Secondary from ketones

A general one-step method for preparation of primary and secondary nitroparaffins from amines by oxidation with y -chloroperbenzoic acid in 1,2-dichloroethane has been reported (68). This method is particularly useful for laboratory quantities of a wide variety of nitroparaffins because a large number of amines are readily available from ketones by oxime reduction and because the reaction is highly specific for nitroparaffins. 

C. Secondary Reactions in Enamine Formation from Ketones and Amines. ... 

The most versatile method for preparing enamines involves the condensation of aldehydes and ketones with secondary amines [Eq. (1)]. Mannich and Davidsen (/) discovered that the reaction of secondary amines with aldehydes in the presence of potassium carbonate and at temperatures near 0° gave enamines, while calcium oxide and elevated temperatures were required to cause a reaction between ketones and secondary amines, although usually in poor yield. The introduction by Herr and Heyl 2-4) of the removal of the water produced in the condensation by azeotropic distillation with benzene made possible the facile preparation of enamines from ketones and disubstituted aldehydes. 

The intermediacy of an aminal in the formation of enamines from ketones and secondary amines is not usually proposed. The only direct evidence for this is the infrared spectra of the reaction mixtures produced when dimethyl-or diethylamine was allowed to react with cyclohexanone or cyclopentanone... 

While enamines can usually be obtained directly from ketones and secondary amines their formation by an indirect route may bo advantageous. The previously mentioned condensation of rnethyl ketones during azeotropic enamine formation has prompted the alklyation (J) or acylation and reduction (59) of Schiff s bases. A parallel method uses the formation and desulfurization of N-acylthiazolines followed by hydride reduetion (60,61). 

Many impurities are present in commercial caprolactam which pass into the liquid wastes from PCA manufacture from which caprolactam monomer may be recovered. Also, the products of die thermal degradation of PCA, dyes, lubricants, and other PCA fillers may be contained in the regenerated CL. Identification of die contaminants by IR spectroscopy has led to the detection of lower carboxylic acids, secondary amines, ketones, and esters. Aldehydes and hydroperoxides have been identified by polarography and thin-layer chromatography. 

The coupling of a secondary alcohol 1 with a primary alcohol 2 is achieved by the temporary removal of from each substrate which generates the ketone 3 and aldehyde 4 intermediates. A crossed aldol condensation occurs under the reaction conditions by the enolate derived from ketone 3 undergoing nucleophilic addition... 

Preparation of enantiomerically pare secondary amines by catalytic asymmetric hydrogenation or hydrosilylation of imines is as important as the preparation of alcohols from ketones. However, asymmetric hydrogenation of prochiral ON double bonds has received relatively less attention despite the obvious preparative potential of this process.98... 

One way to create a carbon-carbon bond is to react a Grignard reagent with a carbonyl compound. The result of this reaction is an alcohol derived from an aldehyde. Formaldehyde gives a primary alcohol, but any other aldehyde gives a secondary alcohol. Ketones and esters both react to form tertiary alcohols. 

A much more generally useful process was developed by Robinson to prepare cyclohexenones from ketones and methyl vinyl ketone or its derivatives. Again, because good compilations of the Robinson annulation exist,8 only a few examples are given here. The first step of this process, the Michael addition, is carried out by normal base catalysis, while the second step, the aldol condensation, is best accomplished by the use of a secondary amine to form the enamine of the acyclic ketone, which then cyclizes... 

The metal lias to a great extent replaced zinc, which was used in 1849 by Frankland in the preparation of paraffin hydrocarbons and the zinc alkyls, and subsequently by Wagner for preparing secondary alcohol from aldehydes, by Saytzeff in preparing tertiary alcohols from ketones, and by Butlerow iu the preparation of both ketones and tertiary alcohols from acid chlorides. 

The reaction of aldehydes and ketones with Grignard reagents is a useful method of synthesising primary, secondary, and tertiary alcohols (Following fig.). Primary alcohols can be obtained from formaldehydes, secondary alcohols can be obtained from aldehydes, and tertiary alcohols can be obtained from ketones. The reaction involves the formation of a carbon-carbon bond and so this is an important way of building up complex organic structures from simple starting materials. 

