Favorsky reaction

The Favorsky reaction should be considered a general method for producing pyrazolyl-Q -acetylenic alcohols because even the less reactive 4-ethynyl-l,3,5-trimethylpyrazole, additionally deactivated by three donor methyl groups, reacts with acetone (Scheme 61). 

The high reactivity of monosubstituted acetylenes in many reactions (acetylenic condensation, Favorsky reaction, Mannich reaction, oxidative coupling, etc.) is determined by their acidity (7IMI1 83MI1). The literature data on the thermodynamic CH acidity of these compounds are rather scarce. 

Tertiary alkoxyenyne alcohols 114, easily prepared from alkoxyenynes and ketones by the Favorsky reaction (74ZOR1835), give, with hydrazine and alkylhy-drazines in an acidic medium, 3(5)-substituted dialkylvinylpyrazoles 115 in 80% yield(81H146). 

This procedure is the method of choice for the preparative chemist, since it not only provides the advantage of generally good yields (40—60%), but also can be carried out on a large scale. The modified Favorski reaction of dibromoketones offers a remarkably wide scope of application and has made possible the preparation of a large number of dialkyl-, diaryl-, and monoaryl cyclopropenones (see Table 1). Interestingly, the bicyclic cyclopropenones 5943) and 4041 have become accessible by use of the dibromoketone method. 

In the Favorski reaction [8], etbyne is coupled with a carbonyl compound in the presence of powdered alkali hydroxide suspended in an organic solvent, in which the acetylene has good solubility. Some acetylenic carbinols, derived from ketones, can be obtained in high yields by introducing acetylene at atmospheric pressure. The active intermediate possibly is a metal acetylide formed in low concentration. 

In an H2O/DMSO medium (1 2 by volume) tertiary acetylenic alcohols are formed from ketoximes and acetylene in yields of up to 50% (76ZOR1180), i.e., in this case the authors encountered an analog of the Favorsky reaction (cf. Section III.G). 

Terminal acetylene by potassium-bydroxide-catalyzed retro-Favorsky reaction [160b] [Eq. (39)]... 

Studies of the Favorsky reaction have shown that it is stereospecific in the nonpolar solvents ether and 1,2-dimethoxyethane but nonstereospecific in polar methanol. ... 

Quasi-Favorsky reaction. Reaction of 4(e)-bromoadamantanone (1) with silver perchlorate in water-acetone (1 2) gives only minor amounts of the expected 4-hydroxyadamantanone (3), the major product being bicyclo[3.3.1]nonene-2-car-... 

Reaction with adamantanone. Japanese chemists1 treated adamantanone (1) with sodium azide in methanesulfonic acid with the expectation of achieving the Schmidt reaction. However, the unexpected 4-methylsulfonoxyadamantanone was obtained in 90% yield. Alkaline hydrolysis cleaves (2) to A2-bicyclo[3.3.1]-mmcnc-7-carboxylic acid (3) in 85% yield by a quasi-Favorsky reaction. Adaman-lanc itself does not undergo this unusual substitution reaction. 

The Favorsky reaction, the interaction between terminal acetylenes and carbonyl compounds in the presence of powdered dry KOH, is of limited importance for the pyrazole series, although the hydroxyacetylenic group is one of the most important protecting groups. However, most often, such an alcoholacetylenic substituent is introduced by direct alkynylation of the corresponding iodopyrazoles with... 

TABLE XXn. Ethynyl- and Polyethynylpyrazoles Prepared by Retro-Favorsky Reaction [69IZV2546 69KGS1055 71IZV1764 72IZV2524 86TH1 88M253]. 

Cyclohydration of alkoxyIvinylacetylenic alcohols 180 (prepared from methoxy-butenyne by the Favorsky reaction) leads to dihydropyran-4-ones 181-183 xmder conditions of the Kucherov reaction (75MI1 88MI1 93MI2). 

A mechanism analogous to that of the Favorsky reaction is presumably involved in the methoxide-induced ring contraction of (116) to give i -lactams. ... 

Tertiary acetylenic alcohols or their ether derivatives may be usefully exploited in both Castro and Cadiot-Chodkiewicz reactions. In these cases, base-catalyzed retro-Favorsky reactions can be employed to liberate the required terminal acetylenes from the alcohol products [16]. A concise account of Chodkiewicz s contributions to this method are given elsewhere (ref. 9b, pp. 622-3). Further examples are shown in Fig. 1.11. 

CMejOH stable stable stable use Thp ether stable may be removed by retro-Favorsky reaction. (use K2CO3)... 

As for various catalytic activity of alkali metal hydroxides, it should be noted that this effect is not unique for this reaction and is observed in almost all base-catalytic processes involving alkalis, for example, vinylation reaction [5,6,109,152,166], nucleophilic substitution and elimination [153], Favorsky reaction [167], synthesis of divinyl sulfide from acetylene and alkali metal sulfides [168], and cyclization of cyanoacetylenic alcohols [169]. For instance, in vinylation of 2-ethoxyethanol with acetylene in the presence of different hydroxides, the following relative reaction rates are observed [109,152] ... 

Tertiary acetylenic alcohols (in up to 50% yield [175]) are formed from ketoximes and acetylene in aqueous DMSO. This is hitherto unknown analog of the Favorsky reaction (see Section 1.5.5). 

Like the pyrrole synthesis, the assembly of 4-methylene-3-oxa-l-azabicyclo[3.1.0]hexanes is likely triggered by the formation of O-vinyl oxime (detected by GLC and NMR). The deprotonation of O-vinyl oxime in a-position relative to the oxime function and the further intermolecular nucleophilic substitution of the vinyloxy group can lead to azirine A (Scheme 1.178). The latter reacts with acetylene (in the form of carbanion) to give acetylenic ethynyl aziri-dine B (the nitrogen analog of the Favorsky reaction), which is added to the third... 

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