Mechanism cyclopropanone

The currently accepted mechanism for the Favorskii rearrangement of dihalo ketones involves a cyclopropanone intermediate formed by loss of HX. This is followed by attack of alkoxide synchronous with cyclopropanone fragmentation and departure of halide ion to form the unsaturated ester... 

The above mechanism would suggest that cyclopropanone formation is synchronous with an internal SN2-type displacement of halogen, with inversion. An alternate pathway assumes loss of halide ion before cyclopropanone formation to give a mesomeric zwitterion or a no bond form of a cyclopropanone which subsequently collapses to the cyclopropanone ... 

The net structural change is the same for both mechanisms. The energy requirements of the cyclopropanone and semibenzilic mechanism may be fairly closely balanced.87 Cases of operation of the semibenzilic mechanism have been reported even for compounds having a hydrogen available for enolization.88 Among the evidence that the cyclopropanone mechanism operates is the demonstration that a symmetrical intermediate is involved. The isomeric chloro ketones 12 and 13, for example, lead to the same ester. 

It has been found that the bromo ketones 10-7a-c can rearrange by either the cyclopropanone or the semibenzilic mechanism, depending on the size of the ring and the reaction conditions. Suggest two experiments that would permit you to distinguish between the two mechanisms under a given set of circumstances. 

Quantum mechanical/molecular mechanical study on the Favorskii rearrangement in aqueous media has been carried out.39 The results obtained by QM/MM methods show that, of the two accepted mechanisms for Favorskii rearrangement, the semibenzilic acid mechanism (a) is favored over the cyclopropanone mechanism (b) for the a-chlorocyclobutanone system (Scheme 6.2). However, the study of the ring-size effects reveals that the cyclopropanone mechanism is the energetically preferred reactive channel for the a-chlorocyclohexanone ring, probably due to the straining effects on bicycle cyclopropanone, an intermediate that does not appear on the semibenzilic acid pathway. These results provide new information on the key factors responsible for the behavior of reactant systems embedded in aqueous media. 

A possible mechanism for the observed transformation includes the sequence outlined in Scheme 2.327 (i) propargyl (A) - allene (B) tautomerization, (ii) 8jt-cyclization (C), (iii) N-0 cleavage (diradical D), (iv) diradical recombination (cyclopropanone derivative E), and (v) one or two step cyclizations of the azadienyl cyclopropanone into azepinone F. The occurrence of cyclopropanones (type E), as intermediates, is supported by the formation, in some cases, of isoindoles (type I) (789) as minor products (Scheme 2.327) (139, 850, 851). 

Semiempirical calculations have been used to study the mechanism of the ring opening of cyclopropanone and substituted analogues in a range of solvents of varying polarity. Transition states and oxyallyl intermediates have been characterized, as have the effects of solvents on their stability. The results are also compared with kinetic data in the literature. 

The mechanism of the novel transformation of a-nitro- to a-hydroxy-ketones has been probed. The reaction, which proceeds under basic aqueous conditions, requires that the Q -nitro substrate be CH-acidic in the a -position, and that it be readily depro-tonated under the conditions employed. NO2 -OH exchange occurs with retention of configuration, with the hydroxyl oxygen being predominantly derived from the solvent. A mechanism involving neighbouring-group participation, via a Favorskii-like cyclopropanone intermediate, is proposed. 

The molecular mechanisms for the ring openings of various cyclopropanone systems in the gas phase have been studied at the PM3 semiempirical level and shown to be disrotatory processes, while an experimental study of the stereomutation of 1,1-difluoro-2-ethyl-3-methylcyclopropane has confirmed the predicted preference for disrotatory ring opening and ring closure for this system. 

The fact that C-l and C-2 were found to be equally labeled showed that both migrations occurred, with equal probability. Since C-2 and C-6 of 52 are not equivalent, this means that there must be a symmetrical intermediate.150 The type of intermediate that best fits the circumstances is a cyclopropanone,151 and the mechanism (for the general case) is formulated (replacing R1 of our former symbolism with CHR5R6, since it is obvious that for this mechanism an a hydrogen is required on the nonhalogenated side of the carbonyl) ... 

The quasi-Favorskii rearrangement obviously cannot take place by the cyclopropanone mechanism. The mechanism that is generally accepted (called the semibenzilic mechanisml57)... 

When getw-dibromocyclopropanes are heated with alcoholic potash, cyclopropanone acetals and propargylic ethers are obtained.42 The mechanism was discussed. 

