Bromonium Di-sym-collidine Perchlorate1

[4836-12-8]  · C16H22BrClN2O4  · Bromonium Di-sym-collidine Perchlorate  · (MW 421.72)

(reactive electrophilic brominating agent; activates alkenes towards nucleophilic reagents;2 reagent for bromocyclization,3,4 useful in the preparation of cis-a-alkylamino alcohols)

Alternate Names: bromonium dicollidine perchlorate; bis(collidine)bromonium perchlorate.

Physical Data: mp 230 °C.

Solubility: sol chloroform; insol ether.

Form Supplied in: fine colorless crystalline powder.

Preparative Method: it is important in the preparation of this reagent to be sure that conditions are anhydrous, otherwise bromine tends to be reliberated. Silver di-sym-collidine perchlorate is prepared by adding sym-collidine (20 mL) to a solution of silver nitrate (9 g) and sodium perchlorate (11 g) in 100 mL of water, while stirring vigorously, to give a curdy white precipitate. After washing repeatedly with water, the product is washed with ethanol and ether and finally dried under vacuum over P2O5. The yield is quantitative. Silver di-sym-collidine perchlorate (13.47 g, 30 mmol) is suspended in 150 mL of chloroform and 1 mL of sym-collidine. Bromine (1.65 mL, 30 mmol) is added. Silver bromide rapidly precipitates and is filtered through Celite. The clear pale-yellow filtrate gives a fine, white crystalline precipitate on the addition of ether. The crystals are dried under high vacuum.

Handling, Storage, and Precautions: perchlorates are potentially powerful explosives. This compound detonates on strong heating and so due precautions1 must be taken. The compound is stored under anhydrous conditions. This reagent should be handled in a fume hood.

Preparation of Glycosides and Nonreducing Disaccharides.1

Reaction of D-glucal triacetate (2) with equimolar amounts of methanol and bromonium di-sym-collidine complex (1) dissolved in chloroform gives virtually quantitative yields of acetylated methyl 2-deoxy-2-bromoglycosides. Unlike pyridine or 2-methylpyridine, the steric hindrance to N-glycoside formation provided by the methyl groups at the 2- and 6-positions of sym-collidine is required for successful O-glycoside synthesis. If 2,3,4,6-tetra-O-acetyl-b-D-glucose (3) is used as the alcohol, the 2-deoxy-2-bromo disaccharide heptaacetate (4) is formed (eq 1). Deacetylation with Triethylamine in aqueous methanol followed by hydrogenolysis with Palladium on Carbon as the catalyst affords b-D-glucopyranosyl-2-deoxy-a-D-arabino-hexopyranoside (2-deoxyneotrehalose), isolated as the crystalline heptaacetate (5).

Bromocyclization3 of Unsaturated Thiocarbamidates.

This reagent can effect the stereo- and regiospecific functionalization of alkenes to furnish cis-1,2-methylamino alcohols in protected form. For example, unsaturated thiocarbamates, prepared as shown in eq 2, on treatment with bromonium dicollidine perchlorate cyclize to bromocarbamates. This cyclization has been successfully applied to several cyclic and acyclic unsaturated alcohols using methyl, benzyl, and t-butyl isothiocyanates. In all cases the condensation step (6 to 7) is essentially quantitative. The product (8) can be converted into cis-a-alkylamino alcohols by reduction of the bromine with Tri-n-butylstannane followed by alkaline hydrolysis. When R is a t-butyl group it can be removed in high yield by treatment with Trifluoroacetic Acid at 25 °C. The value of these transformations for the synthesis of aminocyclitols is illustrated by the conversion of bromocarbamate (9) to (±)-sporamine (10) in three steps (TFA; n-Bu3SnH; aqueous NaOH, 25 °C) in better than 90% overall yield (eq 3). Sporamine is the aminocyclitol portion of the broad-spectrum antibiotic sporacin A.

Bromolactamization.

Esoaminuroic acid (11), an amino sugar, is present in esomycin A, which is an antifungal antibiotic isolated from Streptomyces. The key step in its synthesis is the transannular bromolactamization of an unsaturated amide (eq 4).4

N-(R)-p-Methoxyphenethylamides were subjected to the bromolactamization sequence involving the use of Trimethylsilyl Trifluoromethanesulfonate as the amide silylating agent, and bromonium dicollidine perchlorate as electrophile. The desired [3.2.1] lactams were the only cyclization products, with yields exceeding 75% (eq 5). No [2.2.2] lactams were formed in detectable quantities. It may be noted that the N,O-bis(t-butyldimethylsilyl) derivative gave more [2.2.2] product, particularly at higher temperature.5


1. Lemieux, R. U.; Levine, S. CJC 1964, 42, 1473.
2. Perchlorates, their Properties, Manufacture and Uses; Schumacher, J. C., Ed.; Reinhold: New York, 1960; p 187.
3. Knapp, S.; Patel, D. V. JACS 1983, 105, 6985.
4. Knapp, S.; Levorse, A. T.; Potenza, J. A. JOC 1988, 53, 4773.
5. (a) Takaoka, K.; Kuwayama, T.; Aoki, A. Jpn. Pat. 615 332, 1971. (b) Sakata, K.; Sakurai, A.; Tamura, S. ABC 1973, 37, 697.

Tapan Ray

Sigma Radiochemical Co., St. Louis, MO, USA



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