Halogenation / dehydrohalogenation

The halogenation-dehydrohalogenation of ketones and their derivatives is the most widely applied method for the preparation of unsaturated ketones, and the different combinations of alternatives which exist for both steps extend the scope of this approach. Consequently, this route will be discussed in considerable detail. 

In 1980 Sonogashira reported a convenient synthesis of ethynylarenes - the Pd-catalyzed cross-coupfing of bromo- or iodoarenes with trimethylsilylacetylene followed by protiodesilylation in basic solution [15]. Prior to this discovery, formation of terminal acetylenes required manipulation of a preformed, two-carbon side chain via methods that include halogenation/dehydrohalogenation of vinyl- and acetylarenes, dehalogenation of /1,/1-dihaloalkenes, and the Vils-meier procedure [ 14]. With the ready availability of trialkylsilylacetylenes, the two-step Sonogashira sequence has become the cornerstone reaction for the construction of virtually all ethynylated arenes used in PAM and PDM synthesis (vide infra). 

Different procedures of this dehydrogenation are thoroughly discussed in the monograph (4). It is only necessary to note here that the process is carried out mainly as halogenation-dehydrohalogenation. The intermediate hydroximoyl halide is frequently not isolated (Scheme 1.3). The reaction is convenient for both the generation of unstable nitrile oxides (in the presence of a dipolarophile) and the preparation of stable nitrile oxides. It is usually carried out in a two-phase water-organic solvent system with methylene dichloride as the preferred solvent. 

Ring closure by an intramolecular acylation reaction followed by a halogenation-dehydrohalogenation sequence (equation 70) may account for the isolation of the... 

Azlactone oxidation Azlactones derived from dipeptides are more readily dehydrogenated than the dipeptides. This route to dehydropeptides has been examined with several reagents. Halogenation dehydrohalogenation is possible, but yields at best are 50%. Various oxidation procedures are about as effective. The most satisfactory method is oxidation of the corresponding trimethylsilyl enol ether with DDQ. However, this oxidation is limited to aryl azlactones. 

The necessary vicinal dihalides are themselves readily available by addition of Bi2 or CI2 to alkenes. Huts, the overall halogenation/dehydrohalogenation sequence makes it possible to go from an alkene to an alkyne. For example, diphenylethylene is converted into diphenylacetylene by reaction with Bt2 and subsequent base treatment. 

Halogenation-dehydrohalogenation Synthesis of an tilkyne through att alkenyl halide intermeiliate. 

Halogenation-dehydrohalogenation Synthesis of an alkyne through an alkenyl halide intermediate. Hantzsch pyridine synthesis Condensation of two 3-dicarbonyl molecules, an aldehyde, and ammonia... 

Tetraphenylallene 17, one of the first carbon-rich allenes, was produced in the early 1900s by Vorlander and Siebert via halogenation/dehydrohalogenation of phenyl-substituted olefin 18 (Scheme 1.6) [18]. This classical method set a standard for the preparation of arylallenes as the resultant product could not isomerize due to lack of an abstractable hydrogen [Id]. 

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