The formation of exs-di-Z-butylcyclopropanone (250) from the acyclic precursor (248) on treatment with Cr(CO)4NO has provided evidence both for the existence of oxyallyl intermediates (249) in the mechanism of this reaction and for the integrity with which oxyallyls ring close to cyclopropanones by a disrotatory route.291... 

A cyclopropanone thioacetal has also been observed to undergo Ci—C2 cleavage under the normal conditions for thioacetal solvolyses.110> Thus, the esters 135 a and 135 b are formed when the 1,3-dithiopropane ketal of 7,7-norcarane is reacted with mercuric chloride. In this case, HgCl+ acts as an electrophile and attacks the three-membered ring. However, under similar conditions, the cyclopropanone methyl thioketal 136 forms the mixed ketal 137. While the authors consider this result to represent an unusual example of a nucleophilic displacement at a cyclopropyl carbon atom 110), the reaction mechanism may involve the inter-... 

Perhaps more informative are the data in Table 22 for the relative rates of reaction of various cyclopropanones with furan. The results are consistent with the mechanism given in Scheme 32 where k >kz [furan], although the kinetic data do not distinguish between the closed cyclopropanone form and the zwitterionic intermediate. Increasing substitution would, of course, increase the stability of the allyl cation. 

A very plausible mechanism for this would involve loss of hydrogen chloride from XXII to form the bicyclohexanone (XXXII) this is a cyclopropanone derivation and would certainly react at once with alkali to give XXXI. The problem is to explain how this comes about. One possibility might be a-elimination of HC1 from XXX to form a carbene but this seems unlikely such a carbene would in any case be expected to rearrange to cyclohexenone rather than to XXXII. Another possibility would be an internal displacement of chloride ion from the conjugate base of XXX, as indicated in XXXIII this, however, is sterically improbable since in the grouping —CH2—CH=-CO—CHC1— the... 

Wiseman JS, Nichols JS, Kolpak MX (1982) Mechanism of inhibition of horseradish peroxidase by cyclopropanone hydrate. J Biol Chem 257 6328-6332... 

Other chemists prefer a pericyclic description of the ring-closure step. The same enolate simply loses chloride to give an oxyallyl cation —a dipolar species with an oxyanion and a delocalized allylic cation. This species can cyclize in a two-electron disrotatory electrocyclic reaction (Chapter 36) to give the same cyclopropanone. We shall return to this discussion in the next chapter but, whatever the mechanism, there is no doubt that a cyclopropan one is an intermediate. 

The generally accepted mechanism for the Favorskii rearrangement involves the formation of reactive cyclopropanone intermediate C. Base abstracts the a-hydrogen from A to give the carbanion B, which undergoes intramolecular Sn2 displacement of the halide ion. The resulting cyclopropanone intermediate C is opened under the reaction conditions to give the more stable carbanion D, which takes proton from solvent to furnish the final product, an ester E (Scheme 2.25). 

These mechanisms were finally discounted by Loftfield [3047, who used the isotopically labelled compound 15) and showed that only half of the label appeared at the carboxyl-bearing carbon in the product. A mechanism involving the reactive cyclopropanone intermediate (16) accounts for the isotopic distribution, and has gained general acceptance... 

This mechanism for cyclopropanone cleavage is supported by recent deuterium-incorporation, experiments [2gg]. The reaction in CH3OD/ D2O as solvent gave products with only one deuterium atom in the methyl group, consistent with the addition of D+ during the final step. 

Translation of these results into compound I leads to structure X. Unraveling of the strained zwitterion XI derived from this would yield keto aldehyde XII, a structure that plays a central role in the various possible reaction mechanisms that branch off from the starting material I. Furthermore, under photo-lytic conditions, some alkenes react with carbonyl compounds to form four-membered cyclic ethers, namely, oxetanes, by way of a [2-1-2] cycloaddition reaction known as the Patemo-Buchi process. Such a reaction would be all that is necessary to convert XII into the bicyclic cyclopropanone XIII required for the Favorskii-type rearrangement (see Scheme 42.3). Splitting by methanol attack would directly yield compound II. 

The substitution pattern of the cyclopentenones requires the loss of the oxo group rather than of the carbonyl of the carboxyl group. The mechanism is believed to consist of the formation of an acylketene with subsequent thermally allowed tc 2s -f tc 2a electrocyclic reaction leading to an intermediate cyclopropanone which then undergoes carbon monoxide elimination ... 

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