Wallach procedure

Wagner equation Wagner number Wakamatsu reaction Waldhof fermentor Walkman Wallace plasticity Wallach procedure Wall baffles Wallboard Wall geometries Wallpaper paste Wallpaper pastes Wallpapers Wall plaster Walnut oil... 

The discovery of the Balz-Schiemann reaction in 1927 replaced the earlier Wallach procedure (1886) based on fluorodediazoniation of arenediazonium piper-idides (aryltriazenes) in aqueous hydrogen fluoride [40 41]... 

The Leuckart-Wallach procedure is not very suitable for use with lower aliphatic ketones. However, acetophenone and similar higher-boiling ketones afford the primary amines in 70-80% yield when treated with the mixture of ammonium formate and formamide (the Ingersoll reagent) that is formed when ammonium formate or an ammonium carbonate-carbamate mixture is heated with formic acid at 165°.1022... 

The present procedure was developed from those of Wallach and Freylon, based upon the general method discovered by Leuckart. a-Phenylethylamine also can be prepared satisfactorily by the reduction of acetophenone oxime with sodium and absolute alcohol or sodium amalgam, but the reagents are more expensive and the processes less convenient. The amine has been obtained by reducing acetophenone oxime electro-lytically, by reducing acetophenone phenylhydrazone with sodium amalgam and acetic acid, from a-phenylethyl bromide and hexamethylenetetramine, and by the action of methyl-magnesium iodide upon hydrobenzamide, as well as by other methods of no preparative value. 

The usual procedure is to simply heat a mixture of the starting materials. A common side-reaction is the polyalkylation it can be suppressed by employing an excess of amine. In addition carbonyl substrates with a-hydrogens may undergo competitive aldol reactions the corresponding reaction products may then undergo a subsequent Leuckart-Wallach reaction. 

Pr)4, " borohydride-exchange resin,and formic acid. When the last is used, the process is called the Wallach reaction. Conjugated aldehydes are converted to alkenyl-amines with the amine/silica gel followed by reduction with zinc borohydride.In the particular case where primary or secondary amines are reductively methylated with formaldehyde and formic acid, the method is called the Esch-weiler-Clarke procedure. It is possible to use ammonium (or amine) salts of formic acid, " or formamides, as a substitute for the Wallach conditions. This method is called the Leuckart reaction,and in this case the products obtained are often the N-formyl derivatives of the amines instead of the free amines. Primary and secondary amines can be iV-ethylated (e.g., ArNHR ArNREt) by treatment with NaBH4 in acetic acid. Aldehydes react with aniline in the presence of Mont-morillonite KIO clay and microwaves to give the amine. Formaldehyde with formic acid converts secondary amines to the N-methyl derivative with microwave irradiation. 

The reductive alkylation of amines is called the Leuckart-Wallach reaction [112-115]. The primary or secondary amine reacts with the ketone or aldehyde. The formed imine is then reduced with formic acid as hydrogen donor (Scheme 20.27). When amines are reductively methylated with formaldehyde and formic acid, the process is termed the Eschweiler-Clarke procedure [116, 117]. 

Interestingly, Wasserscheid et al. have developed an efficient method to prepare TSOS derived from alkaloids such as ephedrine or amino alcohols such as valinol. In both cases, TSOS were obtained on the kilogram scale using a three step procedure (Leuckart-Wallach reaction followed by alkylation with Me2S04 and anion metathesis) [25] (Fig. 8). 

In other publications, Wallach et al.[66], Brooks et al.[731 and Kautz and Schnack-erz1401 gave detailed reports on the isolation and characterization of the dihydropyrimidinase from beef liver. Table 12.4-2 gives a short overview of the purification procedures and characteristic properties of these mammalian enzymes. The beef liver dihydropyrimidinase consists of four subunits and every active enzyme molecule contains four Zn(II)cations1731 which are tightly bound (Ks > 1.33 x 109 m 1). In addition to 5,6-dihydrouracil, glutarimide, thiohydantoin and barbituric acid are also accepted as substrates, but with low reaction rates1401. 

Recently, the application of microwave conditions to reactions that normally proceed thermally, but with long reaction times, has led to a much-hastened procedure for the Leuckart-Wallach reaction. 9 Loupy et al. have carried out the reductive amination of various aromatic ketones using a 1 3 3 ratio of carbonyl formamide formic acid under microwave irradiation for 30 minutes to produce the corresponding amines in high yields.19 In comparative studies the authors report considerable improvements in yield with microwave use. 

Among monoamines, both enantiomers of 1-phenylethylamine and their derivatives play a prominent role. They are commercially available, but can also be prepared by resolution of the racemate, obtainable by Leuckart- Wallach reaction of acetophenone1, with malic acid2 or, more conveniently, with tartaric acid in methanol3. They are used as chiral additives for the addition of zinc alkyls to aldehydes in Section D. 1.3.1.4., as copper complexes for the synthesis of biaryls in Section B.2., as lithium salts for enantioselective deprotonation in Section C., and as imines in Sections D.1.1.1.3.1., D.1.1.1,4.. D.1.4.4., D.1.5.2., D.1.5.8., D. 1.6.1.2.1., D.2.3.I., and D.8. A general procedure for the synthesis of imines from carbonyl compounds and primary amines, with many examples of both chiral carbonyl compounds and chiral amines is given in reference 4. 

The reaction of carboxylic acid amides with phosphorus pentachloride, to yield compounds I and II, was investigated extensively by Wallach and his students in 1876-1882, and later by v. Braun, who utilized this reaction to degrade secondary amines to ammonia. The highly reactive imidoyl chlorides have been used, especially by v. Braun, as synthetic tools to produce a variety of compounds which could not easily be synthesized by other procedures. However, imidoyl chlorides never made the headlines in synthetic organic chemistry, most likely because of the inherent difficulty involved in handling these highly reactive compounds. 

The thermal elimination of alkyl halides to form nitriles is perhaps the best known reaction of imidoyl chlorides. J. v. Braun investigated this reaction in detail over a period of 40 years, and he developed a host of useful new synthetic procedures for the synthesis of compounds, which are otherwise more difficult to obtain. Unfortunately, most of his work has been written up in detailed form in Chemische Berichte and it requires some effort to retrieve this information. However, he wrote one review article in 1934 which is most informative. The elimination of alkyl halides on heating of imidoyl chlorides was recognized by Wallach in 1877 and v. Pechmann and Ley and Holzweissig reported examples of this reaction prior to the work of J. v. Braun. The elimination reaction, in its most general terms, can be described by the following sequences ... 

The original synthesis discovered by Leuckart was the reductive alkylation of benzaldehyde to form benzylamine using formamide or ammonium formate as the reducing agent. This was later extended by Wallach and by the Eschweiler-Glarke procedure . The scope of the Leuckart reaction has been reviewed by Moore Apart from the special case of formaldehyde, the reaction is most focile with aromatic aldehydes and water-insoluble ketones. Aliphatic... 

The membrane protein of Ehrlich ascite carcinoma isolated through similar procedure (Zahler and Wallach, 1967) is extensively soluble in 3 M KI at neutral pH. 

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