Darzens procedure

A variety of other functional groups may be present in either the halide or the mercaptan. Olefinic sulfides are obtained by the action of allyl halides on benzyl or phenyl mercaptides. Ethylene, tri-methylene, and 1-pentene chlorohydrins give hydroxyalkyl sulfides, from which chloroalkyl sulfides are obtained by the Darzens procedure (method 33) i -i pbenacyl chloride gives keto sulfides of the type CjHsCOCHjSR. Alkylmercapto acids are prepared from either halo acids... 

Brooks and Snyderi used the Darzens procedure in the conversion of tetra-hydrofurfuryl alcohol into the chloride. 

Scheme 30 illustrates a novel rearrangement process brought about through participation of the Darzens procedure . ... 

Variations in the Darzens procedure include the generation, from one phosphorylated carbanion, e.g. 359, of a second carbanion, 360 (similar to 358 already encountered in Scheme 30), as a prelude to the Darzens displacement to give 361W en treated with tetrabutylammonium cyanide, the ester 362 yields both the epoxide 363 and the cyanooxo ester 364". ... 

When malonate 9 is treated with polyphosphoric acid at room temperature, formation of lactone 11 is observed, similar to the Darzens procedure with the use of sulfuric acid. The structure of lactone is being retained during subsequent hydrolysis and decarboxylation of the exocyclic ester group followed up treatment with anhydrous hydrogen fluoride gives dimethyl tetrahydronaphthalene carboxylic acid 12. Hydrolysis and decarboxylation of 10 under standard conditions gives the same product 12. ... 

Although the standard Darzens procedure is successful for the synthesis of a wide variety of epoxides [e.g. (110), (111), and (112)], it does, however, fail when acetaldehyde and monosubstituted acetaldehydes are employed,... 

Darzen s procedure org chem Preparation of alkyl halides by refluxing a molecule of an alcohol with a molecule of thionyl chloride in the presence of a molecule of pyridine. dar-zonz pr3,se- 3r ... 

There are many routes available for the synthesis of aziridine 2-carboxylic acids, however there are few reactions which yield enantiomerically pure products. These compounds (especially those with cis-stereochemistry) are especially useful for the synthesis of bioactive molecules556. There is thus significant effort in this area of synthesis557,558, but most methods are lengthy multistep procedures. Recently, a simple, one-pot procedure, utilizing imines, has been developed for the asymmetric synthesis of c/s-N-substituted aziridine-2-carboxylic acids via a Darzens-type reaction (equation 154)559. 

The condensation of aldehydes and ketones with ethyl chloroacetate in the presence of sodium ethoxide or sodium amide produces a,/3-epoxy esters (Darzens). The scope, limitations, typical experimental procedures, and examples have been given. Briefly, aliphatic and aromatic ketones, and aromatic aldehydes react satisfactorily, whereas aliphatic aldehydes give poor yields. a-Halopropionic and a-halobutyric... 

Synthesis of glycidic esters. The Darzens reaction1 fails with compounds such as acetaldehyde which give only self-condensation products. Borch2 has described a new procedure which is generally applicable. The a-bromo ester anion (2) is smoothly generated by reaction with lithium bis(trimethylsilyl)amide in THF at —78°. Addition of the aldehyde or ketone at —78° followed by workup affords the corresponding... 

An interesting alternative procedure for the generation of Darzens intermediates is illustrated in equation (26). In this method such anions are generated by the conjugate addition of a nucleophile to an activated alkene. In the presence of a carbonyl compound, an epoxide is formed. This process has been developed as an annulation procedure. 

A procedure has been developed which extends the Darzens synthesis to the preparation of aziridine esters and amides (equation 29). Reaction of benzalaniline (80) and ethyl chloroacetate (in BuKDK/DME) results in the formation of the trans-aziridine (82a) in 29% yield analysis of the crude reaction mixture showed no more than 10% of the isomeric cis adduct (83a). Similarly, condensation of 2-chloro-N,N-diethylacetamide and (80) affords aziridines (82b) and (83b) in 65% yield. However, in this case the cis isomer predominates ( 90 10, cis trans). The formation of (83a R = OEt) as the major product is consistent with the overlap control model suggested by Zimmerman. Apparently, the decreased stability of the amide (81b) enolate relative to the ester (81a) enolate causes ki (cyclization) to become greater than k (addition Scheme 19) it follows that the stereochemical outcome is determined in the initial aldol step, and steric arguments are advanced to explain this outcome. 

Normally, the Darzens reaction of simple a-halo esters is carried out under anhydrous conditions, since in aqueous media or under phase-transfer catalysis conditions the esters are prone to hydrolysis. Saponification can be largely prevented by using r-butyl esters, but this strategy also poses potential problems, as hydrolysis of the resulting glycidic ester is often the next stage of a synthetic process. Recently, a procedure has been developed in which a-chloro esters are deprotonated by treatment with potassium... 

When the epoxide is made from a carbonyl compound, e.g. (29) (Chapter 30), the result is chain extension to the homologous aldehyde. This procedure can be carried out with sulphur ylids (30) or by the Darzens reaction with decarboxylation of the intermediate acid (31). 

The a-chloroacetic acid ester of the readily available (lS,2f )-l-A ,A-dimethylaminoinda-nol 27 was reacted with potassium t-butoxide and p-anisaldehyde to give the Darzens condensation product 28 as an 89 11 mixture of diastereoisomeric epoxides. The one reported in the figure is the major component of the mixture and has the required (2R,3S) configuration. Treatment with 2-amino-thiophenol at 120 °C led to adduct 29 from which 26 was eventually obtained by known procedures. 

This procedure can also be used in Darzens condensations ... 

At the same time, Antilla et al. developed a vaulted biphenanthrol (VAPOL)-based magnesium phosphate 20b mediated asymmetric aza-Darzens reaction for the synthesis of chiral aziridine derivatives. The catalyst was prepared in an identical procedure to the previously described process with VAPOL-derived phosphate and magnesium fert-butoxide, and applied in the enantioselective aza-Darzens reaction of N-benzoyl imines 23 and ot-chloro-1,3-diketone 24. The process formed a series of substituted aziridines 25 bearing various substituents at the aromatic ring, with good... 

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