Efficient and simple approaches towards direct oxidative esterification of alcohols

Article abstract of DOI:10.1002/chem.201403786

The present article describes novel oxidative protocols for direct esterification of alcohols. The protocols involve successful demonstrations of both "cross" and "self" esterification of a wide variety of alcohols. The cross-esterification proceeds under a simple transition-metal-free condition, containing catalytic amounts of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy)/TBAB (tetra-n-butylammonium bromide) in combination with oxone (potassium peroxo monosulfate) as the oxidant, whereas the self-esterification is achieved through simple induction of Fe(OAc)₂/dipic (dipic=2,6-pyridinedicarboxylic acid) as the active catalyst under an identical oxidizing environment. One-pot oxidative esterification: A wide variety of alcohols undergo transition-metal-free (in the presence of oxone/2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)/tetra-n-butylammonium bromide (TBAB)) selective "cross" esterification in moderate to excellent yields (see Figure). The "self" esterification process has however been achieved in the presence of Fe(OAc)₂/2,6-pyridinedicarboxylic acid (dipic) as the active catalytic species under a similar oxidizing environment.

Full text of DOI:10.1002/chem.201403786

DOI: 10.1002/chem.201403786
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&
Alcohol Esterification
Efficient and Simple Approaches Towards Direct Oxidative
Esterification of Alcohols
Ritwika Ray, Rahul Dev Jana, Mayukh Bhadra, Debabrata Maiti,* and Goutam Kumar Lahiri*[a]
Abstract: The present article describes novel oxidative pro-
tocols for direct esterification of alcohols. The protocols in-
volve successful demonstrations of both “cross” and “self”
esterification of a wide variety of alcohols. The cross-esterifi-
cation proceeds under a simple transition-metal-free condi-
tion, containing catalytic amounts of TEMPO (2,2,6,6-tetra-
methyl-1-piperidinyloxy)/TBAB (tetra-n-butylammonium bro-
mide) in combination with oxone (potassium peroxo mono-
sulfate) as the oxidant, whereas the self-esterification is ach-
ieved through simple induction of Fe(OAc)2/dipic (dipic=
2,6-pyridinedicarboxylic acid) as the active catalyst under an
identical oxidizing environment.
Introduction
and straightforward approach would be the direct esterifica-
tion of alcohols primarily due to their easy availability and
cost-effectiveness.[6–15] In this context, the initial approach by
Milstein[6a–c] followed by Beller[6d] of acceptorless dehydrogena-
tion of primary alcohols to esters by Ru-pincer complexes are
commendable.[7] Precious metals such as Ru[8] and Rh[9]-cata-
lyzed esterification of primary alcohols in the presence of hy-
drogen acceptors[10] were also reported. A few Ir complexes
were also shown to catalyze this type of reaction.[11] Palladium-
catalyzed esterification of primary alcohols in the presence of
O2 as the terminal oxidant was reported by Lei[12] and Beller.[13]
However, these methods made use of either an expensive Ag
additive[12a] or a combination of an expensive additive and
a ligand.[13] Very recently, Beller also demonstrated esterifica-
tion of alcohols using reusable heterogeneous Co3O4-N@C cat-
alysts.[14] However, development of more sustainable reaction
protocols under homogeneous conditions demand further ex-
ploration.[15]
Ester groups are ubiquitous in various natural products, agro-
chemicals, and in commonly used synthetic scaffolds. They
constitute the backbone of several drugs as well as function as
the building blocks of various polymers, such as polyethylene
terephthalate (PET) (Figure 1). The characteristic odors of esters
have made them useful constituents for artificial fragrances
In this regard TEMPO-catalyzed oxidation of alcohols to alde-
hydes and ketones in the presence of either NaNO2 or oxone
as the oxidant was reported by Hu[16a] and Bolm (Scheme 1).[16b]
Furthermore, Borhan[16c] reported oxidation of aldehydes to
esters and acids using oxone as the sole oxidant (Scheme 1).[17]
These studies have been the incentive for the present article,
in which we demonstrate a catalytic system under transition-
metal-free conditions for the direct esterification of a wide vari-
ety of alcohols in the presence of oxone and catalytic amounts
of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy)[18–20] and TBAB
Figure 1. Ester moieties in commercially available drugs and polymers.
