Mendeleev
Communications
Mendeleev Commun., 2020, 30, 238–240
An expedient one-pot synthesis of benzophenone
Schiff bases from benzene
Irena S. Akhrem,* Lyudmila V. Afanas’eva, Dzhul’etta V. Avetisyan,
Oleg I. Artyushin and Nikolai D. Kagramanov
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. E-mail: cmoc@ineos.ac.ru
DOI: 10.1016/j.mencom.2020.03.037
A simple and efficient one-pot synthesis of benzophenone
Schiff bases from benzene, CCl4 and aromatic amines was
developed based on the the reaction of benzene with
CCl4·AlCl3 complex. This method affords Ph2CCl2 as well as
the products of its subsequent reaction with aromatic amines,
benzophenone Schiff bases, selectively and in good yields.
NAr
ArNH2
one-pot
+ CCl4·AlCl3
2
Keywords: one-pot synthesis, benzene, Schiff bases, tetrachloromethane, benzophenone, aluminum trichloride.
Benzophenone Schiff bases demonstrate promising activity against
different bacterial and fungal strains1 as well as are used as catalysts
and multipurpose reactants.2 Numerous methods have been
developed for their synthesis.1–3 Among them, the widely used
ones originated from ketones and arylamines have definite
drawbacks.3(a) Unlike the condensation of aldehydes and aryl-
amines, the reactions of ketones require high temperatures as well
as use of catalysts and specific techniques. A set of Brønsted or
Lewis acids, dehydration agents as well as microwave, infrared or
ultrasound irradiation have been employed to carry out the
syntheses of ketone Schiff bases.3(a) Most of these procedures
suffer from low yields, long reaction times, poor functional group
tolerance, the need for elevated temperature, expensive substrates,
toxic reagents, or have a limited scope. On the other hand, the
application of a Lewis acid–base pair like AlCl3–Et3N provided
products in good yields under mild conditions.3(a) However, this
reaction required large amounts of AlCl3 and Et3N in a ratio of
[Ph2C(O)]/[AlCl3]/[Et3N] 1:1.7:5.1 and failed to produce anils
from sterically crowded anilines. Alternative procedures for the
synthesis of Schiff bases were used rarely, notwithstanding their
potential advantage.1,3(b)–(f) Generally, in more than 150 years since
the first Schiff base had been obtained,4 the development of milder
and cheaper methods for their synthesis has remained a challenge.
In this work, we have developed a simple one-pot synthesis of
benzophenone anils 2a–k from benzene, CCl4·AlCl3 complex
and aromatic amines (Scheme 1) through in situ generated
dichlorodiphenylmetane 1. The reaction can be performed in
CH2Cl2 or as a solvent-free one.
The reaction of benzene with CCl4 in the presence of AlCl3
has been known since the early 20th century (Scheme 2).5 It
involves the Friedel–Crafts alkylation of benzene with CCl3+
cation, generated from CCl4 and AlCl3 with formation of benzo-
trichloride 3. In turn, compound 3 undergoes the abstraction of
Cl– ion by the electrophile resulting in cation 4 which can
alkylate another benzene molecule affording compound 1.
Willard reported that the exchange of chlorine atom of CCl4
andAlCl3 labeled with 35Cl occurs even at –20 °C, thus indicating
the ionization of CCl4 to CCl3+ cation.6 Complex PhCCl2+AlCl4– 4
preceding the formation of dichloride 1 was found to possess
definite stability and could be stored for two weeks at 25 °C.7
The complication arises (see Scheme 2) since the electrophiles,
namely CCl3+AlCl4– if the reaction is carried out in excess CCl4,
or HCl·AlCl3 if CCl4 is used in the equimolar ratio, can initiate
the subsequent transformations of dichloride 1. Depending on
the reaction conditions, this process results in Ph3CCl,8(a)
Ph2CCl2,5(b),(c) Ph3CH8(a) or PhCCl3.8(b),(c) If the reaction is
carried out in CH2Cl2 or CHCl3, the yield of compound 1
decreases due to the side reactions of benzene and CH2Cl29(a) or
CHCl3,9(b) respectively. Several works reported on the use of CS2
as a solvent.10 Examples of the preparative use of the reaction of
Cl
Cl
AlCl3
–HCl
+ CCl4
2
1
NAr
CCl3
–
+
AlCl3
–HCl
CCl3AlCl4
CCl4
+ CCl4
ArNH2
3
2a Ar = Ph
2g Ar = 4-BrC6H4
CCl2+
AlCl4–
2b Ar = 4-MeC6H4
2c Ar = 4-MeOC6H4
2d Ar = 4-FC6H4
2e Ar = 4-ClC6H4
2f Ar = 2-ClC6H4
2h Ar = 4-O2NC6H4
2i Ar = 2,6-Me2C6H3
2j Ar = 2-O2NC6H4
2k Ar = 2-Cl-4-MeC6H3
1
–HCl·AlCl3
4
Scheme 1
Scheme 2
© 2020 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
– 238 –
Akhrem, Irena S.
