Hydrolysis carbonyl derivatives

Active Raney nickel induces desulfurization of many sulfur-containing heterocycles thiazoles are fairly labile toward this ring cleavage agent. The reaction occurs apparently by two competing mechanisms (481) in the first, favored by alkaline conditions, ring fission occurs before desul-, furization, whereas in the second, favored by the use of neutral catalyst, the initial desulfurization is followed by fission of a C-N bond and formation of carbonyl derivatives by hydrolysis (Scheme 95). 

Fig. 9.1. Simplified reaction mechanisms in the hydrolytic decomposition of organic nitrates. Pathway a Solvolytic reaction (Reaction a) with formation of a carbonium ion, which subsequently undergoes SN1 addition of a nucleophile (e.g., HO ) (Reaction b) or proton E1 elimination to form an olefin (Reaction c). Pathway b HO -catalyzed hydrolysis (,SN2). Pathway c The bimolecular carbonyl-elimination reaction, as catalyzed by a strong base (e.g., HO or RO ), which forms a carbonyl derivative and nitrite.

The complex is additionally stabilised by co-ordination of the phenoxide, and possibly the carboxylate, to the metal ion, illustrating the utility of chelating ligands in the study of metal-directed reactivity. We saw in the previous section the ways in which a metal ion may perturb keto-enol equilibria in carbonyl derivatives, and similar effects are observed with imines. The metal ion allows facile interconversion of the isomeric imines. The first step of the reaction is thus the tautomerisation of 5.28 to 5.29 (Fig. 5-56). Finally, the metal ion may direct the hydrolysis of the new imine (5.29) which has been formed, to yield pyridoxamine (5.30) and the a-ketoacid (Fig. 5-57). 

Aza-allyl anions also react with carbonyl derivatives to give iV-protected P-hydroxyamines and p-amino alcohols after reduction or hydrolysis.334... 

Green and co-workerii described the reaction of CO2 with Cp4MejAli M02 (281]. An MoC(0)OAJ system was formed via the insertion of carbon dioxide into an Mo-Al bond. Hydrolysis, extraction with hydrobromic acid, and the addition of aqueous hexafluoruphosphale yielded the carbonyl derivative lCp Mo(CO)Br]PF6, and the reaction of MoCpjHfMgBrCTHF) ] with CO2 yielded MoCpj(CO) (282,283]. 

Carbonyl derivatives of iron(II) exist. Pentacarbonyl-iron(O) is oxidized by halogens to give carbonyl halide complexes (equation 35). The stability of these compounds with respect to thermal decomposition and hydrolysis increases in the sequence Cl < Br < I. 

Cryptate complexes with macrobicychc hgands containing three bipy units, in which the Ln + ion is contained within a hgand cavity, have been synthesized. Such hgands will complex Ln + ions, such as Eu + and Sm +, under conditions where Ln + ions are not. An application has been using lanthanide cryptates of the early lanthanides (La, Ce, Eu) as catalysts in the hydrolysis of phosphate monoesters, diesters, and triesters. Schiff base complexes can be synthesized by the reaction of a lanthanide salt with a diamine and a suitable carbonyl derivative such as 2,6-diacetylpyridine. 

Studies using isotopic labeling as well as mechanism based on inactivation such as 4-alkyldihydropyridines and cycloalkylamines have supported the view that the first step involves an electron-transfer process (path a. Scheme 23) [18, 184-186, 211]. Deprotonation of the resultant aminium radical would yield the a-aminoalkyl radical. The formation of the dealkylated amine and carbonyl derivative has been proposed to occur via a second electron transfer to the enzyme and a nonenzymatic hydrolysis of the imine formed. In the P-450 catalyzed reaction, however this process is proposed to occur via a radical recombination process to yield a carbinolamine (99) which then decomposes to the dealkylated amine and the corresponding carbonyl derivative. Evidence for this was obtained by the incorporation of label from 02, into the carbonyl derivative [212-214]. 

Boronic acids (5a) were among the first examples of low-molecular-weight, reversible inhibitors of serine proteinases [151, 152]. Significant inhibition was initially demonstrated against a-chymotrypsin. Unlike the carbonyl-derived reversible inhibitors, which require a polypeptide or peptide-like chain, activity was found with simple alkylboronic acids (e.g. the value for PhCH2CH2B(OH)2 with a-chymotrypsin was = 40 //M) [153], Weak inhibition of elastase (PPE) was first reported for a series of arylboronic acids, for example, (10-1) [123]. Some of the boron-based inhibitors Figure 2.5) were tested as either the difluoroboranes (5b) or as the pinacol boronate esters (5c). These modifications were employed because they were more readily synthesized and/or purified than the boronic acids. For both of these derivatives inhibition was shown to be due to in situ hydrolysis to the parent boronic acid (5a) [154, 155]. 