and flavoring agents of numerous products.[1]
Traditional esterification strategies involving reactions of car-
boxylic acids or their derivatives with alcohols[2] and carbonyla-
tion of aryl halides[3] lack eco-friendliness.[4] Though one-pot
oxidative esterification of aldehydes with alcohols has gained
considerable attention in the recent past,[5] a more convenient
[a] R. Ray, R. D. Jana, M. Bhadra, Prof. D. Maiti, Prof. G. K. Lahiri
Department of Chemistry
Indian Institute of Technology Bombay
Powai, Mumbai, 400 076 (India)
E-mail: dmaiti@chem.iitb.ac.in
lahiri@chem.iitb.ac.in
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201403786.
Scheme 1. Previous reports on metal free oxidation of alcohols and alde-
hydes.
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entry 11) for benzyl benzoate formation (Table 2). Additionally,
systematic survey of oxidants and solvents for the “self”
esterification process (Table 1, entries 11–21) indicated oxone/
toluene to be the best combination for this transformation
(Table 1, entry 11).
Subsequently, the scope and limitations of these two proto-
cols were evaluated using a wide variety of primary alcohols.
Unsubstituted benzyl alcohol reacted smoothly with MeOH
and EtOH as well as with less reactive long chain aliphatic alco-
hols, such as n-propanol, n-butanol, and n-pentanol, to give
the respective esters in good to excellent yields (Table 3, 2a–
2e).
Notably, reaction of benzyl alcohol with sterically demanding
and less reactive secondary alcohol (iso-propanol) also resulted
in the respective ester in appreciable yield (2 f). However,
when the same reaction was performed in 1:1 mixture of n-
propanol and iso-propanol, n-propyl benzoate (60%) was pro-
duced preferentially over iso-propyl benzoate (40%). This indi-
cates the affinity of benzyl alcohol to react faster with a more
nucleophilic primary alcohol (n-propanol) rather than a secon-
dary alcohol (iso-propanol) under identical reaction conditions.
As expected, the present reaction protocol also facilitated the
Scheme 2. Present protocols on direct oxidative esterification of primary al-
cohols.
(tetra-n-butylammonium bromide), leading to selective “cross”
esterification products (Scheme 2, route A). The “self” esterifica-
tion of alcohols can however be achieved in the presence of
Fe(OAc)2 in combination with 2,6-pyridinedicarboxylic acid
(dipic) as the active catalytic species (Scheme 2, route B)[21–23]
under a suitable oxidizing environment.
To the best of our knowledge, the present article highlights
the first example of a transition-metal-free direct “cross”
esterification, as well as iron-mediated “self” esterification of al-
cohols using cheap, non-toxic, and stable oxone as the oxi-
dant. This, in essence, makes the present protocols more ap-
pealing from both ecological and economical points of view.
Results and Discussion
To optimize the transformation of benzyl alcohol to
Table 1. Optimization of the critical reaction parameters.
methylbenzoate in methanol as a model system for
the direct oxidative esterification (“cross”), a variety
of oxidants was initially tested (Table 1, entries 1–8).
It was established that oxone in combination with
a catalytic amount of TEMPO (3 mol%) and TBAB
(10 mol%) resulted in the desired methylbenzoate in
90% yield (Table 1, entry 4). The presence of TEMPO
and TBAB was rather crucial because the same reac-
tion in their absence afforded methylbenzoate in
only 20% yield (Table 1, entry 1). Oxone in particular
played a key role in this direct oxidative transforma-
tion because, in its absence, benzyl alcohol remained
completely unreacted under the present reaction
conditions (Table 1, entry 2).