Aldehydes and ketones when reduced yield alcohols with a hydride ion that is provided by reducing reagents like sodium borohydride or lithiumborohydride. Primary alcohols are obtained from aldehydes and secondary alcohols from ketones. 

Sec. 19.8) from ketones or aldehydes by reaction with secondary amines... 

Besides the initiation with the vinyl ether adducts, trimethylsilyl halides in conjunction with oxolane [135] or a carbonyl compound [136-141] also provide an interesting method of end-functionalization. As discussed in Chapter 4, Section V.E.2 (also Figure 9 therein), the a-end group is (CH3)3SiO—, derived from the silyl compound, to be converted into the hydroxyl group [140,141], Depending on the structure of the carbonyl compounds, it is either secondary (from aldehyde) [136-139] or tertiary (from ketone) [137,138,140,141], both of which are difficult to obtain from the vinyl ether adducts (note that the adduct of AcOVE leads to a primary alcohol [30,31]). 

Primary and secondary aUcyltetrasulfanes may be prepared from ketones via hydrazones by reaction with H2S (equations 70 and 71). The mechanism and stoichiometry of equation (71) are unknown, but MeC02H and 2NH4+ are probably formed as by-products, in which case four equivalents of H2S are needed, resulting in a tetrasulfane. 

This method is widely used for the preparation of secondary alcohols from ketones. The reduction of aldehydes is important only when these substances are readily available, e.g., heptanal and furfural. 

Unsymmetrical secondary amines are readily prepared in good yields by the catalytic reduction of Schiff bases at moderate temperatures in high-or low-pressure equipment. Many examples have been cited. The intermediate imines are prepared from primary amines and aldehydes—very seldom from ketones—and may be used without isolation (cf. method 431). For the preparation of aliphatic amines, e.g., ethyl-w-propylamine and n-butylisoamylamine, a prereduced platinum oxide catalyst is preferred with alcohol as the solvent. Schiff bases from the condensation of aromatic aldehydes with either aromatic or aliphatic amines are more readily prepared and are reduced over a nickel catalyst. In this manner, a large number of N-alkylbenzylamines having halo, hydroxyl, or methoxyl groups on the nucleus have been made. Reductions by means of sodium and alcohol and lithium aluminum hydride have also been described,... 

The iron carbonyl-promoted reaction of secondary dibromo ketones and an amide produces 3(2//)-fu-ranone derivatives (69) (equation 36). This cyclocoupling reaction has some useful applications, such as the synthesis of a muscarine analog (70) from furanone (71) (equation 57). Reaction of the dibromo ketone (72) with A(-methylpyrrolidinone results in formation of the aminofuranone (73) via an intramolecular deamination (equation 58). 

The hydroxy acids obtained from aldehydes will contain the group,. —CH(OH) —COOH, and are thus secondary alcohols while those obtained from ketones will contain the group, =C(OH) —COOH, and are tertiary alcohols. These reactions are of especial importance in connection with the poly-hydroxy aldehydes and ketones, which, as we shall find, are the sugars. The cyan hydrines, or hydroxy acid nitriles, which are the intermediate products in these reactions, are not isolated as such, the reaction being completed without interruption. 

Certain biotransformation processes are reversible, and formation of an inactive metabolite that can be converted back to the active drug delays the removal of the drug from the body and probably prolongs the duration of exposure of the target tissues to the drug. The common processes that can contribute to this phenomenon are oxidation/reduction of secondary alcohols/ketones, sulfides/sulfoxides, and tertiary amines/N-oxides, all of which are reversible processes. 

Potassium ruthenate, K2RUO4, is prepared in situ from ruthenium trichloride and aqueous persulfate. The reagent catalyzes persulfate oxidations of primary alcohols to acids, secondary to ketones, and primary amines to nitriles or acids at room temperature in high yields [196],... 

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