Commonly used protective base reagents - p-Bromobenzyl bromide

[English name] p-Bromobenzyl Bromide


[Molecular Formula] C7H6Br2


[molecular mass] 249.94


[CAS No.] 589-15-1


Abbreviations and aliases]: PBB, α-Bromo-4-Bromotoluene


Physical Properties]: Light yellow crystals, 60-62 °C, bp 116-124 °C/12 Torr (1599.86 Pa). Soluble in hot alcohols, ethers, carbon disulfide, benzene and glacial acetic acid, soluble in water and alcohol. It can be volatilized with water vapor and sublimated when heated.


【Preparation and commodities】It is sold by domestic and foreign reagent companies. It can also be prepared by bromination of 4-bromotoluene under light [1], or 4-bromotoluene by NBS catalyzed by benzoyl peroxide [2].


[Precautions] Sensitive to moisture, need to be stored under nitrogen protection. Lachrymatory corrosive, irritating to eyes, respiratory system, skin.


Benzyl bromide p-bromide (BPP) is one of the important alkylating reagents in the laboratory. It can be used in alkylation reactions of N-, O- and C-atoms under appropriate conditions. Under alkaline conditions, this reagent can be alkylated with primary or secondary amines to give N-bromobenzyl compounds (formula 1) [3]. In the presence of potassium carbonate, p-bromobenzyl bromide can be selectively reacted with the amine group of a diolamine to give N-p-bromobenzyl diethanolamine (formula 2) [4].






In the presence of sodium hydride, the reagent can undergo Williamson reaction with alcohols, phenols and sulfur ethers to give the corresponding p-bromobenzyl ethers. Since p-bromobenzyl ethers can be stabilized under alkaline, acidic and oxidizing conditions and at the same time can be removed under appropriate conditions, they are often used as protecting groups (Eq. 3) [5].


In addition, differences in the dissociation ability of different p-benzyl halogenated ethers can be utilized to achieve selective removal of the protecting group [5,6]. When para-halogenated benzyl ethers containing iodine, bromine or chlorine are present simultaneously, the former can be preferentially removed (Eq. 4).


Alkylation of this reagent with active methylene or hypomethyl groups can be carried out at different bases and lithium bis(trimethylsilyl)amide, LDA, potassium alcohol and potassium carbonate are often used for this purpose (Eq. 5) [7].


Palladium chloride catalyzed Suzuki coupling reaction of p-bromobenzyl bromide with arylboronic acids selectively occurs on aryl bromides [8]. When Pd(PPh3)4 was used as a catalyst, the reaction then occurred selectively on benzyl bromide. When an excess of arylboronic acid is used, the coupling reaction (Eq. 6) can occur simultaneously at both sites [9].


In the presence of Fe(II) catalyst, this reagent can undergo Negishi coupling reaction with aryl zinc reagent (Eq. 7) [10].


Catalyzed by an indium metal reagent, the reagent can react with diselenide compounds to give monoselenide compounds (Eq. 8) [11]. In the presence of NaH, the reagent can react with trichloromethane in a substitution reaction to give 1-(2,2,2-trichloroethyl)-4-bromobenzene (formula 9) [12]. In the presence of a base, the reagent reacts with disodium iron pentacarbonyl or tetracarbonylferrate to give bis(p-bromobenzyl ketone) (formula 10) in higher yield [13]. The reagent was oxidized to p-bromobenzoic acid (Eq. 11) in 71% to 89% yield under NalO4/H+ conditions.


References.


1. Weizmann, M.; Patai, S. J. Am. Chem. Soc. 1946, 68,150.


2. Gassman, P. G.; Macomber, D. W.; Willging, S. M. J. Am. Chem. Soc. 1985,107,2380.


3. Wan, Y.; Wallinder, C.; Plouffe, B.; Beaudry, H. J. Med Chem. 2004, 47, 5995.


4. Aranapakam, V.; Davis, J. M.; Grosu, G. T. J. Med Chem. 2003, 46, 2376.


5. Plante, O. J.; Buchwald, S. L.; Seeberger, P. H. J. Am. Chem. Soc. 2000,122,7148.


6. Wolfe, J. P.; Tomori, H.; Yin, J.; Sadighi, J.; Buchwald, S. L. J. Org. Chem. 2000, 65,1158.


7. Gonzalez-Cantalapiedra, E.; Ruiz, M.; Gomez-Lor, B.; Alonso, B.; Garcia-Cuadrado, D.; Cardenas, D.J.; Echavarren, A. M. Eur. J. Org. Chem. 2005, 4127. 4127.


8. Bandgar, B. P.; Bettigeri, S. V.; Phopase, J. Tetrahedron Lett. 2004, 45,6959.


9. Langle, S.; Abarbri, M.; Duchene, A. Tetrahedron Lett. 2003, 44, 9255.


10. Bedford, R. B.; Huwe, M.; Wilkinson, M. C. Chem. Commun. 2009,600.


11. Lee, E. H.; Kim, S. J.; Singh, G.; Jang, D. O.; Munbunjong, W.; Ngemmaneerat, P.; Chavasiri, W. Tetrahedron 2009, 55,2467.


12. Baati, R.; Barma, D. K.; Krishna, U. Murali; Mioskowski, C.; Falck, J. R. Tetrahedron Lett. 2002, 43,959.


13. (a) Ito, S.; Wehmeier, M.; Brand, J. D.; Kuebel, C.; Epsch, R.; Rabe, J. P.; Muellen, K. Chem. Eur. J. 2000, 6,4327. (b) Potter, R. G.; Hughes, T. S. J. Org. Chem. 2008, 75,2995.