Transcript MS PowerPoint - Catalysis Eprints database

POM catalyzed Synthesis of Methoxy methyl chloride
(MOM-Cl)
Chloromethyl methyl ether (MOM-Cl)
 Protection of alcohols, phenols, carboxylic acids, amines, -ketoesters and thiols
 A one-carbon synthon for alkylation of aromatics and active methylene derivatives
 Precursors to synthesize methyl ethers and Chloromethyl ether derivatives
 Halomethylation of aromatic systems
Production of MOM-Cl
 Conventional synthesis of MOM-Cl involves HCHO, HCl and CH3OH
 Produces the by-product bis[chloromethyl]ether (BCME)
 BCME is a powerful carcinogen and its use is seriously limited
 Requires considerable tedious handling during isolation
H. Kotsuki, Y. Ushio, N. Yoshimura and M. Ochi, J. Org. Chem. 52 (1987) 2594
D. A. Goff, R. N. Harris, J. C. Bottaro and C. D. Bedford, J. Org. Chem. 51 (1986) 4711
Synthesis of MOM-Cl using POMs as catalysts
O
O
Cl +
O
O
POM
O
+
Cl
O
0
60 C
Benzoyl chloride (1.0 mol)
Dimethoxy methane (1.0 mol)
1.5 g of (0.694 mmol) H3PW12O40
Under N2 atmosphere
Reflux at 60 C for 4 h
Cool to room temperature
Replace the reflux condenser
with distillation setup ( 60 C)
CMME or MOM-Cl (78 %)
1H
NMR was used to follow the conversion with respect to time
Integrals of the product MOM-Cl signals ( = 3.52 and 5.46 ppm) were compared with
those of dimethoxymethane ( = 3.34 and 4.56 ppm)
Conversion of Dimethoxy methane to MOM-Cl followed by 1H NMR
The reaction mixture has been analyzed with respect to time by 1H NMR
The integrals of the -CH2 signals of the reactant CH3O-CH2-OCH3 and product CH3O-CH2-Cl
were compared
Trace amount of the reaction mixture has been taken and analyzed by 1H NMR after 1h, 2h and 4h
The integrals corresponding to –CH2 signals of the reactant CH3O-CH2-OCH3 resonate
at  = 4.57
The integrals corresponding to –CH2 signals of the product CH3O-CH2-Cl resonate at  = 5.46
were found to increase with respect to time till 4 h.
The integrals of –CH2 signals of the product CH3O-CH2-Cl were found to be remained constant
after 4 h. So it was concluded that for the maximum conversion the reaction has to be carried out
for 4 h.
1H
NMR was used to follow the conversion with respect to time
Integrals of the product MOM-Cl signals ( = 3.52 and 5.46 ppm) were compared with
those of dimethoxymethane ( = 3.34 and 4.56 ppm)
MeO- CH2-OMe (--CH2--- 4.57 , --CH3--3.36)
3.852
After 1 h
MeO-CH2-Cl ( --CH2---5.46, --CH3—3.51)
4.162
After 2 h
4.709
After 4 h
(CH3-O-CH2-Cl)
1H
NMR (CDCl3) of isolated MOM-Cl by simple distillation
ppm
Effect of various POMs in the synthesis of MOM-Cl
Entry
b
c
Catalyst
Reaction
time (h)
Yield b (%)
TOF c (h−1)
1
H3PW12O40
4
79
26
2
H4SiW12O40
4
66
16
3
H3PMo12O40
4
59
12
4
Cs2.5H0.5PW12O40
4
58
21
5
H2SO4
64
74
2
Isolated yield.
TOF: moles of MOM-Cl produced per mol of catalyst per hour
The general trend for acid strength among the common heteropolyacids is
H3PW12O40 > H4SiW12O40 ≥ H3PMo12O40
I. V. Kozhevnikov, Russ. Chem. Rev. 56 (1987) 811
M. Misono, N. Mizuno, K. Katamura, A. Kasai, Y. Konishi, K. Sakata, T. Okuhara,
Y. Yoneda, Bull. Chem. Soc. Jpn. 55 (1982) 400
Features of the process
 High Bronsted acidity of POMs has been well exploited for the synthesis of
valuable reagent MOM-Cl
 POM function in both heterogeneous and homogeneous
 Simple distillation to separate the MOM-Cl
 Maximum yield of the MOM-Cl is 78 % after 4h
 Absence of carcinogenic byproduct bis[chloromethyl]ether was observed
 The process can be extended for the synthesis of other R-O-CH2-Cl by suitably
employing various other acetals
P. S. Kishore, B. Viswanathan, T. K. Varadarajan, Tetrahedron Lett. 47 (2006) 429