1- Chloro-l-methylcyclopropanes

The pyrolysis of chlorodiazirines appears to parallel that of unsubstituted diazi-rines. For the 3-chloro-3-methyl, 3-chloro-3-ethyl, 3-chloro-3-isopropyl and 3-chloro-3-r-butyI derivatives the decompositions are kinetically of the first order with A factors close to 10 and energies of activation of about 31 kcal.mole . The intermediacy of carbenes is postulated by analogy with the photolysis of 3-chloro-3-methyl-diazirine in the presence of ethylene where the major product has been tentatively identified as 1-chloro-l-methylcyclopropane. 

FIGURE 2. Potential energy diagram (MNDO) for isomerization and dissociation of ionized 1-chloro-l-methylcyclopropane (33)... 

The preparation of l-chloro-1,2,2-trimethylcyclopropane with butyllithium, and a mixture of c/.9/ ra . -l-ehloro-l-methyl-2-vinylcyclopropanes with sodium hexamethyldisilazanide is described in Houben-Weyl, Vol. E19b, p 1515. Examples of 1-chloro-l-methylcyclopropanes are collected in Houben-Weyl, Vol. E19b, pp 1515-1516, and in Table4. 

Table 4. 1-Chloro-l-methylcyclopropanes from 1,1-Dichloroethane, Butyllithium or Sodium Hexa-methyldisilazanide and Alkenes...

Due to a growing interest in poly-spirocyclopropanes (triangulanes), a general approach to their synthesis has been developed. It consists of the addition of chlorofmethyl)-carbene to an alkene, the dehydrochlorination of the product 1-chloro-l-methylcyclopropane to a methylenecyclopropane, which is then submitted to cyclopropanation. The chloro(methyl)spiroalkanes 2 have been prepared utilizing this approach. 

Reaction of 1,1,1-trichloroethane with reducing agents and alkenes has rarely been used for the preparation of 1-chloro-l-methylcyclopropanes 34 and 35. °... 

In hindered or strained systems the yields are more variable. Thus, the yield of methylene product from 1-chloro-l-methyl-2,2-diphenylcyclopropane was only 39%. ° In a series of methylenecyclopropanes containing a bicyclic system with aryl bridgehead substituents, the yields in some cases were very poor (Table 1). In the absence of such substituents, however, the yields are generally very good. Thus, a 78% yield of pure 7-methylenebicyclo[4.1.0]heptane (13, n = 2) and a 85% yield of pure c/5-9-methylenebicyclo[6.1.0]nonane (13, n = 6) were obtained from the 1-chloro-l-methylcyclopropanes 12 derived from cyclohexene and (Z)-cyclo-octene, respectively. ... 

It is also possible to obtain methylenecydopropanes by monodehydrochlorination of compounds other than 1-chloro-l-methylcyclopropanes. For example, inverse addition of potassium terf-butoxide in dimethyl sulfoxide at 25°C to l,l-dichloro-2,2,3-trimethylcyclopropane (20) gave a 33% yield of 2-chloro-l,l-dimethyl-3-methylenecyclopropane (21) along with a 30% yield of ring-opened product 22. This is one case in which the usual double dehydrochlorination of 1,1-dichlorocyclopropanes (see Section 5.2.2.1.2.3.) is blocked and a single elimination occurs instead. Another example is the reaction of l-chloro-2,3-dimethylcyclopropane (23) with potassium tcr/-butoxide in dimethyl sulfoxide at 80-90 to give l-methyl-2-methyl-enecyclopropane (24) in 84% yield (see also below and Sections 5.2.2.1.1.1.2. and 5.2.2.1.1.2.). 

Table 1. Methylenecydopropanes by Dehydrochlorination of 1-Chloro-l-methylcyclopropanes with Potassium te Butoxide in Dimethyl Sulfoxide...

The most successful method for preparing ring-alkylatcd and -arylated methylene cyclopropanes is dehydrochlorination of 1-chloro-l-methylcyclopropanes. These are in turn readily accessible from the combination of substituted alkenes and 1,1-dichloroethane in the presence of a suitable base35. 

Methylenecyclopropanes. Arora and Binger have used both sodium bis(tri-methylsilyl)amide and n-butyllithium in ether to generate chloromethylcarbene from 1,1-dichloroethane. The carbe.ie reacts with alkenes to form 1-chloro-l-methylcyclopropanes in 40-80% yields. These products are converted into methylenecyclopropanes in 60-100% yield by potassium r-butoxide in DMSO. 

When two equivalents of methanethiol were added to the reaction mixture, 12% of the rm-butyl ether along with 34% of l-methylene-2-(methylsulfanyl)cyclopropane(3) were obtained. - Product 3 could be obtained in 51% yield by using 4 equivalents of methanethiol. Reaction of 2-bromo-l-chloro-l-methylcyclopropane (1, X = Br) with potassium tert-butoxide in tetrahydrofuran, and with potassium tert-butoxide plus methanethiol in dimethyl sulfoxide, likewise gave the tert-butyl and sulfanylmethyl ethers in 30 and 47% yield, respectively. 

The increased strain in methylenecyclopropane, which is relieved on ring opening, makes the cyclic bonds more liable to cleavage than methylcyclopropane. Photochlorination of methylenecyclopropane (3) in the liquid phase produced a mixture of several addition products including 3-chloro-2-chloromethylprop-2-ene (42%), 2,4-dichlorobut-l-ene (27%), 1-chloro-l-chloromethylcyclopropane (18 /o), 1,2,3,4-tetrachlorobutane (11 %), and 1,3-dichloro-2-chloro-methylprop-l-ene (2%). ... 

