Symmetric esters by Tischtschenko reaction of aldehydes catalyzed by bi- and tridentate catalysts derived from catechol or gallol, trimethylaluminum and isopropanol

Article abstract of DOI:10.1016/S0040-4020(01)01004-3

New inexpensive aluminum-based bidentate and tridentate chelates were found to be efficient catalysts for the Tischtschenko reaction of aldehydes. The conversion of n-butanal to n-butyl n-butyrate using catechol-derived catalysts at room temperature was complete (the yield of the butyrate was 99%) in two hours. High yields of symmetric esters were obtained in the case of n-alkyl and α-branched aliphatic aldehydes whereas reactivity of unsaturated aldehydes was found to be poor. Selected reactive intermediates were studied computationally at the (pBP)/DNPP level using the Spartan program. The results of computational studies indicate that in the case of the catechol-derived catalyst bidentate chelation of two aluminum atoms to an oxygen atom of aldehyde to form a structure '(O-Al)₂O=C_Ald.' is less favorable than monodentate chelation to one aluminum atom activated by the other aluminum to form a structure 'O-Al-O-Al-O=C_Ald.'. The structure of this activated monodentate system clearly resembles more closely the transition state of the hydride-transfer step of the Tischtschenko reaction than the corresponding non-activated monodentate system 'O-Al'+'O-Al-O=C_Ald.'.

Full text of DOI:10.1016/S0040-4020(01)01004-3

TETRAHEDRON
Pergamon
Tetrahedron 57 *2001) 9867±9872
Symmetric esters by Tischtschenko reaction of aldehydes
catalyzed by bi- and tridentate catalysts derived from catechol or
gallol, trimethylaluminum and isopropanol
p
Ilkka Simpura and Vesa Nevalainen
Department of Chemistry, P.O. Box 55, FIN-00014, University of Helsinki, Finland
Received 29 May 2001; revised 10 September 2001; accepted 4 October 2001
AbstractÐNew inexpensive aluminum-based bidentate and tridentate chelates were found to be ef®cient catalysts for the Tischtschenko
reaction of aldehydes. The conversion of n-butanal to n-butyl n-butyrate using catechol-derived catalysts at room temperature was complete
*
the yield of the butyrate was 99%) in two hours. High yields of symmetric esters were obtained in the case of n-alkyl and a-branched
aliphatic aldehydes whereas reactivity of unsaturated aldehydes was found to be poor. Selected reactive intermediates were studied
computationally at the *pBP)/DNPP level using the Spartan program. The results of computational studies indicate that in the case of the
catechol-derived catalyst bidentate chelation of two aluminum atoms to an oxygen atom of aldehyde to form a structure `*O±Al) OvCAld.' is
2
less favorable than monodentate chelation to one aluminum atom activated by the other aluminum to form a structure `O±Al±O±Al±
OvCAld.'. The structure of this activated monodentate system clearly resembles more closely the transition state of the hydride-transfer step
of the Tischtschenko reaction than the corresponding non-activated monodentate system `O±Al'1`O±Al±OvCAld.'. q 2001 Elsevier
Science Ltd. All rights reserved.
1
. Introduction
to aryldioxy-bis-dialkoxyaluminum 2a *derived from
catechol) and aryltrioxy-tris-dialkoxyaluminum 3 *derived
from gallol), potentially capable of bidentate chelation.
Tischtschenko conversion *Scheme 1) of nine aldehydes
catalyzed by 2a and 3 *prepared in situ) is described
*Chart 1).
The Tischtschenko reaction *e.g. Scheme 1) opens an ef®-
cient pathway for the synthesis of symmetric esters *i.e.
RCO CH R) via a direct conversion of aldehydes through
reduction±oxidation the
Tischtschenko reaction has been known for almost a century
2
2
a
procedure.
Although
1
it is still studied by several groups.
In the present study the interest was in combining experi-
mental work with theoretical calculations. The computa-
4
Earlier studies indicate that this reaction can be carried out
using aluminum alkoxides as catalysts whereas Maruoka et
tional study was aimed at comparing structures potentially
formed when aldehydes coordinate to 2a. Structure 2b was
used as a model of 2a.
2
3
al. have recently emphasized the importance of highly reac-
tive bidentate chelating biaryldioxy-bis-dialkoxyaluminum
derivatives *both the free electron pairs of OCvO of the
reacting aldehyde are bound to Lewis acidic aluminum
atoms), such as 1, as environmentally ef®cient catalysts
for Tischtschenko reactions. In order to explore the utility
of inexpensive aluminum complexes for the purposes of
catalytic Tischtschenko reactions we turned our attention
2. Experimental results and discussion
Synthetic results of the conversion of aldehydes to
symmetric esters are summarized in Tables 1 and 2. In
Scheme 1.
Keywords: symmetric esters; Tischtschenko reaction; bidentate catalysts; tridentate catalysts.
Corresponding author. Tel.: 1358-40-5879197; fax: 1358-9-191-50466; e-mail: vesa.nevalainen@helsinki.®
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020*01)01004-3

