Leusen

Many different approaches have been suggested as possible approaches to this problem, from the 1960s onwards [Verwer and Leusen 1998]. What is obvious from all of these ellorts is that this is an extremely difficult problem. Both thermodynamics and kinetics can be important in determining which crystalline form is obtained under a certain se1 of experimental conditions. Kinetic effects are particularly difficult to take into accouni and so are usually ignored. A proper treatment of the thermodynamic factors would lequire one to deal with the relative free energies of the different possible polymorphs... 

Karfunkel H R, B Rohde, F J J Leusen, R J Gdanitz, emd G Rihs 1993. Continuous Similarity Measure Between Nonoverlapping X-ray Powder Diagrams of Different Crystal Modifications. Journal oj Computational Chemistry 14 1125-1135. 

Recently Oldenziel and Van Leusen (750) have reported a new synthesis of 4-tosylthiazoles (275), R = p-MeOCgH4, p-MeCgH, Ph, p-ClCgH, and 2-furyl, from tosylisocyanide (272) and carboxymethyldi-thioates (273) (Scheme 142) yields ranged from 50 to 80%. 

CWG van Gelder, EJJ Leusen, JAM Leunissen, JH Noordik. A molecular dynamics approach for the generation of complete protein structures from limited coordinate data. Proteins 18 174-185, 1994. 

Whereas sulfonyl halides have been known for a long time and, especially the chlorides, have become of great synthetic value, sulfonyl cyanides were unknown until 1968. They were first prepared by van Leusen and co-workers from the reaction of sulfonylmethylenephos-phoranes with nitrosyl chloride. The same group also investigated part of their chemistry. Since then, two more, completely different, methods of synthesis were published from sulfinates with cyanogen chloride,and by the oxidation of thiocyanates. ... 

At present, trial-and-error proeedures of experimental sereening are usually employed. Leusen etal. (1993) hypothesized that separability eorrelates with the differenee in the internal or lattiee energy of the two diastereomer adduets and the extent to whieh moleeular modelling methods may be applied to estimate sueh energy differenees. 

The Barton-Zard (BZ) pyrrole synthesis is similar both to the van Leusen pyrrole synthesis that uses Michael acceptors and TosMlC (Section 6.7) and the Montforts pyrrole synthesis using a,P-unsaturated sulfones and alkyl a-isocyanoacetates." An alternative to the use of the reactive nitroalkenes 1 is their in situ generation from P-acetoxy nitroalkanes, which are readily prepared via the Henry reaction between an aldehyde and a nitroalkane followed by acetylation. Examples are shown later. 

The van Leusen reaction forms 5-substituted oxazoles through the reaction of p-tolylsulfonylmethyl isocyanide (1, TosMIC) with aldehydes in protic solvents at refluxing temperatures. Thus 5-phenyloxazole (2) is prepared in 91% yield by reacting equimolar quantities of TosMIC and benzaldehyde with potassium carbonate in refluxing methanol for 2 hrs. ... 

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