Pyrolysis of pyrazolines

Pyrolysis of pyrazolines in high boiling solvents such as dibutyl ether or ethylene glycol alfords only the 16-methyl-A -steroids (3). The same products are obtained by refluxing (2) in carbon tetrachloride in the presence of acidic alumina. 

Pyrolysis of pyrazolines, 102, 103 Pyrrolidine enamines, 412 2a-(N-pyrrolidinylcyanomininomethy 1) -A-nor-5a-androstan-17ftol, 415... 

In (39), we have an example of a stereospecific formation of a pyrazo-line. When pyrazolines are photolyzed, the elimination of nitrogen, if concerted, should be syn. This stereospecific product has been observed (McGreer and Wu, 1967). The pyrolysis of pyrazolines, if concerted, should be anti. It is not clear why this process turns out to be complex in (39), one alkene is formed stereospecifically by an anti hydrogen migration, but two isomeric cyclopropanes are formed. Crawford and Ali (1967), find rather different product patterns in the pyrolysis of 3-methyl and 3,4-dimethylpyrazolines, and give evidence for diradical intermediates. The general problem of unstable intermediates in a step-wise process will be discussed in a later section. 

Isolable pyrazolines (183) are obtained from the (1,3-butadiene)phosphonic acid esters (182 X=S02Me, COOalkyl R "=H or Me R2=Me or Ph) (products from (182 X=CN) are thermo-labile) and diazomethane. Pyrolysis of the phosphorylated pyrazolines affords phosphonopentadienes rather than phosphono-cyclopropanes (contrast (184)) and with NaH give pyrazoles or pyrazolephbsphonic acid esters. 

Diphenylcyclopropane has been prepared in 24% yield by the Simmons-Smith reaction,2 in 78% yield by treatment of 3,3-diphenylpropyltrimethylammonium iodide with sodium or potassium amide,3 in 61% yield by reaction of 1,1-diphenyl-ethylene with dimethylsulfonium methylide,4 and in unspecified yields from 1,1-diphenylethylene by reaction with diazomethane followed by pyrolysis of the resulting pyrazoline or by reaction with ethyl diazoacetate followed by distillation of the corresponding acid over calcium oxide.5... 

Pyrolysis of the pyrazoline butanoic acid esters 258 gave the lactams 259 (R = H, C02Et).210 Pyrazolone 260 reacted with 2,3-dimethyl-1,3-butadiene to furnish the expected cycloadduct.211... 

The first a-cyclopropyl acyl silanes to be isolated were generated by treatment of a,f-unsaturated acyl silanes with diazomethane, followed by vapour-phase pyrolysis of the intermediate pyrazoline derivatives (vide infra, Section IV.D)141. They suffer acid-induced cleavage or rearrangement under more mild conditions than do their carbon analogues146. 

The first recorded cyclopropyl acyl silane (69) was generated by vapour phase pyrolysis of a pyrazoline derived from a,/)-unsaturated acyl silane by 1,3-dipolar cycloaddition of diazomethane (vide supra, Section DTE)141. Exposure of 69 to titanium tetrachloride induced ring expansion to give the cyclobutanone in 75% yield (Scheme 113). 

The trienone (74), either by reaction with diazomethane and pyrolysis of the derived pyrazoline or by treatment with dimethylsulphoxonium methylide anion, yielded28 the 1 a,2 -methylene derivative (75). Epoxidation followed by the action of hydrogen chloride gave (77). The methylene bridge was re-formed by the reaction of collidine, the product being (76). Halogenated steroids of use in determining the metabolic fate of 16-chloro-oestrone methyl ethers and of chlormadinone acetate have been synthesized.29... 

After a brief historical recapitulation, the substantial body of experimental and theoretical work on these thermal epimerization reactions reported over the past 40 years is summarized. Of primary concern here are examples of stereomutations involving monocyclic, stereochemically unconstricted and minimally substituted molecules. Experimental studies of more heavily substituted cyclopropanes attempts to generate trimethylene diradical intermediates from pyrazolines " and the fascinating and still incompletely understood thermal chemistry of bicyclo[2.1.0]pentanes, 2-methylenebi-cyclop.l.OJpentanes", bicyclo[3.1.0]hex-2-enes and related reactions such as the pyrolysis of cyclopropane at 1200 °C to give products such as cyclopentadiene and toluene are neglected, in spite of obvious mechanistic interrelationships. 

McGreer et al. have also found a similar stereochemical reversal in the pyrolysis of cis- and /ran>3,5-dimethyl-3-carbomethoxy-A -pyrazolines which was somewhat less pronounced in the condensed phase than in the gas phase. On the other... 

Crawford, R. J., Cameron, D. M. Pyrolysis of 3-vinyl-1-pyrazoline and 3-vinyl-1-pyrazoline-5,5-d2, and its relation to the vinylcyclopropane to cyclopentene rearrangement. Can. J. Chem. 1967,45, 691-696. 

