Categories: C-Br Bond Formation >
Synthesis of alkyl bromides
Substoichiometric amounts of thiourea additives mediate the halogenation of alcohols under mild conditions. In the the absence of thiourea, oxidation of the alcohol is observed, whereas the substrate can be recovered when excess thiourea is used. Both bromination and chlorination were highly efficient for primary, secondary, tertiary, and benzyl alcohols and tolerate a broad range of functional groups.
A. R. Mohite, R. S. Phatake, P. Dubey, M. Agbaria, A. I. Shames, N. G. Lemcoff, O. Reany, J. Org. Chem., 2020, 85, 12901-12911.
The use of a tetraethylammonium halide in the presences of [Et2NSF2]BF4 (XtalFluor-E) enables efficient chlorination and bromination reactions of a wide range of alcohols. Iodination reactions are also possible albeit in lower yields. As opposed to Appel reactions, water-soluble side products are generated, that facilitate work-up.
M.-F. Pouliot, O. Mahé, J.-D. Hamel, J. Desroches, J.-F. Paquin, Org. Lett., 2012, 14, 5428-5431.
Alcohols were efficiently converted to alkyl halides using 1-n-butyl-3-methylylimidazolium halide ioniq liquids in the presence of Brønsted acids at room temperature. The alkyl halide products were easily isolated from the reaction mixture via simple decantation or extraction.
R. X. Ren, J. X. Wu, Org. Lett., 2001, 3, 3727-3728.
Ionic liquids [bmim][X] (X = Cl, Br, I, OAc, SCN) are highly efficient reagents for nucleophilic substitution reactions of sulfonate esters derived from primary and secondary alcohols. The newly developed protocol is very environmentally attractive because the reactions use stoichiometric amounts of ionic liquids as sole reagents without additional solvents and activating reagents. Moreover, these ionic liquids can be readily recycled.
Y. Liu, Y. Xu, S. H. Jung, J. Chae, Synlett, 2012, 23, 2663-2666.
Nucleophilic fluorination using CsF or alkali metal fluorides was completed in short reaction time in the presence of [bmim][BF4] affording the desired products without any byproducts. Facile nucleophilic substitutions such as halogenations, acetoxylation, nitrilation, and alkoxylations in the presence of ionic liquids provided the desired products in good yields.
D. W. Kim, C. E. Song, D. Y. Chi, J. Org. Chem., 2003, 68, 4281-4285.
Silicaphosphine (Silphos), [P(Cl)3−n(SiO2)n] is a new heterogeneous reagent that converts alcohols and thiols to their corresponding bromides and iodides in the presence of molecular halogen in refluxing CH3CN in high to quantitative yields. Separation of the Silphos oxide byproduct can be achieved by a simple filtration.
N. Iranpoor, H. Firouzabadi, A. Jamalian, F. Kazemi, Tetrahedron, 2005, 61, 5699-5704.
The combination of Ph3P and easily available 1,2-dihaloethanes (XCH2CH2X; X = Cl, Br, or I), was very effective for a mild deoxygenative halogenation of alcohols and aldehydes. The use of (EtO)3P instead of Ph3P enables a convenient purification process, as the byproduct (EtO)3P═O could be removed by aqueous washing. A dehydroxy-fluorination proceeds well in the presence of ICH2CH2I and CsF as fluoride source in DMF.
J. Chen, J.-H. Lin, J.-C. Xiao, Org. Lett., 2018, 20, 3061-3064.
Treatment of primary, secondary, or tertiary alkyl fluorides with a catalytic amount of titanocene dihalides, trialkyl aluminum, and polyhalomethanes as the halogen source achieves a halogen exchange reaction in excellent yields under mild conditions. In the case of a fluorine/iodine exchange, no titanocene catalyst is needed. Only C-F bonds are activated under these conditions, whereas alkyl chlorides, bromides, and iodides remained intact.
Y. Mizukami, Z. Song, T. Takahashi, Org. Lett., 2015, 17, 5942-5945.
In a triphasic phase-vanishing system comprised of an alkane, perfluorohexanes, and bromine, photoirradiation efficiently generate hydrogen bromide, which underwent radical addition with 1-alkenes in the hydrocarbon layer to afford terminal bromides in high yields.