9868
I. Simpura, V. Nevalainen / Tetrahedron 57 ꢀ2001) 9867±9872
Chart 1.
Table 1. Tischtschenko reactions *yields after ¯ash chromatography) of
aldehydes R±CHO catalyzed by 2a
immediately gave rise to an exothermic reaction. This
observation indicates that the reaction runs much faster at
the start. Indeed, about 50% of the total yield of butyl
butyrate is produced during the ®rst 30 min of the reaction
catalyzed by 2a whereas the second half takes three times
longer to form *entries 1 and 3, Table 2). In the case of 3
already 62% of butanal is converted to the ester product
Entry
R
Reaction time *h)
Yield *%)
*
entry 4; Table 2) during the ®rst 30 min *the yield is
enhanced only by about 8% during the next 30 min *entry
; Table 2)).
1
2
3
4
5
6
7
8
9
n-Propyl
n-Heptyl
n-Hept-3-yl
n-Pent-2-yl
1-Phenylethyl
c-Hexyl
t-Butyl
n-Hept-3-en-3-yl
Phenyl
2
2
2
2
2
2
2
2
23
99
83
86
89
87
96
63
3
5
The conversion of n-butanal *entry 3; Table 2) catalyzed by
2a is complete in 2 h. Although the initial rate of the conver-
sion catalyzed by 3 *entries 1 and 4, Table 2) is higher, 2a
looks more productive than 3 *entries 3 and 5, Table 2).
Furthermore, solutions of 3 were not fully homogenous. In
order to ensure reliable comparison of different aldehydes,
2a was chosen for further studies *Table 1).
58
The amount of catalyst 2a prepared in situ was 1 mol% *relative to the
amount of aldehyde).
The Tischtschenko reaction of aliphatic aldehydes gave
symmetric esters in good yields *83±99%, entries 1±6,
Table 1), except in the case of 2,2-dimethylpropanal *63%
only, entry 7, Table 1). The lower yield in the case of 2,2-
dimethylpropanal could be attributable to steric hindrance in
C *contains a t-butyl substituted 4-membered ring) that
order to rationalize the results, a plausible reaction
mechanism was considered, as depicted in Scheme 2.
In the case of 2a the catalytic cycle is potentially initiated
via a Meerwein±Ponndorf±Verley *MPV) reaction of
aldehyde complex A of 2a *Scheme 2) and subsequent
coordination of another aldehyde molecule to the active
center of the catalyst leading to the formation of B. Inter-
mediate C may form via a rearrangement reaction of the
aldehyde and alkoxide units of B. Coordination of aldehyde
to C could give rise to the rupture of the 4-membered ring of
0
hampers the formation of A *would contain three t-butyl
groups) *Scheme 2). A comparison of the yields and the size
of the R group *Table 1) reveals that the size of the group
correlates with the yield. For instance, the yield of the reac-
tion of n-butanal *entry 1, Table 1) is substantially better
than that of n-octanal *entry 2, Table 1). The lower yield
observed in the case of n-octanal could originate from the
higher ¯exibility of the *longer) alkyl chain of n-octanal. In
the case of n-octanal the long n-heptyl chain may block the
active site of C more ef®ciently than the shorter alkyl chain
0
C and the formation of hemiacetal A *a hemiacetal analog
of A, Scheme 2). A subsequent intramolecular MPV reac-
0
0
tion occurring in A could lead to the formation of B *an
ester analog of B) of which a further reaction with aldehyde
renders the product ester and regenerates B.
0
of n-butanal. Furthermore, in intermediate A the two
n-heptyl chains of the hemiacetal counterpart may wrap
In order to choose reaction conditions for the conversions
summarized in Table 1, the catalytic performance of 2a and
the hydride to be transferred so that the rate of the MPV
0
reaction of A decreases *Scheme 2). The high yield
observed in the case of cyclohexanecarboxaldehyde *entry
6, Table 1) could be rationalized on the basis of the limited
3 was compared on the basis of reactions of n-butanal shown
in Table 2. Addition of aldehyde into the reaction vessel
Table 2. The optimal reaction time of the catalytic Tischtschenko conversion of n-butanal
a
Ligand *mol%)
a
Al *mol%)
Entry
Catalyst
Me
3
Reaction time *min)
Yield *%)
1
2
3
4
5
2a
2a
2a
3
1
1
1
0.66
0.66
2
2
2
2
2
30
60
120
30
49
77
99
62
70
3
60
Catalyst prepared in situ; reactions conducted at rt in CH Cl
2
Relative to the molar amount of n-butanal.
2
. Yields after ¯ash chromatography.
a