Entry Oxidant
Catalyst(s)
Additive/base Solvent
Yield [%]
route A: “cross” esterification[a]
2a“ 2a
1
2
3
4
5
6
7
8
oxone
–
oxone
oxone
m-CPBA
PhI(OAc)2 TEMPO
PhIO
O2 atm
–
–
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
–
–
20
–
TEMPO
–
TEMPO
TEMPO
TBAB
Na2CO3
TBAB
TBAB
TBAB
TBAB
TBAB
–
32
90
–
10
20
–
–
TEMPO
TEMPO
30
–
–
–
Toluene was employed as a solvent for the initial
optimization of the “self” esterification process, that
is, oxidative homocoupling of benzyl alcohol. Unlike
the cross esterification process, catalytic amounts of
TEMPO (2 mol%) and TBAB (8 mol%) in conjunction
with a stoichiometric amount of oxone (2.2 mmol) in
toluene afforded benzaldehyde as the major product
(60%) along with a minor quantity of benzyl ben-
zoate (20%) (Table 1, entry 9). Even the addition of
a base (Na2CO3) failed to improve the yield of desired
benzyl benzoate (Table 1, entry 10). Finally, transition-
metal catalyzed (Fe(OAc)2/dipic) esterification of ben-
zylic alcohol was realized, which led to the formation
of benzyl benzoate in 86% yield (Table 1, entry 11).
Attempts of further optimization of the “self”
esterification process using various metal salts in
combination with bi- and tridentate ligands revealed
the suitability of the Fe(OAc)2/dipic system (Table 2,
route B: “self” esterification[b]
7a“ 7a
9
10
oxone
oxone
TEMPO
TEMPO
TBAB
TBAB/
Na2CO3
toluene
toluene
60
55
20
10
11
12
13
14
15
16
17
18
19
20
21
oxone
oxone
m-CPBA
TEMPO/Fe(OAc)2/L TBAB
TEMPO/Fe(OAc)2 TBAB
TEMPO/Fe(OAc)2/L TBAB
toluene
toluene
toluene
toluene
toluene
toluene
m-xylene
xylene
THF
14
22
60
65
58
–
86
20
5
–
–
PhI(OAc)2 TEMPO/Fe(OAc)2/L TBAB
PhIO
TEMPO/Fe(OAc)2/L TBAB
TEMPO/Fe(OAc)2/L TBAB
TEMPO/Fe(OAc)2/L TBAB
TEMPO/Fe(OAc)2/L TBAB
TEMPO/Fe(OAc)2/L TBAB
TEMPO/Fe(OAc)2/L TBAB
TEMPO/Fe(OAc)2/L TBAB
O2 atm
oxone
oxone
oxone
oxone
oxone
–
45
52
28
13
6
5
10
–
–
13
1,4-dioxane
1,2-dichloroethane
[a] Benzyl alcohol (1 mmol), oxone (3 mmol), TEMPO (3 mol%), TBAB (10 mol%), 608C,
MeOH (2 mL), 48 h. [b] Benzyl alcohol (1 mmol), Fe(OAc)2 (15 mol%), L (30 mol%),
oxone (2.2 mmol), TEMPO (2 mol%), TBAB (8 mol%), 1108C, toluene (2 mL), 48 h. L=
2,6-pyridinedicarboxylic acid.
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Table 2. Optimization with various metal salts/ligands or metal com-
plexes for “self” esterification of alcohols.[a]
Table 3. Transition-metal-free direct oxidative “cross” esterification of al-
cohols.
