E
A. G. Pemba, S. A. Miller
Cluster
Synlett
water (6.355 eV) is greater than that of the acetal (5.125–
5.335 eV). This acetal electron availability/polarizability
probably arises from electronic communication between
the two acetal oxygen atoms via, in part, anomeric interac-
tions. Computationally, water has – = 0.100 while the anti-
anti acetal has – = 0.184 for the attack of protonated ace-
tal, the RDS proposed in the mechanism of Scheme 2. To be
sure, a value of – = 0.184 does not indicate a strong nucleo-
phile. By this analysis, acetal nucleophilicity (attacking
EtOCH2O(H+)Et) is between that of ethanol (– = 0.157) and
ethylamine (– = 0.217). Nonetheless, the comparatively
good nucleophilicity of acetals helps to rationalize the un-
usual third-order kinetics described in Scheme 2, depicting
an acetal attacking a protonated acetal.
Note that the RDS of Scheme 2 is analogous to that pro-
posed for the hydrolysis of sucrose (an acetal), which has a
rate = k[H+][sucrose][H2O] when not conducted under
pseudo-first-order conditions.26 In 1920, Jones and Lewis
concluded that the sucrose hydrolysis reaction (also known
as inversion) ‘is a true bimolecular one, between a molecule
of water and a complex ion, formed by the addition of hy-
drogen ion to the sucrose molecule.’27 The RDS of Scheme 2
similarly proposes the nucleophilic attack of a protonated
acetal. Importantly, the pre-equilibrium constant for [p-
TsOH] + [acetal] ↔ [acetalH+] + [p-TsO–] is small because the
pKa of p-TsOH (–2.8) is greater than that of protonated ace-
tal (–4.4).22 With a much stronger acid, the acetal metathe-
sis reaction would exhibit pseudo-second-order kinetics
with rate = [acetalH+][acetal].
4 hours at 80 °C and in 1 hour at 90 °C. The disappearance
of acetal is a third-order reaction, with a proposed rate =
k[H+][acetal]2 and a proposed RDS involving attack of a pro-
tonated acetal by an acetal. This is at odds with the consen-
sus mechanism of acetal hydrolysis, for which the rate is
second order with rate = k[H+][acetal]; the RDS is formation
of the oxonium ion electrophile, which is attacked by water,
a weak nucleophile. The higher-order reaction of acetal me-
tathesis is rationalized by the greater nucleophilicity of ace-
tal compared to water, which has been computed (–
=
0.184 eV) to be between that of water (– = 0.100 eV) and
ethylamine (– = 0.217 eV). We have previously reported
that heating linear diols with acetals ROCH2OR in the pres-
ence of acid catalysts yields polyacetals, RO–
[CH2O(CH2)nO]x–CH2OR.6 Based on the sequence of distil-
lates from this polymerization and the aforementioned ki-
netic study, a composite mechanism has been proposed.
Transacetalization with the diol occurs first, yielding bisac-
etals and this is followed by a step-growth acetal metathe-
sis mechanism, conceptually similar to that of acyclic diene
metathesis (ADMET).16
While olefin metathesis reactions seem to dominate the
metathesis literature, other functional group metatheses
have proven chemically facile and useful. In particular, we
have reported polymerization variants of acetal metathe-
sis,6 silicon acetal metathesis,8 carbonate metathesis,9 and
oxalate metathesis.10 Additional functional group metathe-
sis reactions are likely to be identified and exploited—espe-
cially for polymerization.
The attack of protonated acetal by an acetal yields the
trivalent oxonium ion shown in Scheme 2, along with etha-
nol as the leaving group. Productive acetal metathesis re-
Funding Information
+
quires the trivalent oxonium ion to lose EtOCH2 , yielding
This research was supported by the National Science Foundation
also the fully metathesized acetal (a polyacetal) at the top of
Scheme 2. The complementary metathesis product,
EtOCH2OEt, is formed when ethanol adds to EtOCH2 and
(CHE-0848236 and CHE-1607263) and the University of Florida.
N
ati
o
n
a
lS
c
i
e
n
c
e
F
o
u
n
d
ati
o
n
(C
H
E-0
8
4
8
2
3
6)Nati
o
n
a
lS
c
i
e
n
c
e
F
o
u
n
d
ati
o
n
(C
H
E-1
6
0
7
2
6
3)
+
Supporting Information
subsequently loses a proton.
In order to confirm the independent operation of the
acetal metathesis half of Scheme 2, we synthesized and iso-
Supporting information for this article is available online at
S
u
p
p
orit
n
gInformati
o
n
S
u
p
p
orit
n
gInformati
o
n
lated
the
bisacetal
from
1,10-decanediol:
EtOCH2O(CH2)10OCH2OEt.6,28 The pure bisacetal was com-
bined with 1 mol% of p-TSA catalyst. Polymerization ensued
during a 1 hour temperature ramp up to 125 °C, followed by
vacuum at 200 °C for 2 hours. Volatile EtOCH2OEt was ex-
haustively removed before the normal polymer workup
yielded polydecylene acetal in 95% yield as a white powder.
Gel-permeation chromatography (GPC) analysis showed ob-
vious conversion into polymer with Mw = 40,200 Da, Mn =
22,000 Da, and Đ = 1.83 (see the Supporting Information).
Carothers’ statement that ‘acetal interchanges are
smoothly reversible reactions’14 has been addressed herein
with a detailed kinetic analysis. The acid-catalyzed acetal
metathesis of MeOCH2OMe and EtOCH2OEt to yield
MeOCH2OEt is reasonably fast, with equilibrium reached in
References and Notes
(1) Currently at: Intel Corporation, Ronler Acres Campus, 2501 NE
Century Blvd., Hillsboro, OR 97124, USA.
(2) Handbook of Olefin Metathesis, 2nd ed; Grubbs, R. H.; Wenzel, A.
G., Ed.; Wiley-VCH: Weinheim, 2015.
html/M/M03878.html (accessed April 25, 2019).
(5) Miller, S. A.; Pemba, A. G. US Patent 9217058, 2015.
(6) Pemba, A. G.; Flores, J. A.; Miller, S. A. Green Chem. 2013, 15, 325.
(7) (a) Chikkali, S.; Stempfle, F.; Mecking, S. Macromol. Rapid
Commun. 2012, 33, 1126. (b) Rajput, B. S.; Chander, U.; Arole, K.;
Stempfle, F.; Menon, S.; Mecking, S.; Chikkali, S. H. Macromol.
Chem. Phys. 2016, 217, 1396. (c) Hufendiek, A.; Lingier, S.; Du
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–F