A kinetic study of the effect of water on the hydrolysis of (173) established the existence of two reaction pathways leading to the carbonyl derivatives, depending on water concentration. The unsatisfactory results observed in many instances led to modifications of the hydrolysis conditions. The supposed limitation of the Nef reaction due to steric hindrance is probably a result of the low solubility of nitroalkanes in aqueous alkali, as demonstrated by the success of the reaction if THF-H20," alcoholic sodium hydroxide" or alkoxide" is used. Silica gel" ° as a reaction medium is of great advantage when the use of organic solvents is undesirable. A two-layer method represents an improvement for the conversion of aromatic nitroalkanes. ... 

Carbon-nitrogen double bonds exist in carbonyl derivatives, e.g. oximes. When nitrogen carries an alkyl group, the imine so formed is prone to hydrolysis. 

The enantioface selective protonation of prochiral enol derivatives is a simple and attractive route for the preparation of optically active carbonyl derivatives. Reports of stoichiometric protonation of metal enolates by a chiral proton source at low temperature leads to optical yields from 20 to 85% ee and yeast esterase catalyzes the hydrolysis of 1-acetoxycycloalkenes with enantioselectivi-ties between 41 and 96% for enol protonation [17,18]. These reactions involve enolates under basic conditions. Hydrolysis of enol ethers under acidic conditions proceeds via a rate-determining carbon protonation and is catalyzed by carboxylic acids [19,20]. Raymond et al. [21] reasoned that a complementary... 

N-Chlorocarbamate/Chromium(II) Chloride. Enol ethers (see Eq. 80) and glycals (see Eq. 84) react with N-chlorocarbamates in the presence of chromous chloride to produce a-amino carbonyl derivatives.343 Trimethylsilyl enol ethers give low yields because of their ease of hydrolysis. A radical chain mechanism has been proposed with the N-haloamide acting as the transfer agent (Eq. 32).344... 

Vilsmeier formylation of 2-benzylisoindole gives the 1-formyl derivative (61%).25 With 1-phenylisoindole reaction occurs at the unsubstituted a-position the intermediate iminium salt on neutralization gives the cross-conjugated enamine system 78, which has been isolated and characterized. X-Ray analysis confirms the assigned structure.95 On hydrolysis, the formyl derivative, which has also been the subject of X-ray crystal analysis (Figs. 4 and 5), is formed. As expected from the analogy with pyrrole chemistry, the aldehyde does not readily form typical carbonyl derivatives. 

In some cases the formation of carbonyl derivatives of the amines can reduce the useful yield.6 These products arise from the hydrolysis of the isomerised Schiff base 14. Interestingly, it has been shown that the final product is not derived from these carbonyl byproducts. Cope et al. showed that, in the case of methylation of optically active amines in which the asymmetric carbon is alpha to the amine, complete retention of configuration was... 

B.iv. Nitrile Enolates. Nitrile enolates are formed by reaction of a nitrile with LDA or another suitable base. Both alkylation 30 and condensation reactions with aldehydes 3 or ketones are known. 32 in addition to alkyl halides and carbonyl derivatives, condensation can occur with another nitrile. The base-catalyzed condensation of two nitriles to give a cyano-ketone, via an intermediate cyano enolate, is known as the Thorpe reaction. 33.109e Reaction of butanenitrile with sodium ethoxide gave a nitrile enolate, which reacted with a second molecule of butanenitrile at the electrophilic cyano carbon to give 206. Hydrolysis gave an intermediate imine-nitrile (207), which is in equilibrium with the enamine form (208, sec. 9.6.A). Hydrolysis led to the final product of the Thorpe reaction, an a-cyano ketone, 209. 33 Mixed condensations are possible when LDA and kinetic conditions are used to generate the a-lithionitrile (a mixed Thorpe reaction). When pentanenitrile was treated with LDA and condensed with benzonitrile, 2-cyano-l-phenyl-1-pentanone was the isolated product after acid hydrolysis. Nitrile enolates can also be alkylated with a variety of alkyl halides. 34... 

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