Entry Metal salts/complexes Ligands[b] Conversion [%] Yield [%][c]
1
2
3
4
5
6
7
8
Ru3(CO)12
Ru(acac)3
RuCl3·3H2O
Ru(PPh3)2Cl2
CuSO4·5H2O
Cu(OTf)2
Cu(OAc)2
Cu(OAc)2
Fe(Pc)
Fe(NO3)3·9H2O
Fe(OAc)2
–
–
95
90
90
90
70
85
30
55
90
90
>95
70
90
75
76
73
90
92
88
90
–
–
–
–
trpy
PCy3
dipic
dipic
dppb
dipic
–
dppb
dipic
pic
dppb
dppe
PPh3
PCy3
PCy3
dipic
dipic
dipic
–
22
15
40
–
15
90 (86)
20
25
36
40
13
5
9
10
11
12
13
14
15
16
17
18
19
20
Fe(OAc)2
Fe(OAc)2
Fe(OAc)2
Fe(OAc)2
Fe(OAc)2
Fe(NO3)3·9H2O
Fe(BF4)2·6H2O
Fe(SO4)2·7H2O
Fe(ClO4)2·6H2O
–
–
–
[a] Reaction conditions: catalyst (15 mol%), ligand (30 mol%), benzyl alco-
hol (1 mmol), oxone (2.2 equiv), TEMPO (2 mol%), TBAB (8 mol%) in tolu-
ene (2 mL), 1108C, 48 h. See the Experimental Section for the details.
[b] Dipic=pyridine-2,6-dicarboxylic acid, pic=pyridine-2-carboxylic acid,
dppb=1,4-Bis(diphenylphosphino)butane, dppe=1,4-Bis(diphenylphos-
phino)ethane, PPh3 =triphenylphosphine, PCy3 =Tricyclohexylphosphine,
trpy=2,2’:6’,2’’-Terpyridine. [c] Determined by GC using n-decane as an
internal standard. Isolated yield is given in parenthesis.
Reaction conditions: benzylic alcohol (1 mmol), oxone (3 mmol), TEMPO
(3 mol%), TBAB (10 mol%), 608C, MeOH (2 mL), 48 h. [a] ROH (2 mL, R=
Et, nPr, iPr), 48 h, 758C. [b] R’OH (2 mL, R’=nBu, nPent, C6H11), 1108C.
[c] GC yields.
formation of cyclohexyl benzoate in a preparatively useful
yield (2g). Excellent yields of the corresponding methyl esters
with para- and meta-alkyl substituted benzyl alcohols (2h and
2k) were also obtained. Reactions of para-alkyl substituted
benzyl alcohols with higher alcohols also resulted in the re-
spective esters in appreciable yields (2i, 2j, and 2l).
Table 4. Transition-metal-free direct oxidative “cross” esterification of ali-
phatic alcohols.[a]
Various halogenated benzylic alcohols consistently afforded
the corresponding methyl and ethyl esters in good yields with-
out any dehalogenation process (2m–2s). Furthermore, the
present reaction conditions successfully tolerated benzyl alco-
hols containing strongly electron withdrawing ÀNO2 and ÀCF3
groups (2t–2v). Though a benzyl alcohol-containing, strongly
electron-donating ÀOMe group at the para-position failed to
yield the desired ester[16c], the ÀOMe group at the meta-posi-
tion of the phenyl ring afforded the corresponding ester in
moderate yield (2w). Complete conversion was observed for
biphenylmethanol, producing methyl biphenyl-4-carboxylate in
92% yield (2x).
Notably, under the present reaction conditions aliphatic al-
cohols, with MeOH as solvent, also underwent direct oxidative
esterification in moderate to good yields (Table 4, 4a–4c). Re-
ports on direct “cross” esterifcation of aliphatic alcohols even
in the presence of metal catalysts are rather limited. This fur-
[a] Aliphatic alcohol (1 mmol), oxone (4 mmol), TEMPO (10 mol%), TBAB
(20 mol%), 608C, MeOH (2 mL), 48 h. [b] GC Yield.
ther emphasizes the broader applicability of the present meth-
odology.
Another intriguing feature of the present methodology was
the formation of 2-hydroxyethyl benzoates and allyl benzoates
from benzyl alcohol, from reactions in which ethane-1,2-diol
(Table 5, 5a) and allyl alcohol (Table 6, 6a) were employed as
solvents. Substituted benzylic alcohols (Table 5, 5b and 5c;
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Table 5. Transition-metal-free direct oxidative “cross” esterification of
benzylic alcohols with ethane-1,2-diol as the solvent.[a]
Table 7. Metal-catalyzed direct oxidative “self” esterification of alcohols.[a]
[a] Benzylic alcohol (1 mmol), oxone (4 mmol), TEMPO (10 mol%), TBAB
(20 mol%), 1108C, ethane-1,2-diol (2 mL), 60 h.
