Categories: C-Cl Bond Formation >
Synthesis of benzyl chlorides
Recent Literature
The combination of N-chlorosuccinimide as safe chlorine source with
Acr+-Mes as the photocatalyst achieves a benzylic C-H bond
chlorination under visible light irradiation. This mild and scalable
chlorination method worked effectively for electron-deficient substrates.
Furthermore, benzylic chlorides could be converted to benzylic ethers smoothly
in one-pot by adding sodium methoxide.
M. Xiang, C. Zhou, X.-L. Yang, B. Chen, C.-H. Tung, L.-Z. Wu, J. Org. Chem., 2020, 85,
9080-9087.
A rapid, selective, and high-yielding chlorination of benzylic alcohols in the
presence of 2,4,6-trichloro-1,3,5-triazine and dimethyl sulfoxide takes 10 to 40
minutes. The neutral reaction conditions are compatible with substrates bearing
acid-labile functional groups. Both competitive intramolecular and
intermolecular reactions for benzyl alcohols in the presence of aliphatic
alcohols indicate high selectivity.
L. Sun, G. Peng, H. Niu, Q. Wang, C. Li, Synthesis, 2008,
3919-3924.
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.
A practical nucleophilic substitution of alcohols furnishes alkyl chlorides,
bromides, and iodides under stereochemical inversion in the presence of
diethylcyclopropenone as a simple Lewis base organocatalyst and benzoyl chloride
as a reagent. Moreover, acetyl chloride has been used as a stoichiometric
promotor in an invertive SN-type transformation for the first time.
T. Stach, J. Dräger, P. H. Huy, Org. Lett.,
2018, 20, 2980-2983.
The use of chloro tropylium chloride enables a rapid generation of alkyl halides
and acyl chlorides from alcohols and carboxylic acids under very mild
reaction conditions via aromatic tropylium cation activation. This reactions
demonstrate the synthetic potential of tropylium cations in promoting chemical
transformations.
T. V. Nguyen, A. Bekensir, Org. Lett., 2014,
16, 1720-1723.
The use of α,α-dichlorodiphenylmethane as chlorinating agent and FeCl3
as the catalyst enables a chlorination of alcohols and carboxylic acids to their
corresponding alkyl and acyl chlorides in high yields under mild conditions. In
the presence of LiBr or LiI, the respective alkyl bromides and iodides can be
generated.
C.-H. Lee, S.-M. Lee, B.-H. Min, D.-S. Kim, C.-H. Jun, Org. Lett.,
2018, 20, 2468-2471.
In a catalytic system for the chlorination of alcohols under Appel conditions,
benzotrichloride is used as a cheap and readily available chlorinating agent in
combination with trioctylphosphane as the catalyst and phenylsilane as the
terminal reductant under solvent-free conditions. In total, 27 different primary,
secondary, and tertiary alkyl chlorides were synthesized in good yields.
L. Longwitz, S. Jopp, T. Werner, J. Org. Chem., 2019, 84,
7863-7870.
An efficient InCl3-catalyzed reaction of secondary, tertiary and
benzylic alcohols with chlorodimethylsilane in the presence of benzil gave
the corresponding organic chlorides under mild conditions. In the absence of
benzil, the reducing products through dehydroxyhydration were obtained.
M. Yasuda, S. Yamasaki, Y. Onishi, A. Baba, J. Am. Chem. Soc.,
2004,
126, 7186-7187.
The use of sodium ion-exchanged montmorillonite enables a practical and
efficient chlorination of benzylic and allylic alcohols. The method is
characterized by the formation of hydrogen chloride from trimethylsilyl chloride
and trace water, the formation of a carbenium ion through the protonation of an
alcohol and subsequent dehydration, and the chlorination of the carbenium ion.
M. A. Tandiary, Y. Masui, M. Onaka,
Synlett, 2014, 25, 2639-2643.
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.
The Use of Bromotrichloromethane in Chlorination Reactions
S. G. Newman, C. S. Bryan, D. Perez, M. Lautens, Synthesis, 2011,
342-346.
