Cyclopropylmethyl chloride

The reaction of [H2C(SiMe3)2C]2Si 180 with cyclopropylmethyl chloride proceeds via ring opening and formation of product 192 containing a spirocyclic Si atom, whose formation can be attributed to a radical-reaction pathway... 

V-(3-Decyloxy-4-hydroxyphenyl)aminomethylenemalonate (1488, R = H) was treated with sodium hydroxide in toluene and was then reacted with cyclopropylmethyl chloride in the presence of a catalytic amount of sodium iodide in DMF at I20-I25°C for 2 hr to give the 3-decyloxy-4-cyclopropylmethoxyphenyl derivative (1488, R = cPrCHzO) (74GEP-2431584, 74NEP8800). 

In 1951 Roberts and Mazur observed that the free radical chlorination of methylcyclopropane gave a mixture of cyclopropylmethyl chloride and 4-chloro-l-butene (equation 74). This reaction was studied furtherand in 1969 Kochi, Krusic, and Eaton observed the cyclopropylmethyl radical 46 by ESR and also monitored its rearrangement. 

The cyclopropyl halides are exceptional in that their behavior is much more like alkenyl halides than like secondary alkyl halides. Thus cyclopropyl chloride undergoes SN1 and SN2 reactions much less rapidly than isopropyl or cyclohexyl chlorides. A relationship between the reactivity of cyclopropyl chloride and chloroethene is not surprising in view of the general similarity between cyclopropane rings and double bonds (Section 12-5). This similarity extends to cyclopropylmethyl derivatives as well. Cyclopropylmethyl chloride is reactive in both SN-1 and SN2 reactions in much the same way as 3-chloropropene ... 

SYNTHESIS To a solution of 2.8 g homosyringonitrile (see under E for synthesis) in 20 ml acetone containing about 50 mg decyltriethylammonium iodide, there was added 3.0 g cyclopropylmethyl chloride and 5.0 g Nal. Stirring was continued during a color change from pale yellow to blue. There was then added 2.9 g of finely... 

The cyclopropylmethyl cation has recently been generated in the gas phase from both homoallyl chloride and cyclopropylmethyl chloride and studied using collisional activated dissociation mass spectrometry.216 Interestingly, cyclobutyl chloride, which yields the cyclopropylmethyl cation in the condensed phase, gives a substantial amount of the bicyclobutonium ion in the gas phase. 

C H7 ions were generated by collisionally activated dissociation (CAD) in the gas phase from various precursors.216Mass spectrometric analysis showed thathomoallyl chloride and cyclopropylmethyl chloride generated primarily cation 521, whereas cyclobutyl chloride gave a substantial amount of bicyclobutonium ion 522. 

The first reported synthesis of cyprodime utilized as starting material the highly potent opioid agonist 4,14/J-dimethoxy-iV-methylmorphinan-6-one (24) which is available from oxymorphone in six steps [72]. A-Demethyla-tion was achieved with the 2,2,2-trichloroethyl carbamate to give (25) which was cleaved reductively with activated zinc and ammonium chloride to afford /V-normorphinan (26). Alkylation with cyclopropylmethyl chloride provided cyprodime (23). 

One case where C—C bonds are exceptionally effective in hyperconjugation is in the stabilisation provided by a cyclopropyl substituent to an empty p orbital. The cyclopropylmethyl cation is actually better stabilised than an allyl cation, as judged by the more rapid ionisation of cyclopropylmethyl chloride 2.19 than of crotyl chloride 2.20. In this case, hyperconjugation appears, unusually, to be better than n conjugation. 

Butenyl- -chlorid XIII/2h, 95 Cyclopropylmethyl- -chlorid XIII/6,... 

The reaction of the enantiomerically enriched silyllithium compound 4 [prepared from disilane (/J)-12] with cyclopropylmethyl chloride occurs with retention of the configuration [(/ )-14], while, for cyclopropylmethyl bromide and iodide, mainly Inversion of the configuration [(S)-14] was observed. The products of the radical reaction (15) indicate a racemization at the silicon center. 

In the presence of NbCls, allyltrimethylsilane reacts with aldehydes in 2 1 stoichiometry with concomitant formation of a cyclopropane ring (Scheme 10.160) [445], It has been proposed that this reaction proceeds via cationic isomerization of a cyclopropylmethyl chloride intermediate. 

All these fairly similar results are, however, in sharp contrast to solvolysis of cyclopropylmethyl chloride, which is much more reactive than cyclobutyl chloride or 4-chlorobut-2-ene (Roberts and Mazur, 1951 a). There was also positive evidence for internal return in the cyclopropylmethyl chloride solvolysis, although the solvent used (50 aqueous ethanol) is known to be unfavorable for internal return. Another reaction, closely related to the protolysis of cyclopropyldiazomethane mentioned above, is the reaction of that diazoalkane with ethereal benzoic acid. The product ratio cyclopropylmethanol cyclobutanol = 5.8 indicated a strong decrease of skeletal rearrangement (Moss and Shulman, 1968). 

Another system, which has attracted much interest, is that of the cyclopropyl-methyl cation, for similar reasons to the 2-norbomyl systems namely, the great ease of solvolysis of cyclopropyhnethyl substrates accompanied by formation of rearrangement products. Of particular interest is that regardless of the method of generation of the cationic species the ratio of products is always very similar. Both hydrolysis of cyclopropylmethyl chloride under conditions favoring 1 substitution and diazotization of cyclopropylamine produce cyclobutanol and but-3-en-l-ol as well as cyclopropyhnethanol in approximately 47%, 5%, and 48% yields respectively. Moreover, diazotization of cyclobutylamine also produces the same three alcohols in the same ratios (Scheme 2.38). 

The driving force for participation also more than offsets the transition-state strain in the case of 2-chloromethylthiirane (24). The acetolysis of (24) proceeds 1000 times faster than cyclopropylmethyl chloride and gives, as one product, 3-acetoxythietane via the sulfonium ion (25) [Eq. (8)]. The oxygen analog of (24), epichlorohydrin, reacts 3 times as fast as cyclopropylmethyl chloride, which is already accelerated relative to primary derivatives (see Chapter 2). 

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