Cyclopropancs. A soln. of n-butyllithium in hexane added slowly at -105° during 45 min. to a soln. of benzotrichloride in tetrahydrofuran, then tetra-methylethylene added, the resulting slurry allowed to warm slowly whereupon at ca. -65° complete exothermic dissolution occurs 1-chloro-l-phenyltetra-methylcyclopropane. Y 72%. F. e. and reactions s. D. F. Hoeg, D. I. Lusk, and A. L. Grumbliss, Am. Soc. 87, 4147 (1965) O. Kobrich and W. Drischel, Tetrahedron 22, 2621 (1966). 

The reaction of either cis- or trans-1 with potassium /-butoxide in tetrahydrofuran at 25 °C leads to a /-butyl ether (2), apparently arising by attack of /-butoxide ion on an intermediate l,4-di-/-butylmethylenecyclopropene. If the reaction is carried out at low temperature and the volatile materials are distilled directly into a cold trap, the cyclopropene can be trapped, albeit in low yield (10 %), by added cyclopentadiene or detected directly by low-temperature NMR23. In a related example, a l,l-dihalo-2-bromo-3-methylcyclopropane (2a) leads to products which are also apparently derived through an intermediate 1 -chloro-3-methylenecyclopropene which undergoes nucleophilic addition (See Ref. 80). 

S)-1 -Chloro-Chromatography column, water-jacketed, 37... 

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. 

Photochlorination of cyclopropane gave chlorocyclopropane (la) and 1,3-dichloro-propane. The latter was the major product at low temperature. Photochlorination with tert-h Ay hypochlorite gave mostly chlorocyclopropane (la). Methylcyclopropane reacted with chlorine to give predominantly l-chloro-2-methylcyclopropane (lb), but small amounts of acyclic products such as 2-chlorobutane, 1,3-dichlorobutane, and 1,3-dichloro-2-methyl-propane were also obtained. With ferr-butyl hypochlorite 4-chlorobut-l-ene was isolated as the only acyclic product. Photochlorination of 1,1-dimethylcyclopropane in trichloro-fluoromethane atO°C gave the chloromethylcyclopropane derivative 2 in 67% yield after immediate workup. 

Azatricyclo[2.2.1.02 6]hept-7-yl perchlorate, 2368 f Azetidine, 1255 Benzvalene, 2289 Bicyclo[2.1.0]pent-2-ene, 1856 2-/ert-Butyl-3-phenyloxaziridine, 3406 3 -Chloro-1,3 -diphenyleyclopropene, 3679 l-Chloro-2,3-di(2-thienyl)cyclopropenium perchlorate, 3388 Cyanocyclopropane, 1463 f Cyclopropane, 1197 f Cyclopropyl methyl ether, 1608 2,3 5,6-Dibenzobicyclo[3.3.0]hexane, 3633 3,5 -Dibromo-7-bromomethy lene-7,7a-dihy dro-1,1 -dimethyl-1H-azirino[l,2-a]indole, 3474 2.2 -Di-tert-butyl-3.3 -bioxaziridinc, 3359 Dicyclopropyldiazomethane, 2824 l,4-Dihydrodicyclopropa[ >, g]naphthalene, 3452 iV-Dimethylethyl-3,3-dinitroazetidine, 2848 Dinitrogen pentaoxide, Strained ring heterocycles, 4748 f 1,2-Epoxybutane, 1609 f Ethyl cyclopropanecarboxylate, 2437 2,2 -(l,2-Ethylenebis)3-phenyloxaziridine, 3707 f Methylcyclopropane, 1581 f Methyl cyclopropanecarboxylate, 1917 f Oxetane, 1222... 

When no other nucleophile is added, only one mol of tert-butoxide adds to the substrate. Thus, reaction of 2-(bromomethyl)-l, 1 -dichlorocyclopropane (27) with potassium tert-butoxide in tcr/-butyl alcohol gives a 49yo yield of /ra 5-l-tert-butoxy-2-chloro-3-methylenecyclo-propane (28), along with 9% of ring-opened product 29. The same methylenecyclopropyl ether 28 was obtained from the reaction of 2-bromo-l,l-dichloro-3-methylcyclopropane (30) with potassium tert-butoxide. 

A mixture of DMSO (5 mL), powdered NaOH (1.2 g, 30 mmol), TEBAC (0.5 g, 0.22 mmol), and ben-zenethiol (0.66 g, 6 mmol) was stirred until the thermal effect ceased. A solution of l-bromo-2-chloro-methylcyclopropane (0.85 g, 5 mmol) in DMSO (5 mL) was then added, and the reaction was heated at 56-58 C for 2 h. The mixture was poured into HjO and extracted with CHClj or CH2CI2 (3 x 100 mL). The combined extracts were washed with HjO, dried (MgS04), and concentrated on a rotary evaporator. The residue was subjected to vacuum distillation yield 0.75 g (62%) bp 105°C/0.05 Torr. 

Thiocyanate ion can cause isomerization of thiirans. The reactivity of 2-methylthiiran to hydrochloric acid has been compared with the reactivities of 2-methyloxiran, 2-methylaziridine, and methylcyclopropane. Treatment of 2-chloromethyl- and 2-alkoxymethyl-thiirans with aqueous chlorine yields the corresponding 1,3-dichloropropane- or l-alkoxy-3-chloro-2-sulphonyl chlorides. Hydrochloric acid alone yields the 2-thiol. Nucleophilic attack on the sulphur atom of 2-bromomethylthiiran by potassium thiobutoxide yields the disulphide (60). Attack by the sulphur atom of 2-methylthiiran on benzoyl isocyanate (61) yields a mixture believed to contain (62). ... 

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