I. Simpura, V. Nevalainen / Tetrahedron 57 ꢀ2001) 9867±9872
9869
of the alkyl chain and allow faster uptake of the reactant
aldehyde than in the case of n-octanal *entry 2, Table 1).
The results shown in Table 1 *entries 8 and 9) indicate that
the conversion rates of conjugated unsaturated aldehydes
are lower than those of the corresponding saturated ones
*entries 3/8 and 6/9, Table 1). The lower reactivity could
be attributable to the higher stability of conjugated alde-
hydes that decreases the rate of MPV reactions *for both
0
tion of C and A should be lower in the case of conjugated
formation of B and B , Scheme 2). Also the rate of forma-
0
aldehydes because the formation of the hemiacetal structure
leads to the rupture of conjugation.
2.1. Computational studiesÐmethods and models
Two simple isomeric analogs 4 *activated via chelation,
Scheme 3) and 5 *not activated via chelation) of aldehyde
adduct of 2b were used as models of aldehyde adducts of 2a.
Plausible involvement of an isomeric 7-membered chelate
ring system, in which both aluminum atoms of the catalyst
would coordinate to the oxygen of the aldehyde moiety, was
also considered using 6 as a model *Scheme 3). In 6 the
aldehyde could be more activated *via bidentate chelation)
than in 4 or 5. All computational studies were carried out
employing density functional methods using the non-local
perturbative Becke±Perdew pBP model as implemented in
4
the Spartan program *version 5.0.3). All structures were
fully optimized employing the standard options of the
program *except, in the case of 5 a constraint of one torsion
angle was used to prevent chelation).
2.2. Computational studiesÐresults and discussion
Results of the computational studies indicate that 4 is
2
1
signi®cantly *i.e. 52 kJ mol , Scheme 3) more stable than
the open chain analog 5. The 7-membered chelate system
was found to be unstable *Scheme 3) indicating that this
type of bidentate chelation is not favoring for aldehyde
adducts of 2b. A comparison of structural parameters of 4
and 5 reveals that, when the aluminum atom that binds the
aldehyde moiety *AlH2CO) is not activated *i.e. in the case of
5, Scheme 3), the aldehyde moiety is less tightly bound to
the catalyst than in complex 4 in which the Lewis acidity of
the AlH2CO center is enhanced by the other aluminum atom
*of the 5-ring), that coordinates on the adjacent phenoxyl
oxygen. When the chelate structure is formed *5!4,
Scheme 2.
ability of the c-hexyl group to move and disturb the active
center of the catalyst *Scheme 2). The better performance
observed in the case of a-substituted aldehydes *entries
3
±5, Table 1) could be explained on the same basis. The
a-substituents of 2-ethylhexanal, 2-methylpentanal and
-phenylpropanal may limit the conformational freedom
2
Scheme 3) the Al±O
bond shortens signi®cantly and
H2CO
Scheme 3.