H. Matsubara, M. Tsukida, D. Ishihara, K. Kuniyoshi, I. Ryu, Synlett, 2010, 2014-2018.
The combination of 1,1,3,3-tetramethyldisiloxane (TMDS) and trimethylbromosilane (Me3SiBr) enabled a direct bromination of carboxylic acids in the presence of indium bromide (InBr3) as catalyst. The reducing system was tolerant to several functional groups and produced the corresponding alkyl bromides in very good yields.
T. Moriya, S. Yoneda, K. Kawana, R. Ikeda, T. Konakahara, N. Sakai, Org. Lett., 2012, 14, 4842-4845.
Under very mild oxidative conditions, 1,4-dihydropyridines (DHPs), derived from aldehydes, generate C(sp3)-radicals that couple with halogen radicals, which are generated from inexpensive halogen sources (NaBr, NaI, or HCl), to yield alkyl halides. The reaction tolerates a broad range of functional groups and achieves excellent site selectivity.
S. Liang, T. Kumon, R. A. Angnes, M. Sanchez, B. Xu, G. B. Hammond, Org. Lett., 2019, 21, 3848-3854.
A bromide Vilsmeier reagent promotes the conversion of primary alkyl dimethylthiocarbamates into alkyl bromides in high yields in the presence of other non-acid sensitive and non-nucleophilic functional groups.
M. F. Moynihan, J. W. Tucker, C. J. Abelt, Synthesis, 2008, 3565-3568.
The preparation of alkenyl halides of any length from inexpensive starting reagents is reported. Standard organic transformations were used to prepare straight-chain α-olefin halides in excellent overall yields with no detectable olefin isomerization and full recovery of any unreacted starting material.
T. W. Baughman, J. C. Sworen, K. B. Wagener, Tetrahedron, 2004, 60, 10943-10948.
An efficient conversion of alcohols and β-amino alcohols to the corresponding chlorides can be carried out at room temperature in methylene chloride, using 2,4,6-trichloro[1,3,5]triazine and N,N-dimethyl formamide. Addition of NaBr allows the synthesis of bromides. Optically active carbinols react under inversion.
L. de Luca, G. Giacomelli, A. Porcheddu, Org. Lett., 2002, 4, 553-555.
The combination of triphenylphosphine and copper(I) halide catalyzes an atom transfer radical addition reaction of activated organic halides to terminal alkenes under irradiation with 365 nm light using a light-emitting diode.
O. V. Fedorov, S. I. Scherbinina, V. V. Levin, A. D. Dilman, J. Org. Chem., 2019, 84, 11068-11079.
Halofluorination of alkenes in the presence of trihaloisocyanuric acids and HF•pyridine results in the formation of vicinal halofluoroalkanes in good yields. The reaction is regioselective leading to Markovnikov-oriented products and the halofluorinated adducts follow anti-addition in the case of cyclohexene and 1-methylcyclohexene.
L. T. C. Crespo, R. da S. Ribeiro, M. S. S. de Mattos, P. M. Esteves, Synthesis, 2010, 2379-2382.
Sm(OTf)3 is an effective catalysts for a versatile and efficient halogen-promoted highly regio- and stereoselective Friedel-Crafts (F-C) alkylation of electron-rich arenes with alkenes and α,β-unsaturated carbonyl compounds in the presence of NBS or I2 as halogen sources.
S. Haira, B. Maji, S. Bar, Org. Lett., 2007, 9, 2783-2786.
A metal-free ring opening/halogenation of cycloalkanols, which combines both PPO/TBAX oxidant system and blue LEDs irradiation, provides diverse γ, δ, and even more remotely halogenated ketones in good yields under mild conditions.
R. Zhao, Y. Yao, D. Zhu, D. Chang, Y. Liu, L. Shi, Org. Lett., 2018, 20, 1228-1231.
A trifluoromethylation of alkenes or alkynes using trifluoromethanesulfonic anhydride (Tf2O) as a trifluoromethylating reagent in the presence of CuX2 (X = Br, Cl), Zn powder, and 2,2'-bipyridine affords bromo(chloro)trifluoromethylated products in good yields. CuX2 plays a dual role as the catalyst and halide source, whereas 2,2′-bipyridine acts as both the activation reagent and ligand.
Y. Ouyang, C.-L. Tong, X.-H. Xu, F.-L. Qing, Org. Lett., 2021, 23, 346-350.
Unsaturated compounds such as alkenes, alkynes, allenes, and methylenecyclopropanes (MCPs) can be dibrominated within minutes by NBS and lithium bromide in THF at room temperature in good to excellent yields under mild conditions.
L.-X. Shao, M. Shi, Synlett, 2006, 1269-1271.