The 3,3 -bis(2-pyrazolin-5-ones) in which the rings are connected by carbon chains (Table VIII) are usually prepared by condensation of a hydrazine with an appropriate / ,/ -dioxodiester (eq. 84).419,462,1222,1225 Such bispyrazolinones linked by a carbonyl group have been prepared by pyrolysis of the calcium salt of 5-oxo-2-pyrazolin-5-one.1549... 

Numerous unsuccessful attempts to synthesize cyclopropanethione have been reported. Thermal or photochemical generation of the C3H4S species from different sources always leads to allene episulfide. Some representative experiments include (a) in vacuo pyrolysis of the sodium salt of 2,2,4,4-tetramethylthietanone tosylhydrazone (4) into the stable tetramethylallene episulfide (S), (b) pyrolytic extrusion of nitrogen from perfluorinated thiadiazoline 6, (c) in vacuo pyrolysis of spiro compound 8 into methylenethiirane (3), (d) the flash vacuum pyrolysis-microwave spectroscopic approach applied to spiro compounds 9 and 10, (e) pyrolysis of anthracene adduct 11 and tosylhydrazide salt 12, (f) thermolytic nitrogen extrusion from pyrazoline-4-thione 13, thermolysis of tetramethylallene episulfide (5) or pyrazoline 13 in dig-lyme solution, and photolytic nitrogen extrusion from pyrazoline 13, ° (g) thionation of methylenecyclopropanone 15, and (h) reaction of donor-acceptor substituted allenes 18 with elemental sulfur. ... 

The product mixtures resulting from pyrolysis of the stereoisomeric pyrazolines A and B have been compared. Both compounds give a 1 1 mixture of cis- and trans-2-deuteriomethylcyclopropane. What restrictions are placed on the mechanism by this result Formulate a mechanism that is consistent with the data. 

Stereochemical crossover in the pyrolysis of 3,5-disubstituted pyrazolines was proposed. The observation of a stereochemical crossover phenomenon stimulated a consideration of the mechanism from a different viewpoint. The loss of molecular nitrogen in the pyrolysis of a cis-3,5-disubstituted pyrazoline, cis-8, might be expected to give a trimethylene... 

Protonation reactions, 370 [Pt(dddt)2]FeCl4, 191 P-type conductors, 648 PVK-bonded dinitrophthalocyanine, 566 PVK-graft-polyisoprene, 566 Pyrazino-fused TCNQs, 246 Pyrazinotetrathiafulvalene, 170 Pyrazoline, 541 Pyridine-TCNQ, 238 Pyrolysis of polyacrylonitrile, 624 Pyromellitic dianhydride (PMDA), 92, 93 Pyropolymers, 762... 

Pyrolysis at 190° of the resulting diastereomeric A -pyrazolines (8) and (11) leads to elimination of nitrogen and formation of the cis- and tmns-cydo-propanecarboxylates (9) and (12), respectively. Thermal decomposition of the A -pyrazoline (13) affords methyl tiglate (14) in addition to the cyclopropane derivative (15) in a ratio 2 1, while A -pyrazolines such as (3) give only 0L,[i- or, y-unsaturated esters, and no cyclopropane derivatives. 

High vacuum pyrolysis, heating in organic bases, contact with acidic adsorbents and reaction at room temperature with perchloric acid or boron trifluoride etherate cleaves the pyrazoline to give a 45-60% yield of the cyclopropane derivative (13) as well as 9 % of the unsaturated methyl compound (14). ° ... 

Spiro-pyrazoline derivatives (18) are obtained smoothly from 16-methy-lene-17-ketones (17). ° The sole products formed from (18) by pyrolysis or cleavage in the presence of boron trifluoride etherate, are the 16-spiro-cyclopropyl steroids (19). ... 

Pyrazolines (51) can be converted to cyclopropane and N2 on photolysis""" or pyroiysis. The tautomeric 2-pyrazolines (52), which are more stable than 51 also give the reaction, but in this case an acidic or basic catalyst is required, the function of which is to convert 52 to 51." In the absence of such catalysts, 52 do not react/ In a similar manner, triazolines (53) are converted to aziridines." Side reactions are frequent with both 51 and 53, and some substrates do not give the reaction at all. However, the reaction has proved synthetically useful in many cases. In general, photolysis gives better yields and fewer side reactions than pyrolysis with both 51 and 53. S/Z-Pyrazoles" " (54) are stable to heat, but in some cases can be converted to... 

The pyrazoline derivative 260 was also the precursor for the synthesis (252) of the naturally occurring umbelactone. Reaction of butenolide 159c with diazomethane gave the pyrazoline 260, which was subjected to pyrolysis to give (—)-(5 )-umbelactone (261). As the natural umbelactone was described as being dextrorotatory, the synthesis of (+)-(R)-umbelactone from 159c was also performed. 

---