9870
I. Simpura, V. Nevalainen / Tetrahedron 57 ꢀ2001) 9867±9872
Figure 1. Optimized geometries *pBP/DNPP level) of isomers 4 and 5. For the optimization of isomer 5 the trigonal aluminum was forced to the plane of the
aromatic ring by ®xing the torsion angle C±C±O±Al to zero degrees.
Ê
the attractive electrostatic interaction between one of the
HH2CO atoms and one of the oxygens of the adjacent
newly formed 1.958 A long dative Al±O bond between the
aluminum atom of the 5-ring and the oxygen of the aryloxy
group *OArO) adjacent to the AlH2CO center *Fig. 1).
Although this bond is clearly longer than any other of the
Al±O bonds of 4 or 5 its formation has clear consequences.
The bond between the OArO and AlH2CO atoms lengthens
methoxyl groups *the distance between these atoms is
Ê
2
.424 A in 5, Fig. 1) is replaced with a favoring electrostatic
HMeO±CH2CO interaction. When the reaction 5!4 occurs,
Ê
distance shortens by 517 mA *Scheme 3).
In 4 the HMeO±CH2CO distance is surprisingly short, only
the HMeO±C
H2CO
Ê
64 mA and consequently the Lewis acidity of the adjacent
AlH2CO center increases substantially. This enhanced Lewis
acidity is re¯ected by all off-ring Al±O bonds of the AlH2CO
Ê
center. They all shorten *4, 31 and 33 A, Scheme 3, Fig. 1).
Both OMeO±Al bonds of the trigonal aluminum center of 5
also shorten slightly. The Al±OArO bond of the trigonal
Ê
1
lengthens by 29 mA and the adjacent *C±O)
.888 A *Fig. 1). Consequently, also the *H±C)
Ê
bond
shortens
MeO
MeO
Ê
by 28 mA *Scheme 3), respectively. Interestingly, the
geometry of the AlH2CO center of 4 is highly favorable for
the hydride-transfer to occur *much more favorable than in
Ê
aluminum lengthens 78 mA whereas the adjacent C ±O
Ê
bond shortens by 22 mA *Scheme 3).
5
, Fig. 1). In the case of a real working catalyst, the value of
Ar
the corresponding HRO±CRCHO distance would depend
signi®cantly on the substituents of the alkoxy group *HRO
donator) and the aldehyde moiety *HRO acceptor).
In summary, inspection of all changes of bond lengths
described above leads to the same rational conclusion:
When the reaction 5!4 occurs *Scheme 3): *a) a dative
When the chelate 4 is formed *via 5!4, Scheme 3) there is a

