Friedel-Crafts Alkylation

Schematic representation of the Friedel-Crafts Alkylation.

Mechanism of the Friedel-Crafts Alkylation

Mechanism of the Friedel-Crafts Alkylation

Original publication	Compt. Rend.. 1877, 84, 1392. J. Org. Chem.. 1993, 58, 4656.
Reviews	Angew. Chem. Int. Ed.. 2004, 43, 550. Beilstein J. Org. Chem.. 2010, 0, 6. Chem. Rev.. 2008, 108, 2093. Chem. Soc. Rev.. 2009, 38, 2190. Org. React.. 1946, 3, 1.

Sample reactions

intermediate structure

intermediate structure

HCl

EtOH, H2O

Reflux, 60 min, 55%

intermediate structure

intermediate structure

NaH, PrenylBr

PhMe

35 °C, 19 h, 73%

intermediate structure

intermediate structure

Sc(OTf)3

Sealed tube

DCE, H2O

120 °C, 36 h, 73%

intermediate structure

intermediate structure

TsOH

PhMe

RT, 16 h, 55% (2 steps)

intermediate structure

intermediate structure

Br2

CH2Cl2

-78 °C to RT, 4 h, 81%

intermediate structure

intermediate structure

Br2

CH2Cl2

-78 °C to RT, 4 h, 53%

intermediate structure

intermediate structure

AgOTf, DBU, 2,6-Di-tert-butyl-4-methylpyridine

PhMe

RT, 13.5 h, 70%

intermediate structure

intermediate structure

H3PO4

Dean-Stark

Xylene(s)

Reflux, 2 h, 91%

intermediate structure

intermediate structure

AlBr3

PhH

40 °C to Reflux, 42 h, 80%

intermediate structure

intermediate structure

H3PO4

Dean-Stark

Xylene(s)

Reflux, ON, 92%

intermediate structure

intermediate structure

AlBr3

PhH

RT to 50 °C, 7 d, 88% (2 steps)

intermediate structure

intermediate structure

AlBr3

PhH

RT, 3-5 d, 57% (2 steps)

intermediate structure

intermediate structure

PPA

120 °C, 12-60 h, 91%

intermediate structure

intermediate structure

H3PO4

Soxhlet (4 Å MS)

Xylene(s)

Reflux, 25-30 h, 40% (2 steps)

intermediate structure

intermediate structure

H3PO4

Dean-Stark

Xylene(s)

Reflux, 5-8 h, 33%

intermediate structure

intermediate structure

AlBr3

PhH

RT, 3 d, 40%

intermediate structure

intermediate structure

H2SO4

Acetone, H2O

0 °C, 2 h, 80%

intermediate structure

intermediate structure

intermediate structure

SnCl4

CH2Cl2

RT, 30 min, 98%

intermediate structure

intermediate structure

LiClO4, Bi(OTf)3

4A MS

CH2Cl2

RT, 4.5 h, 94%

intermediate structure