Pyrazoline electrophilic reactions

In the case of 1,5-disubstituted pyrazolines, electrophilic reaction involves position 3. 

The features of the electronic structure of aryl-substituted pyrazolines influence their chemical properties. For example, in the case of 3-substituted 7V-phenyl-pyrazolines 100 reactions of formylation, acylation, nitration, sulfonation, azocoupling and other electrophilic processes involve the para position of the 7V-phenyl ring, with formation of compounds 101 [103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113]. On the other hand, some electrophilic reactions, including nitration, bromination, chlorination, formylation and azocoupling, for 3-unsubstituted pyrazolines 102 occur at position 3, yielding heterocycles 103 and in some cases as a mixture with 104 [108, 114, 115] (Scheme 2.26). This fact provides evidence for orbital control of these reactions. 

The recently reported (757) conversion of 5-pyrazolones directly to a,j8-acetylenic esters by treatment with TTN in methanol appears to be an example of thallation of a heterocyclic enamine the suggested mechanism involves initial electrophilic thallation of the 3-pyrazolin-5-one tautomer of the 5-pyrazolone to give an intermediate organothallium compound which undergoes a subsequent oxidation by a second equivalent of TTN to give a diazacyclopentadienone. Solvolysis by methanol, with concomitant elimination of nitrogen and thallium(I), yields the a,)S-acetylenic ester in excellent (78-95%) yield (Scheme 35). Since 5-pyrazolones may be prepared in quantitative yield by the reaction of /3-keto esters with hydrazine (168), this conversion represents in a formal sense the dehydration of /3-keto esters. In fact, the direct conversion of /3-keto esters to a,jS-acetylenic esters without isolation of the intermediate 5-pyrazolones can be achieved by treatment in methanol solution first with hydrazine and then with TTN. 

As it is known from experience that the metal carbenes operating in most catalyzed reactions of diazo compounds are electrophilic species, it comes as no surprise that only a few examples of efficient catalyzed cyclopropanation of electron-poor alkeiies exist. One of those examples is the copper-catalyzed cyclopropanation of methyl vinyl ketone with ethyl diazoacetate 140), contrasting with the 2-pyrazoline formation in the purely thermal reaction (for failures to obtain cyclopropanes by copper-catalyzed decomposition of diazoesters, see Table VIII in Ref. 6). 

Thus, several general conclusions about the reactions of pyrazolines with electrophilic reagents can be made ... 

Reactions of pyrazoline derivatives with electrophilic reagents very often become complicated owing to the oxidative destruction and/or processes related to the C5—Ni bond breaking. 

Due to the electrophilic character of carbenes. they are not expected to easily react with electron-poor alkenes, and the only reported examples concern reactions with diazo compounds (i.e., diazomethane, diazofluorcnc. ethyl diazoacetate. and phenyldiazoniethane ). However, depending on the reaction conditions, carbenes arc not always the reactive species. Cyclopropanes are often obtained by decomposition of pyrazolines which arise from 1,3-dipolar cycloaddilion reactions (see Section 2.1.1.6.2.3.1.). Even when reactions are performed under irradiation, pyrazolines can be obtained as the result of a diradical addition. ... 

The electrophilic cyclopropane 59 is prepared according to a reaction scheme which involved the photolysis of ethyl diazoethylidenecyanoacetate (56) to give the cyclopropene (57) derivative which in turn on addition of diphenyldiazomethane afforded the bicyclic pyrazoline (58). Thermolysis of 58 produced bicyclo[ 1.1.0]butane derivative 59 (equation 9). ... 

Chiral electrophilic cyclopropanes (63) are prepared in high enantiomeric excess starting from butadiene-iron tricarbonyl complexes (60) containing a non-complexed double bond. Reaction with diazomethane and decomposition of the resulting pyrazolines (61) in the presence of Ce" gave the corresponding chiral cyclopropanes (62). Breakdown of the dienic substituent of electrophilic cyclopropane (62) by means of ozonization resulted in the formation of formyl-substituted electrophilic cyclopropane (63) still carrying the asymmetric centre (equation 10) " . ... 

The iodoaminocyclization of hydrazones proceeded under very mild conditions to generate pyrazolines with high selectivity (Scheme 7.33 and Example 7.13) [56]. The organocataly tic reaction was promoted by the use of a bifunctional thiourea catalyst Using A -iodopyrrolidinone as the source of electrophilic iodine leads to the highest selectivity for the reaction. Control reactions were carried out and the authors noted that strict control of the temperature was needed to prevent a background reaction. Additionally, including molecular sieves in the reaction mixture led to an increase in the selectivity. 

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