26
Letters in Organic Chemistry, 2011, Vol. 8, No. 1
Bálint et al.
In conclusion, the onium salts may be suitable alkylating
described for the solventless alkylations, but in this case
ethyl acetate did not have to be added.
agents under MW and solventless conditions using Cs2CO3.
Due to the MW absorbing ability of the onium salts, these
alkylations take place relatively fast.
Table 5. The Benzylation of Phenol and 4-Chlorophenol with
TEBAC using Cs2CO3 under Solventless and MW
Conditions at 150 °C for 5 min
MW
OH
OBn
150 °C / 5 min
Cs2CO3
Y
4-YC6H4OH
4-YC6H4OBn
Entry
BnEt3N+ Cl-
(1.2 eq.)
(%)a,b
+
no solvent
H
Cl
9 (8a)
20 (8b)
9 (1)
90 (8a)
78 (8b)
89 (2)
1
2
3
Y
Y
Y = H (a), Cl (b)
8
9
Me
Scheme 3.
aAt least from two independent measurements.
bThe missing quantity (1-2%) covers by-products.
Compound 2: yield: 74 %1H NMR (CDCl3) ꢁ 2.28 (3H,
Me), 5.03 (2H, CH2), 6.86–7.09 (4H, ArH-1), 7.29–7.43 (5H,
ArH-2); the data are identical with those described for an
3. EXPERIMENTAL
3.1. General
authentic sample [8]; (M+H)+
requires 199.1123.
= 199.1118, C14H15O
The alkylations were carried out in a CEM Discover [300
W] microwave reactor equipped with a pressure controller
using 5-15 W irradiation. The length and diameter of the vial
used was 8.8 and 1.3 cm, respectively.
found
Compound 7: yield: 47%; 1H NMR (CDCl3) ꢁ 0.88–0.98
(3H, CH2CH3 ), 1.41–1.54 (2H, CH2CH3), 1.69– 1.78 (2H,
OCH2CH2), 2.26 (3H, ArCH3), 3.89–3.93 (2H, OCH2), 6.78
(2H, ArH-1), 7.05 (2H, ArH-2); the compound was
described [10], but no 1H NMR data were found in the
literature; (M+H)+ = 165.
GC was carried out on an HP5890 series 2 GC-FID
chromatograph, using a 15 m ꢀ 0.18 mm Restek, Rtx-5
column with a film layer of 0.20 μm. The temperature of the
column was initially held at 40 °C for 1 min, followed by
programming at 25 °C/min up to 300 °C, and a final period
at 300 °C (isothermal) for 10 min. The temperature of the
injector was 290 °C, and of the FID detector 300 °C. The
carrier gas was H2.
1
Compound 9a: yield: 75%; H NMR (CDCl3) ꢁ 5.17
(2H, CH2), 7.06–7.57 (10H, ArH); the data are identical with
those described for an authentic sample [11]; (M+H) = 185.
1
Compound 9b: yield: 63%; H NMR (CDCl3) ꢁ 5.08
GC-MS was also carried out on an Agilent 6890 N-GC-
5973 N-MSD chromatograph, using a 30 m ꢀ 0.25 mm
Restek, Rtx-5SILMS column with a film layer of 0.25 μm.
The initial temperature of column was 45 °C for 1 min,
followed by programming at 10 °C/min up to 310 °C and a
final period at 310 °C (isothermal) for 17 min. The
temperature of the injector was 250 °C. The carrier gas was
He and the operation mode was splitless.
(2H, CH2), 6.95 (2H, ArH-1), 7.29 (2H, ArH-2), 7.38–7.46
(5H, ArH-3); the data are identical with those described for
an authentic sample [11]; (M+H)+ = 219 (for the 35Cl
isotope).
ACKNOWLEDGEMENTS
This project was partially supported by the Hungarian
Scientific Research Fund (OTKA K067679 and K83118).
This work is connected to the scientific program of the
"Development of quality-oriented and harmonized R+D+I
strategy and functional model at BME" project. This project
is supported by the New Hungary Development Plan (Project
ID: TÁMOP-4.2.1/B-09/1/KMR-2010-0002). Grants from
Richter Plc. are also acknowledged. GK is grateful for the
advice of Professor Dr Harry R. Hudson (London
Metropolitan University).
3.2. General Procedure for the Benzylation of Phenol
Derivatives with Quaternary Onium Salts Under
Solventless and MW Conditions
A mixture of 1.0 mmol of phenol derivative (0.11 g of
cresol, 0.13 g of 4-chlorophenol or 0.09 g of phenol), 1.0
mmol of alkali carbonate (0.14 g of K2CO3 or 0.33 g of
Cs2CO3) and 1.2 mmol of the quaternary onium salt (273 mg
of TEBAC, 327 mg of TEBAB or 387 mg of TBAB) in a
closed vial was irradiated (5–15 W) in the microwave reactor
at the appropriate temperature for the appropriate time (see
Tables 1, 2, 4, 5). The reaction mixture was taken up in 25
mL of ethyl acetate and the suspension was filtered.
Evaporation of the volatile components provided the crude
product that was passed through a thin (ca. 2 cm) layer of
silica gel using ethyl acetate as the eluant to give an oil that
was analysed by GC–MS or GC. The results are listed in
Tables 1, 2, 4, 5.
REFERENCES
[1]
Microwaves in Organic Synthesis; Loupy, A. Ed.; Wiley-VCH,
Weinheim, 2002.
[2]
Kranjc, K.; Kocevar, M. Microwave-assisted organic synthesis.
General considerations and transformations of heterocyclic
compounds. Curr. Org. Chem., 2010, 14, 1050-1074.
Kappe, O. Controlled microwave heating in modern organic
synthesis. Angew. Chem. Int. Ed., 2004, 43, 6250-6284.
Cvengros, J.; Toma, S.; Marque, S.; Loupy, A. Synthesis of
phosphonium salts under microwave activation - Leaving group
and phosphine substituents effects. Can. J. Chem., 2004, 82, 1365-
1371.
[3]
[4]
Similar reactions were carried out in 3 mL of acetonitrile
as the solvent (see Table 3). The work-up was similar to that