Cyclopropyl chloride, reaction

Cyclopropyl chloride has been prepared by the free-radical chlorination of cyclopropane. Write a stepwise mechanism for this reaction. 

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 ... 

The amphetamine analog of CPM should be easily made from the alkylation of syringaldehyde with cyclopropyl chloride, followed by conventional reaction of the resulting aldehyde with nitroethane, and finally a reduction step. There is no reason to believe that the resulting compound 3,5-dimethoxy-4-cyclo-propyloxyamphetamine (3C-CPM) would be any shorter acting than CPM. 

Cleavage of a cyclopropyl ketone. Reaction of 1 with benzeneselenenyl chloride at room temperature gives a mixture of 2 and 3. The latter compound was converted into ( )-erysotramidine (4) by reaction with CHjOH and AgNOs followed by desulfurization with Raney nickel (507o overall yield). 

In this 3-phcnylalkyne system the triple bond becomes incorporated into a cyclo-propene ring, whereas from the enynes 10 and 11 there is no sign of a vinylcyclo-propene product. The preference for reaction to take place at the alkene unit rather than at the alkyne unit in the photochemistry of enynes is seen again in the photochemistry of enepoly-yne chlorides, where only cyclopropyl chlorides are produced (equation 18). This preference is probably a reflection of the lower strain energy in a cyclopropane than in a cyclopropene ring. 

Many cyclopropyl chlorides and bromides have been converted to alkoxycyclopropanes by treatment with a strong base, in most cases potassium rerf-butoxide, in an appropriate organic solvent (Table 13). Under such conditions, hydrogen halide elimination takes place, yielding strained cyclopropene intermediates, which are trapped by nucleophilic attack of the alkoxide. Overall, a simple substitution occurs when a bond is formed between the alkoxide group and the carbon atom to which the halide was attached. This is the case when l-chloro-5-methyl-exo-6-phenyl-3-oxabicyclo[3.1.0]hexan-2-one (1) was reacted with potassium /ert-butoxide l-/er/-butoxy-5-methyl-ent/o-6-phenyl-3-oxabicyclo[3.1.0]hexan-2-one (2) was isolated in 94% yield.If a C-O bond is established at the other olefinic carbon atom, a C H bond is concomitantly formed at the carbon atom, to which the halide was attached. The result is a double substitution which is discussed elsewhere (see Section 5.2.1.3 ). When the substrate contains more than one halogen atom, several elimination reactions usually take place. Thus, treatment of 1 -bromo-2-chloro-2-methylcyclopropane (3) with an excess of potassium /er/-butoxide gave l-ter/-butoxy-2-methylenecyclopropane (4) in 30% yield. 

The most general entry into functionalized sulfur-containing cyclopropanes is the addition reactions of cyclopropanones and thiols (see Section 5.2.3.5.4.). Thus, reaction of cyclo-propanone with thiols in dichloromethane affords l-(alkylsulfanyl)cyclopropanols 39 which are readily transformed into the corresponding cyclopropyl bromides 40 and cyclopropyl chlorides 41 upon reaction with anhydrous hydrogen bromide and hydrogen chloride, respectively. ... 

The synthesis of the corresponding naphthyridone scaffold was carried out according to the methods reported by Chu et al. [12] and Sanchez et al. [13]. Namely, the hydrolysis of ethyl 2,6-dichloro-5-fluoronicotinate (3) [14] followed by reaction with thionyl chloride results in the formation of 2,6-dichloro-5-fluoronicotinyl chloride (4). Treatment of this compound with monoethyl malonate in THF under n-butyllithium followed by acidification and decarboxylation gives rise to ethyl 2,6-dichloro-5-fluoronicotinylacetate (5). Reaction of compound 5 with ethyl orthoformate in acetic acid followed by cyclopropylamine results in the formation of 3-cyclopropylamino-2-(2,6-dichloro-5-fluoronicotinyl)acrylate (6), the cyclization reaction of which under NaH/THF gives rise to the required ethyl l-cyclopropyl-6-fluoro-7-chloro-l,4-dihydro-4-oxo-l,8-naphthyridine-3-carboxylate (7), as shown in Scheme 3. 

The synthesis of the moxifloxacin core (de Souza, 2006 Martel et al., 1997 Seidel et al., 2000) proceeds from a Grohe-Heitzer sequence as described earlier in the chapter. Unlike the traditional Grohe-Heitzer sequence, however, the opening step involved the reaction between acid chloride 101 with the mono potassium salt of malonic acid monoethyl ester (102) in the presence of triethylamine to deliver ketoester 103 (Scheme 4.18). Treatment of 103 with ethyl orthoformate furnished acrylate 104, which reacted with cyclopropyl amine to afford 105. Cyclization of 105 in the presence of sodium fluoride in DMF gave the moxifloxicin core 106. 

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