Categories: C-Br Bond Formation >
Synthesis of benzyl bromides
In a continuous-flow protocol for the bromination of benzylic compounds with only a small excess of N-bromosuccinimide, the radical reactions were activated with a readily available household compact fluorescent lamp (CFL) using a simple flow reactor design based on transparent fluorinated ethylene polymer tubing. All of the reactions were carried out using acetonitrile as the solvent, thus avoiding hazardous chlorinated solvents such as CCl4.
D. Cantillo, O. de Frutos, J. A. Rincon, C. Mateos, C. O. Kappe, J. Org. Chem., 2014, 79, 223-229.
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.
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.
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 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.
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.
Aryl aldehydes couple readily with allylmetals to afford haloallylated products in the presence of boron trihalides. The reactions tolerate a variety of functional groups. Simple aqueous workup of haloallylation reactions, followed by treatment with 1,8-diazabicyclo[5.4.0]undec-7-ene, provides a straightforward route to synthetically useful (E)-1,3-dienes.
M. P. Quinn, M.-L. Yao, G. W. Kabalka, Synthesis, 2011, 3815-3820.