the hydrate of a ketone. Because the ketone is formed in a... 

This reaction, like the cyanohydrin formation we discussed at the beginning of the chapter, is an equilibrium, and is quite general for aldehydes and ketones. But, as with the cyanohydrins, the position of the equilibrium depends on the structure of the carbonyl compound. Generally, the same steric factors (pp. 138-139) mean that simple aldehydes are hydrated to some extent while simple ketones are not. However special factors can shift the equilibrium towards the hydrated form even for ketones, particularly if the carbonyl compound is reactive or unstable. 

The fluorogenic hydroxyketone 14 discussed above (Scheme 1.4) can also be used to form esters such as 26 which can be used as fluorogenic substrates for lipases [37]. In this case, however, the esters are quite unstable despite being ali-phahc alcohol esters. The relatively rapid spontaneous hydrolysis in this case is probably due to an assisted mechanism involving acyl transfer in the hydrated form of the ketone. 

Trifluoroacctatc esters react with diazomethane without a catalyst to form 1-alkoxy-l-trifluoro-methyloxiranes. They are easily hydrolyzed and the a-hydroxy ketones thus formed dimerize to give 1.4-dioxanes. Heating pyruvamides (or the hydrated forms) 10 with diazo compounds 11 in toluene gives, in all cases, epoxides 12 as a mixture of diastereomers (75 25). - ... 

The carbanions derived from acylthiophenes have been condensed with aldehydes, -" and, through the Claisen condensation with esters, thienylsubstituted j8-diketones have been obtained. 2-Thenoyl trifluoroacetone, first prepared by Reid and Calvin through the Claisen condensation of 2-acetylthiophene with ethyl trifluoracetate, has become an extremely useful chelating agent for the extraction of numerous elements from strongly acidic solutions. The tautomeric form which dominates in aqueous solution is the ketone hydrate. Other thiophenes have also proved useful for analytical purposes. - ... 

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