Chloroiodomethane1

ClCH2I

[593-71-5]  · CH2ClI  · Chloroiodomethane  · (MW 176.38)

(chloromethylating agent for organozinc,2 -lithium,3 -phosphorus,4 and -transition metal compounds,5 and alkenes;6 can generate N,N-dimethylmethyleneiminium iodide (Eschenmoser's salt) by reaction with N,N,N,N-tetramethylmethylenediamine7)

Alternate Name: CIM.

Physical Data: bp 108-109 °C; d204 2.42 g cm-3; n20D 1.582.

Solubility: sol ethers, acetone, polyhalomethanes, and benzene.

Form Supplied in: pale yellow oil; commercially available or readily preparable via halogen exchange of dichloromethane with iodide sources.1,8

Analysis of Reagent Purity: NMR (CCl4/TMS), d (ppm) 5.00.

Handling, Storage, and Precautions: should be stored over tin or silver wire in the dark.

Cyclopropanation of Alkenes.

The Diethylzinc/chloroiodomethane (CIM) reagent system is a valuable alternative to Furukawa's version of the Simmons-Smith cyclopropanation reaction (eq 1).2,9 The formation of the (chloromethyl)zinc species seems to proceed via a radical chain mechanism, considering the accelerating effect of oxygen and the retarding effect of radically polymerizable alkenes.2 The samarium carbenoid generated from Sm(Hg) and CIM cyclopropanates allylic alcohols with high regio- and stereoselectivity via the directing effect of the hydroxyl function (eq 2).10 Generally, CIM affords better results in these carbenoid reactions than Diiodomethane.

Generation and in situ Trapping of Chloromethyllithium.

The extreme thermal instability of Chloromethyllithium11 severely limits its synthetic applicability. A method has been devised to generate and trap (chloromethyl)lithium by reacting CIM with an alkyllithium in the presence of a substrate.3a,12 Addition of n-Butyllithium to a mixture of a boronic ester and CIM in THF at low temperature yields the methylene insertion product with retention of the configuration of the alkyl moiety (eq 3).3 Aldehydes and ketones can also capture the in situ generated carbanion species in THF at -78 °C.12 The initial chloromethyl adducts are amenable to further reactions depending on the substrates and reaction conditions applied,12,13 e.g. delayed hydrolytic workup yields the epoxides (eq 4).12 The chlorohydrin products can be lithiated in situ to the b-oxidoalkyllithiums for further transformations (e.g. eq 5).14

Wittig Chloromethylenation.

Treatment of Triphenylphosphine with CIM in THF at reflux forms the phosphonium iodide (1) in good yield, which in turn is transformed to the corresponding ylide by treatment with Potassium t-Butoxide and hence can chloromethylenate aldehydes and ketones (eq 6).4,15

The Mannich Reaction.

The dimethylaminomethylation of carbonyl compounds is conveniently carried out via the enol trimethylsilyl ethers by a combination of CIM and N,N,N,N-tetramethylmethylenediamine (TMMD; Bis(dimethylamino)methane) in DMSO at ambient temperature (eq 7).7 The reagent system CIM/TMMD also provides a convenient route to Eschenmoser's salt (2) (Dimethyl(methylene)ammonium Iodide) (eq 8).7

Related Reagents.

Chloroiodomethane-Zinc/Copper Couple.


1. Hahn, R. C. JOC 1988, 53, 1331.
2. (a) Miyano, S.; Hashimoto, H. BCJ 1973, 46, 892. (b) Miyano, S.; Izumi, Y.; Fujii, H.; Hashimoto, H. S 1977, 700. (c) Miyano, S.; Hashimoto, H. BCJ 1973, 46, 1895.
3. (a) Sadhu, K. M.; Matteson, D. S. OM 1985, 4, 1687. (b) Brown, H. C.; Singh, S. M.; Rangaishenvi, M. V. JOC 1986, 51, 3150. (c) Brown, H. C.; Phadke, A. S.; Rangaishenvi, M. V. JACS 1988, 110, 6263.
4. Miyano, S.; Izumi, Y.; Fujii, K.; Ohno, Y.; Hashimoto, H. BCJ 1979, 52, 1197.
5. (a) King, R. B.; Braitsch, D. M. JOM 1973, 54, 9. (b) Engelter, C.; Moss, J. R.; Nassimbeni, L. R.; Niven, M. L.; Reid, G.; Spiers, J. C. JOM, 1986, 315, 255. (c) Werner, H.; Schippel, O.; Wolf, J.; Schulz, M. JOM, 1991, 417, 149.
6. Miyano, S.; Hokari, H.; Umeda, Y.; Hashimoto, H. BCJ 1980, 53, 770.
7. Miyano, S.; Hokari, H.; Hashimoto, H. BCJ 1982, 55, 534.
8. (a) Miyano, S.; Hashimoto, H.; BCJ 1971, 44, 2864. (b) Landini, D.; Rolla, F. CI(L) 1974, 533. (c) Altabev, N.; Smith, R. D.; Suratwala, N. S. I. CI(L) 1973, 331.
9. (a) Denmark, S. E.; Edwards, J. P. JOC 1991, 56, 6974. (b) Denmark, S. E.; Edwards, J. P.; Wilson, S. R. JACS 1992, 114, 2592.
10. Molander, G. A.; Harring, L. S. JOC 1989, 54, 3525.
11. Tarhouni, R.; Kirschleger, B.; Rambaud, M.; Villieras, J. TL 1984, 25, 835.
12. Sadhu, K. M.; Matteson, D. S. TL 1986, 27, 795.
13. (a) Barluenga, J.; Llavona, L.; Concellón, J. M.; Yus, M. JCS(P1) 1991, 297. (b) Barluenga, J.; Fernández-Simón, J. L.; Concellón, J. M.; Yus, M. JCS(P1) 1989, 77.
14. (a) Barluenga, J.; Fernández-Simón, J. L.; Concellón, J. M.; Yus, M. JCS(P1) 1988, 3339. (b) Barluenga, J.; Fernández-Simón, J. L.; Concellón, J. M.; Yus, M. S 1987, 584.
15. Matsumoto, M.; Kuroda, K. TL 1980, 21, 4021.

Sotaro Miyano

Tohoku University, Sendai, Japan



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