Sodium–Oxygen Compounds

high yield (Scheme 33). Of the tetrabutylammonium salts tested as catalysts, the most efficient
is the hydrogen sulfate and the least is the perchlorate, with the results for the iodide
lying in between. [306]
Scheme 33 Phase-Transfer-Catalyzed Synthesis of Dialkyl Ethers [305,306]
R 1 OH
39
R2Cl (excess) or Me2SO4 (1.2 equiv)
50% aq NaOH, Bu4NHSO4 or TBAI (cat.)
petroleum ether or no solvent, 30−65 oC, 1.5−24 h
47−93%
R 1 OR 2
R 1 = Bu, CH 2t-Bu, (CH 2) 4Me, CH(Me)CH 2CH 2Me, (CH 2) 5Me, (CH 2) 6Me, (CH 2) 7Me, CH 2CH 2OBu, Bn, (CH 2) 2Ph
CHMePh, CMe2Ph, Tr, CH2CH CH2, CH2CH CHPh; R 2 = Et, Bu, Bn
Under phase-transfer catalysis conditions, acid-labile hemiketals undergo methylation
with iodomethane in yields exceeding 95%, [307] while benzyl alcohol undergoes reaction
to displace one bromine in 1,4-dibromobutane in 88% yield. [308] Dimethylation of chiral
1,2-disubstituted ethane-1,2-diols takes place in yields of 93–95%. [309] An analogous process
occurs when poly(ethylene glycol)s (except for the parent diol and diethylene glycol) are
treated with excess chloromethane or dimethyl sulfate in the presence of powdered sodium
hydroxide in benzene. [310] On the other hand, 50% aqueous sodium hydroxide is used
without a quaternary catalyst (Q + X – ) in monoalkylation [311] or monobenzylation, [312] of
poly(ethylene glycol)s; evidently the diols or their ethers act as catalysts. The addition of
tetrabutylammonium salts does not alter the reaction rate. [311] The efficient monobenzylation
of symmetrical diols occurs in the presence of powdered sodium hydroxide and
15-crown-5 in tetrahydrofuran. [313] The hydrophilic properties of polyols (e.g., pentaerythritol
[314,315] or carbohydrates [316,317] ) does not preclude their etherification by phasetransfer
catalysis, but special conditions have to be fulfilled (e.g., a large excess of sodium
hydroxide is required). In cases involving slowly reacting alcoholates, the formation of
symmetrical ethers (by solvolysis of the alkyl halides to the corresponding alcohols and
subsequent alkylation) competes with the formation of the nonsymmetrical ones. [304,306]
Chemical modification of cinchonidinium salts consists of their O-allylation in a 50% aqueous
sodium hydroxide–dichloromethane system. [318] 2-Ethoxyphenol, an important intermediate
in perfumery, is synthesized by alkylation of ethanol with 2-chlorophenol, using
phase-transfer catalysis under microwave irradiation. [319] gem-Dichlorocyclopropanes substituted
with electron-withdrawing groups undergo reaction with the anions generated
from phenols [44,320] or alcohols, [320] affording the respective cyclopropanone acetals.
Phenols undergo facile alkylation [321–323] or nitroarylation [322] under phase-transfer catalysis
conditions with a variety of alkylating agents; even 2,6-disubstituted, sterically
crowded phenols undergo efficient methylation (Scheme 34). [321] The ambident 2-naphthol
anion is exclusively O-alkylated. [321] The reaction of 1-bromo-3-chloropropane with
phenols under phase-transfer catalysis conditions affords 3-chloro- and small amounts
of 3-bromopropyl aryl ethers via halogen exchange. [324]
Scheme 34 Phase-Transfer-Catalyzed Synthesis of Alkyl Aryl Ethers [321–323]
Ar 1 OH
FOR INTERNAL USE ONLY
1034 Science of Synthesis 8.2 Sodium Compounds
A: R1X (2−3 equiv), ~1.2% aq NaOH, CH2Cl2
Bu3NBnBr (cat.), TBAB (1 equiv), rt, 2−12 h
B: R1X (1−2 equiv), 5 M NaOH, [Me(CH2)7]3NMeCl (cat.), reflux, 1 h
52−96%
Ar1 = Ph, 2-Tol, 2-MeOC6H4, 4-MeOC6H4, 2-O2NC6H4, 3-O2NC6H4, 4-O2NC6H4, 2-HO2CC6H4, 4-OHCC6H4 2-PhC6H4, 4-t-BuC6H4, 2,4-Cl2C6H3, 2-iPr-5-MeC6H3, 2,6-Me2C6H3, 2,4,6-t-Bu3C6H2, 1-naphthyl, 2-naphthyl, 8-quinolyl
R H2 CH2, Bn, CH2Bz, CHMePh, CH2CO2Et X = OSO3Me, OSO3Et, Cl, Br, I
1 = Me, Et, Bu, (CH2) 4Me, (CH2) 5Me, (CH2) 7Me, CH2C 40
Ar 1 OR 1
A. Jończyk and A. Kowalkowska, Section 8.2.4, Science of Synthesis, 2006 Georg Thieme Verlag KG