I. Simpura, V. Nevalainen / Tetrahedron 57 ꢀ2001) 9867±9872
9871
Al±O bond is formed, *b) other bonds of the aluminum
forming the dative bond lengthen, *c) the *MeO) Al±
OvCH moiety at the oxygen end of the dative bond
2
n-butanal *1.1 ml, 12 mmol) drop-wise into the reaction
¯ask containing the catalyst *under argon). The resulting
mixture was stirred at rt for 2 h, quenched by adding
5 mL of HCl *0.5 M in water) and extracted with diethyl
ether *3£10 mL). The combined extracts were dried over
2
moves away from the newly formed 5-ring, *d) the Lewis
acidity of the aluminum atom of the *MeO) Al±OvCH
2
2
moiety increases, and *e) the distance between one of
hydrogens *of MeO) and the CCvO shortens. Because the
geometry of the *MeO) Al±OvCH moiety of 4 resembles
MgSO . After ¯ash chromatography *ethyl acetate/hexane
4
1:4) gave n-butyl n-butyrate *845 mg, 5.9 mol) as colorless
oil *99% yield). The other esters were prepared in the same
2
2
1
13
clearly more closely the transition state of the hydride-
transfer step of the Tischtschenko reaction than the corre-
sponding system of 5 does, we conclude that there could be
clearly a co-operative effect of two aluminum atoms also in
aldehyde complexes of the original catalyst 2a favoring the
Tischtschenko reaction that occurs via an intermediate
analogous to 4 *Scheme 3).
way. The esters gave the following H and C NMR
spectrometric data.
4.4. Spectroscopic data
1
13
H NMR and C NMR data consistent with the literature in
1
the case of n-butyl n-butanoate, n-octyl n-octanoate,
1,5
1
2 c-hexylmethyl
c-hexylcarboxylate, 2,2-dimethylpropyl pivaloate, and
-methylpentyl
2-methylpentanoate,
1
,6
1,7
1
,8
3. Conclusions
benzyl benzoate.
1
.4.1. 2-Phenylpropyl 2-phenylpropanoate H NMR data
C NMR: d *two dia-
stereomers) 174.3 *CvO), 174.3 *CvO), 143.1 *C), 143.0
C), 140.4 *C), 140.4 *C), 128.5 *CH), 128.5 *CH), 128.3
CH), 128.2 *CH), 127.5 *CH), 127.4 *CH), 127.2 *CH),
Herein we have introduced a new and ef®cient method for
synthesis of symmetric esters from aldehydes. Although
the catalytic performance of 2a is not better than that of 1,
this new method has an advantage in that catalyst 2a is
inexpensive. The new catalysts can ef®ciently utilize both
straight-chain and branched-chain aldehydes, many of
which are important starting materials for industrial
processes *e.g. 2-ethylhexanal). Further studies on 2a±b
and 3 are in progress.
4
consistent with the literature.
9
13
*
*
127.0 *CH), 127.0 *CH), 126.5 *CH), 69.5 *OCH ), 69.5
2
*
1
OCH ), 45.5 *CH), 45.5 *CH), 38.9 *CH), 38.8 *CH),
2
8.2 *CH ), 18.2 *CH ), 17.7 *CH ), 17.7 *CH ).
3 3 3 3
1
.4.2. 2-Ethylhexyl 2-ethylhexanoate H NMR data
4
consistent with the literature ꢀnot all shifts given).
1
0 1
H
4. Experimental
NMR: d 4.0 *2H, d, Jˆ5.5 Hz, OCH ), 2.37±2.18 *1H, m,
2
CH), 1.75±1.13 *16H, m, CH and 2CH ), 1.00±0.86 *12H,
2
1
m, 4CH3). C NMR: d 176.5 *CvO), 66.3 *OCH ), 47.6
3
4
.1. General
2
*
*
*
CH), 38.8 *CH), 31.9 *CH ), 30.5 *CH ), 29.7 *CH ), 28.9
2 2 2
Aldehydes and all the solvents were dried, distilled and
preserved under inert atmosphere until use. Trimethyl
aluminum *2 M in toluene or heptane) was obtained from
CH ), 25.6 *CH ), 23.9 *CH ), 23.0 *CH ), 22.7 *CH ), 14.1
2
2
2
2
2
CH ), 14.0 *CH ), 11.9 *CH ), 11.0 *CH ).
3
3
3
3
1
Fluka. H NMR spectra were provided using Varian spectro-
meter at 200 MHz and C NMR spectra using Varian
1
3
Acknowledgements
spectrometer at 50.3 MHz. For all samples CDCl was
3
used as a solvent and the measurements were conducted at
2
The TEKES foundation and Dynea Chemicals Corp. are
acknowledged for ®nancial support.
1
08C. Chloroform CHCl was used as a reference for H
3
1
3
NMR spectra *7.27 ppm) and d-chloroform for C NMR
spectra *77.0 ppm). Flash chromatography was carried out
using Merck silica gel *40±63 mm) and thin layer chromato-
graphy *TLC) using Merck silica gel plates *60/F254).
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4
.2. Preparation of catalysts 2a ꢀand 3)
Under inert argon atmosphere catechol *13.2 mg,
.12 mmol; in the case of 3: 13.2 mg, 0.10 mmol of gallol
instead of catechol) was added to an oven-dried Schlenk
0
¯
1
¯
ask equipped with a stirring bar. To the ¯ask was added
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2
2
2
of Me Al *0.12 ml, 0.24 mmol) was added followed by stir-
3
ring at rt for 30 min. Addition of isopropanol *0.037 mL,
0
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2
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.3. The Tischtschenko reactions
The reaction was initiated by adding freshly distilled
4

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48 *shifts of OCH and one CH group reported only).