Table 6. Transition-metal-free direct oxidative “cross” esterification of
benzyl alcohols with allyl alcohol as the solvent.[a]
[a] Benzylic alcohol (1 mmol), Fe(OAc)2 (15 mol%), dipic (30 mol%), oxone
(2.2 mmol), TEMPO (2 mol%), TBAB (8 mol%), 1108C, toluene (2 mL), 48 h. [b] GC
yields.
alkoxy-substituted benzyl alcohol (7h) but the same reaction
failed to occur for similar substitution at the para-position.[16c]
Under the present reaction conditions, aliphatic alcohols such
as 2-phenethyl alcohol, 1-octanol and its isomer, 2-ethyl-hexa-
nol, consistently afforded the desired homocoupled esters (7i,
7k, and 7l) in conjunction with a benzoate derivative in each
case (see the Supporting Information). The unusual formation
of the benzoate derivatives can be attributed to the partial oxi-
dation of the solvent toluene to benzyl alcohol and/or benzal-
dehyde[25] followed by condensation with the respective ali-
phatic alcohols, as mentioned above. However, 3-phenyl prop-
anol produced 3-phenylpropyl 3-phenylpropanoate in 81%
yield (7j) without any such unexpected esterification.
The probable mechanistic pathways for both “cross” and
“self” esterification processes have been depicted in Scheme 4.
It is logical to believe that the present reaction conditions lead
to the initial formation of an aldehyde intermediate, which
subsequently undergoes the “cross” and “self” esterification
processes in alcohol (Scheme 4, route A) and toluene
(Scheme 4, route B), respectively.
[a] Benzylic alcohol (1 mmol), oxone (4 mmol), TEMPO (10 mol%), TBAB
(20 mol%), 908C, allylic alcohol (2 mL), 60 h. [b] GC yield.
Table 6, 6b) were also well-tolerated under the respective reac-
tion conditions.
Interestingly, the C=C bond in the allylic position remained
completely intact (Table 6, 6a and 6b) even under a strong ox-
idizing environment, which highlights the novelty of the pres-
ent strategy.
The reaction of cinnamyl alcohol with MeOH as solvent af-
forded methyl benzoate in 65% yield instead of the expected
methyl cinnamate; this can be attributed to an oxidative C=C
bond cleavage process in the presence of TEMPO/oxone, lead-
ing to the initial formation of benzaldehyde, followed by
esterification in a methanolic medium (Scheme 3).[24]
Under aerobic reaction conditions, the oxidation of alcohol
to aldehyde is catalyzed by TEMPO in the presence of a stoi-
chiometric amount of oxone as the terminal oxidant.[18–20]
Oxone (acting as the secondary oxidant) initially converts
TEMPO (nitroxide) [A] to its corresponding oxoammonium
cation [B], which essentially acts as the active catalytic species
in the oxidation of alcohol to aldehyde. In the role of secon-
dary oxidant, oxone is crucial because the same reaction in its
absence led to no desired product formation. The alcohol oxi-
dation occurs with an initial hydrogen bond formation be-
tween the hydroxyl group and the oxoammonium nitrogen,
followed by simultaneous proton transfer and hydride abstrac-
tion. Subsequently, the hydroxyammonium cation [C], so
formed again, undergoes oxidation to [A], followed by the for-
mation of [B], and the catalytic cycle involving alcohol oxida-
Scheme 3. Oxidative C=C bond cleavage in the presence of TEMPO/oxone.
The Fe(OAc)2/dipic-catalyzed oxidative homocoupling of pri-
mary alcohols to the corresponding “self” esters was also
found to be effective for both the benzylic (Table 7, 7a–7h)
and aliphatic alcohols (Table 7, 7i–7l).
Clean conversions to the respective esters were observed for
various alkylated and halogenated benzylic alcohols (7b, 7c,
and 7d–7 f). In addition, para-substituted benzyl alcohol con-
taining the strongly electron-withdrawing ÀCF3 group was also
tolerated (7g). Similar to the “cross” esterification process, the
corresponding homocoupled ester was obtained for the meta-
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Table 8. Control experiments.