An indium(III) hydroxide-catalyzed reaction of carbonyls and
chlorodimethylsilane afforded the corresponding deoxygenative chlorination
products. Ester, nitro, cyano, or halogen groups were not affected during
the reaction course. Typical Lewis acids such as TiCl4, AlCl3,
and BF3·OEt2 showed no catalytic activity. The
reaction mechanism is discussed.
Y. Onishi, D. Ogawa, M. Yasuda, A. Baba, J. Am. Chem. Soc., 2002,
124, 13690-13691.
The reaction of alcohols and β-amino alcohols with
2,4,6-trichloro[1,3,5]triazine and N,N-dimethylformamide in methylene
chloride at room temperature gave the corresponding chlorides, and with NaBr
gave the corresponding bromides in high yields.
L. de Luca, G. Giacomelli, A. Porcheddu, Org. Lett., 2002,
4, 553-555.
An efficient, catalytic Hunsdiecker reaction of aliphatic carboxylic acids
affords the corresponding chlorodecarboxylation products in high yields under
mild conditions in the presence of t-butyl hypochlorite and Ag(Phen)2OTf
as catalyst. The reaction exhibits remarkable functional group compatibility.
Z. Wang, L. Zhu, F. Yin, Z. Su, Z. Li, C. Li, J. Am. Chem. Soc., 2012,
134, 4258-4263.
The use of (dichloroiodo)benzene enables a mild and rapid nucleophilic
chlorination of readily available secondary and tertiary alkyl phenyl sulfides.
Enantioenriched benzylic sulfides can be converted to their corresponding
inverted chlorides with high stereospecificity. The chlorination of
sulfa-Michael derived sulfides provides elimination-sensitive β-chloro carbonyl
and nitro compounds in good yields.
D. Canestrari, S. Lancianesi, E. Badiola, C. Strinna, H. Ibrahim, M. F. A. Adamo, Org. Lett.,
2017, 19, 918-921.
Phthaloyl chloride as reagent and N-formylpyrrolidine as Lewis base
catalyst enable a transformation of aldehydes into geminal dichlorides. This
simple reaction offers mild reaction conditions, high levels of functional group
compatibility, and scalability.
P. H. Huy, Synthesis, 2019, 51,
2474-2483.
A mild and efficient protocol enables the preparation of 1,2-dichloroalkane
derivatives from olefins in the presence of NH4Cl and Oxone at room
temperature. Various terminal, internal, and cyclic alkenes reacted smoothly to
give the corresponding dichlorinated products in good to excellent yields.
Internal olefins dichlorinated with moderate to excellent diastereoselectivity.
P. Swamy, M. M. Reddy, M. A. Kumar, M. Naresh, N. Narender, Synthesis, 2014, 46,
251-257.
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.
A hypervalent iodine reagent-based α-carbonyl dihalogenation of diazoacetate
derivatives with either iodobenzene dichloride or iodotoluene difluoride results
in gem-dichlorination or gem-difluorination products, respectively.
The reaction is catalyzed by either Lewis acid or Lewis base and proceeds
rapidly and chemoselectively to the desired gem-difunctionalized products
in very good yield.
J. Tao, R. Tran, G. K. Murphy, J. Am. Chem. Soc., 2013,
135, 16312-16315.
The combination of 2-NsNCl2/2-NsNHNa as the nitrogen and chlorine sources and
copper(I) triflate as the catalyst enables a regio- and stereoselective aminochlorination
of cinnamic esters to provide anti-alkyl 3-chloro-2-(o-nitrobenzenesulfonamido)-3-phenylpropionate
derivatives with good yields and stereoselectivity.
G. Li, H.-X. Wei, S. H. Kim,
Org. Lett., 2000, 2, 2249-2252.
The regio- and stereoselective aminochlorination of α,β-unsaturated ketones
with N,N-dichloro-p-toluenesulfonamide (4-TsNCl2) and
CuOTf as catalyst provides an easy access to
vicinal haloamino ketones, with excellent regioselectivity and good yields.
Aromatic and aliphatic enones give opposite regioselectivity.
D. Chen, C. Timmons, S. Chao, G. Li, Eur. J. Org. Chem., 2004,
3097-3101.