Dibromomethane

CH2Br2

[74-95-3]  · CH2Br2  · Dibromomethane  · (MW 173.83)

(converts diols to cyclic methylene acetals;1 reagent with Zn and TiCl4 converts C=O to C=CH2;2,3 with Zn, cyclopropanates alkenes4)

Alternate Name: methylene bromide.

Physical Data: mp -52.7 °C;5 bp 96.95 °C;6 d204 2.4921,7 2.496 g cm-3;8 n20D 1.53559,7 1.5419.8

Solubility: sol water: 11.70 g L-1 (15 °C); 11.93 g L-1 (30 °C).9

Form Supplied in: commercially available.

Preparative Method: patents suggest manufacture from CH2Cl2 and HBr10 or NaBr.11

Handling, Storage, and Precautions: toxicity hazard greater than CH2Cl2, less than CH2I2 or most alkyl bromides. Absorbed through skin;12 mutagenic in Ames test13 but not in assay in Drosophila because it kills the flies (LC50 120 mg m-3 in air);14 not hepatotoxic in mice (CHCl3 is);15 should be handled in a fume hood with the usual protective gloves and clothing.

General Behavior toward Nucleophiles.

The reactivity of dibromomethane toward nucleophiles is generally less than that of ordinary alkyl bromides, and falls between diiodomethane and dichloromethane. For example, toward PhSNa in MeOH, rates (104 k, s-1, per C-X bond) at 0 °C are EtBr, 3.79; CH2I2, 1.19; CH2Br2 0.08; CH2Cl2, 0.0013 (extrapolated).16 Toward NaI in acetone, rates (105 k, s-1) at 50 °C are EtBr, 1700; CH2Br2, 69; CH2Cl2 0.2.17 Accordingly, nucleophilic substitutions that are unsatisfactory with CH2Cl2 may proceed at useful rates with CH2Br2, which is much cheaper than CH2I2. Monosubstitution products of CH2Br2 are usually more reactive toward nucleophiles than CH2Br2 itself, and the net result is that disubstitution generally occurs unless the substituent is sufficiently branched to provide steric hindrance. Alkoxy substituents greatly accelerate the second substitution and make it impossible to isolate any monosubstitution product.18

For substitutions where the reactivity of CH2Br2 or CH2I2 is insufficient, it should be possible to use methylene ditosylate or methylene chlorotosylate,18 though the reactions of these promising new reagents have not been extensively studied yet.

Methylene Acetals.

Dibromomethane is particularly useful for making methylene acetals because the reaction is irreversible. Thus not only the usual cis-fused acetals but also the less stable trans-fused acetals can be made from carbohydrates (eq 1).1 The basic phase transfer conditions are mild and compatible with much other functionality.

Similar reactions have been carried out with DMSO as solvent (eq 2).19

Analogous reactions with an alkyltrimethylammonium phase transfer catalyst provide methylene acetals of catechols (eq 3)20 and monothioacetals of mercaptophenols (eq 4).21

Reaction of phenol (PhOH) with CH2Br2, aqueous base, and a phase transfer catalyst (Bu4N+X-) yields the methylene acetal CH2(OPh)2 (90%).22 Benzoic acid with NaOH and CH2Br2 in HMPA yields CH2(O2CPh)2 (86%).23

Bromomethylation of Carbanions.

Enolates often provide sufficient steric hindrance to allow bromomethylation rather than disubstitution of CH2Br2. Recent and typical examples include a cyclobutanecarboxylic ester (eq 5)24 and a tetralonecarboxylic ester (eq 6).25

Bromomethylation of a chiral lithiated heterocycle provides intermediates useful in the asymmetric synthesis of unusual amino acids (eq 7).26 Diastereomeric excesses were 84-95%.

Cross coupling of ArMgBr with CH2Br2 in the presence of Copper(I) Bromide has yielded ArCH2Ar (60-90%).27

Methylenation of Carbonyls.

A remarkably mild and effective reagent for converting C=O to C=CH2 is obtained by reaction of dibromomethane with Zn and TiCl4 in THF (see Dibromomethane-Zinc-Titanium(IV) Chloride).2 Steric factors are minimal, and camphor was converted to the methylene derivative (92%).2 The reagent is particularly useful because it does not enolize ketones, and for example reacted with a gibberellin-related intermediate to produce the methylene derivative (eq 8) where the normal Wittig reagent yielded mainly epimerized product.28

An Organic Syntheses procedure for the use of the CH2Br2-Zn-TiCl4 reagent with (+)-isomenthone (eq 9) has been published.3 It has been found best to add the TiCl4 to the zinc and CH2Br2 in THF at -40 °C, then stir 3 days at 5 °C before use.

Other examples that illustrate the utility of this reagent include methylene-substituted nucleosides (eq 10)29 and an intermediate for chiral synthesis derived from glucose (eq 11).30

A related reagent from CH2Br2, Zn, and Dichlorobis(cyclopentadienyl)zirconium has been reported, though at the present stage of development it does not give as high yields.31

An earlier alternative for the methylenation of ketones was methylenebis(magnesium bromide), CH2(MgBr)2, or the corresponding iodide.32 However, this reagent is difficult to prepare, requiring magnesium amalgam, and offers no advantage. It does have some use in the preparation of other methylenedimetallic compounds.33

Cyclopropanations.

Dibromomethane can be used in place of Diiodomethane in the Simmons-Smith cyclopropanation process. (Bromomethyl)zinc bromide is presumably the active intermediate. In order to obtain satisfactory yields, a number of processes for activating the zinc metal have been tested. The best activator in addition to Copper(I) Chloride now appears to be a small amount of Acetyl Chloride, and previous methods have been declared obsolete.4 Typical results are illustrated in eqs 12 and 13.

Previously tested methods of activating the zinc included ultrasound34 and Titanium(IV) Chloride.35 Electrolytic activation using a zinc anode has also proved successful,36 though it appears to offer no significant advantage over less cumbersome methods.

Bromocarbene can be generated by treatment of CH2Br2 with Sodium Hexamethyldisilazide, and converts alkenes to bromocyclopropanes in yields ~40%.37 Bromochlorocarbene has been generated by treatment of CH2Br2 with PhCCl3 and 60% aqueous KOH in the presence of the phase transfer catalyst Bu4N+, and converts alkenes in situ to bromochlorocyclopropanes (45-75%).38

Related Reagents.

Bromomethyllithium; Chloroiodomethane; Dibromomethane-Zinc-Titanium(IV) Chloride; Dibromomethyllithium; Diiodomethane; Iodomethylzinc Iodide.


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Donald S. Matteson

Washington State University, Pullman, WA, USA



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