[a] Benzylic alcohol (1 mmol), oxone (3 mmol), TEMPO (3 mol%), TBAB
(10 mol%), 608C, MeOH (2 mL), 48 h. [b] Benzylic alcohol (1 mmol),
Fe(OAc)2 (15 mol%), dipic (30 mol%), oxone (2.2 mmol), TEMPO (2 mol%),
TBAB (8 mol%), 1108C, toluene (2 mL), 48 h.
methyl benzoate in a 1:1 ratio (Table 8). However, when the
same reaction was performed in toluene in the presence of
benzyl alcohol (1 mmol) under the optimized reaction condi-
tions for “self” esterification (Table 1, entry 11), benzyl 4-methyl-
benzoate was formed exclusively, whereas benzoic acid re-
mained completely unreacted (Table 8). It is therefore inferred
that, under the present reaction protocols, the reaction pref-
erably proceeds through the aldehyde intermediate instead of
an alternate acidic intermediate.[2]
Conclusion
In conclusion, the present article demonstrates for the first
time an operationally simple and sustainable transition-metal-
free “cross” esterification, as well as iron-mediated “self”
esterification from a wide variety of alcohols, including substi-
tuted benzyl alcohols, as well as long chain aliphatic alcohols.
The “cross” esterification strategy is rather unique in displaying
distinctive tolerance towards the selective formation of allyl
benzoates and 2-hydroxyethylbenzoates. The simplicity and
broader substrates scope underscore the novelty of the pres-
ent protocols, which may circumvent the need for the use of
precious metals in direct oxidative esterification of alcohols.
Scheme 4. Probable pathways for “cross” and “self” esterification processes.
tion thereby follows. The involvement of an aldehyde inter-
mediate in the reaction cycle is corroborated by its detection
as a minor product on all occasions (5–30%). The “cross”
esterification then proceeds by a Baeyer–Villiger oxidation
pathway, as reported earlier.[16c]
Although TEMPO-catalyzed aerobic oxidation of alcohol to
aldehyde in presence of oxone is also operational for the “self”
esterification process, the active involvement of the metal cata-
lyst, that is, Fe(OAc)2/dipic, is imperative for the desired prod-
uct formation as established by the optimization reactions
(Table 1, entry 11). Therefore, it can be proposed that for ho-
mocoupled oxidative esterification, the nucleophilic attack on
the aldehyde by the second alcohol molecule is promoted by
the Lewis-acidic character of the active Fe-dipic[5e] complex,
which in turn facilitates the formation of hemiacetal intermedi-
ate [D] (Scheme 4).[13] The hemiacetal [D] thereby undergoes
further oxidation in the presence of oxone by a Baeyer–Villiger
oxidation pathway to give the desired ester 7 (route B in
Scheme 4).[16c]
Experimental Section
General considerations
Unless otherwise stated, all reactions were carried out under air at-
mosphere in screw-cap reaction tubes. All solids were weighed in
air. Toluene, MeOH, EtOH, nPrOH, iPrOH, nBuOH, nPentanol, and cy-
clohexanol were purchased from Merck, India and used as received
without adding any drying agents. Benzyl alcohol, substituted
benzyl alcohols, aliphatic alcohols like phenethyl alcohol, 3-phenyl-
1-propanol, 1-octanol, and 2-ethyl-1-hexanol, oxone, tetrabutylam-
monium bromide, TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy),
iron(II) acetate, and 2,6-pyridinedicarboxylic acid were bought from
Aldrich, USA and were used as received. For column chromatogra-
phy, silica gel (100–200 mesh or 230–400 mesh) from Merck, India
was used. A gradient elution using petroleum ether and ethyl ace-
tate was performed based on Merck aluminium TLC sheets (silica
gel 60F254) and visualized by UV (254 nm) lamp or in an iodine
chamber depending on the product type.
The controlled experiment comprising of the reaction of
a unimolar mixture of benzoic acid and p-tolualdehyde in
methanolic solvent, under optimized reaction conditions for
“cross” esterification (Table 1, entry 4), as expected, resulted in
simultaneous formation of methyl benzoate and methyl 4-
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Analytical methods
General procedure for the synthesis of esters by oxidative
“self” esterification of benzylic alcohols
Isolated compounds were characterized by 1H NMR spectroscopy,
13C NMR spectroscopy, and gas chromatography mass spectrome-
try (GC-MS). In addition, compounds were further characterized by
To an oven-dried screw-cap reaction tube charged with a magnetic
stir-bar, Fe(OAc)2 (15 mol%, 0.15 mmol, 26.08 mg), 2,6-pyridinedi-
carboxylic acid (30 mol%, 0.30 mmol, 50.14 mg), oxone (2.2 equiv,
2.2 mmol), TEMPO (2 mol%, 0.02 mmol) and Bu4NBr (8 mol%,
0.08 mmol) were added. Depending on the physical state of ben-
zylic alcohols (1 mmol), solid compounds were weighed along with
the other reagents, whereas liquid benzylic alcohols and toluene
(2 mL) were added by microlitre syringe and laboratory syringe, re-
spectively, under air atmosphere. The reaction tube was closed
with a screw cap and kept for vigorous stirring in a preheated oil
bath at 1108C for 48 h. After completion, the reaction mixture was
cooled to room temperature, diluted with water and extracted
with 3ꢁ10 mL of ethyl acetate. The combined organic extracts
were dried over Na2SO4 and concentrated under reduced pressure.
The crude product was purified by column chromatography using
a mixture of petroleum ether/ethyl acetate as the eluent.
1
high-resolution mass spectrometry (HRMS). Copies of the H NMR
and 13C NMR spectra can be found in the Supporting Information.
Nuclear magnetic resonance spectra were recorded on a Bruker
1
400 and 500 MHz instruments. H NMR experiments were reported
in units, parts per million (ppm), and were measured relative to
the signals for residual chloroform (7.26 ppm) in the deuterated
solvent, unless otherwise stated. 13C NMR spectra were reported in
ppm relative to deuterochloroform (77.23 ppm), unless otherwise
1
stated, and all were obtained with H decoupling. All GC analyses
were performed on a Shimadzu GC-2014 gas chromatograph with
a FID detector using a J & W HP-5 column (length 50 m, inner di-
ameter 0.320 mm, film 0.52 mm) with n-decane as the internal stan-
dard. All GC-MS analyses were done using an Agilent 7890 A GC
system connected with 5975C inert XL EI/CI MSD (with triple axis
detector). ESI HRMS spectra were recorded using a BRUKER Maxis
Impact mass spectrometer.
Acknowledgements
The activity is supported by DST (G.K.L.) and CSIR (P81102,
D.M.), India (No.SB/S5/GC-05/2013) (D.M.). Financial support re-
ceived from UGC (fellowship to R.R.), New Delhi, India is grate-
fully acknowledged.
General procedure for the synthesis of esters via oxidative
“cross” esterification
Case 1: Cross esterification of benzylic alcohols with ROH
(where R=CH3, C2H5, nC3H7, iC3H7, nC4H9, nC5H11, C6H11): To an
oven-dried screw-cap reaction tube charged with a magnetic stir-
bar, oxone (3 equiv, 3 mmol), TEMPO (3 mol%, 0.03 mmol) and
nBu4NBr (10 mol%, 0.1 mmol) were added. Depending on the
physical state of benzylic alcohols (1 mmol), solid compounds were
weighed along with the other reagents, whereas liquid benzylic al-
cohols and ROH (2 mL) were added by microlitre syringe and labo-
ratory syringe, respectively, under air atmosphere. The reaction
tube was closed with a screw cap and kept for vigorous stirring in
a preheated oil bath for 48 h. The temperature of the reactions
was varied depending on the type of alcohol used as the solvent
(see the Supporting Information for details). After completion, the
reaction mixture was cooled to room temperature, diluted with
water and extracted with 3ꢁ10 mL of ethyl acetate. The combined
organic extracts were dried over Na2SO4 and concentrated under
reduced pressure. The crude product was purified by column chro-
matography using a mixture of petroleum ether/ethyl acetate as
the eluent.
Keywords: alcohols · direct oxidative esterification · iron ·
mechanistic study · transition-metal-free
[1] J. Otera, Esterification: Methods, Reactions, and Applications, Wiley-VCH,
Weinheim, 2003.
[2] R. C. Larock, Comprehensive Organic Transformations: A Guide to Func-
tional Group Preparations, 2ednd edWiley, New York, 1999.
[3] a) A. Schoenberg, R. F. Heck, J. Org. Chem. 1974, 39, 3327–3331; b) A.
Brennfꢂhrer, H. Neumann, M. Beller, Angew. Chem. 2009, 121, 4176–
4196; Angew. Chem. Int. Ed. 2009, 48, 4114–4133.
[4] a) C. F. J. Barnard, Organometallics 2008, 27, 5402–5422; b) C. F. J. Bar-
nard, Org. Process Res. Dev. 2008, 12, 566–574.
[5] a) K. Ekoue-Kovi, C. Wolf, Chem. Eur. J. 2008, 14, 6302–6315; b) W. J.
Yoo, C. J. Li, Tetrahedron Lett. 2007, 48, 1033–1035; c) W. J. Yoo, C. J. Li,
J. Org. Chem. 2006, 71, 6266–6268; d) B. Xu, X. Liu, J. Haubrich, C. M.
Friend, Nat. Chem. 2010, 2, 61–65; e) X. F. Wu, C. Darcel, Eur. J. Org.
Chem. 2009, 1144–1147; f) C. Liu, S. Tang, L. Zheng, D. Liu, H. Zhang, A.
Lei, Angew. Chem. 2012, 124, 5760–5764; Angew. Chem. Int. Ed. 2012,
51, 5662–5666; g) R. Gopinath, B. K. Patel, Org. Lett. 2000, 2, 577–579.
[6] a) J. Zhang, G. Leitus, Y. Ben-David, D. Milstein, J. Am. Chem. Soc. 2005,
127, 10840–10841; b) J. Zhang, M. Gandelman, L. J. W. Shimon, D. Mil-
stein, Dalton Trans. 2007, 107–113; c) C. Gunanathan, L. J. W. Shimon,
D. Milstein, J. Am. Chem. Soc. 2009, 131, 3146–3147; d) M. Nielsen, H.
Junge, A. Kammer, M. Beller, Angew. Chem. 2012, 124, 5809–5811;
Angew. Chem. Int. Ed. 2012, 51, 5711–5713.
[7] For recent reviews on acceptorless dehydrogenative transformations,
see: a) C. Gunanathan, D. Milstein, Science 2013, 341, 1229712; b) G. E.
Dobereiner, R. H. Crabtree, Chem. Rev. 2010, 110, 681–703.
[8] a) N. A. Owston, A. J. Parker, J. M. J. Williams, Chem. Commun. 2008,
624–625; b) N. A. Owston, T. D. Nixon, A. J. Parker, M. K. Whittlesey,
J. M. J. Williams, Synthesis 2009, 1578–1581.
Case 2: Cross esterification of: i) aliphatic alcohols with MeOH,
and ii) benzylic alcohols with ethane-1,2-diol and allylic alcohol:
To an oven-dried screw-cap reaction tube charged with a magnetic
stir-bar, oxone (4 equiv, 4 mmol), TEMPO (10 mol%, 0.1 mmol) and
Bu4NBr (20 mol%, 0.2 mmol) were added. Liquid aliphatic and ben-
zylic alcohols were added by microlitre syringe, whereas the re-
spective solvents, that is, MeOH, ethane-1,2-diol and allylic alcohol
(each 2 mL) were added by laboratory syringe under air atmos-
phere. The reaction tube was closed with a screw cap and kept for
vigorous stirring in a preheated oil bath for i) 48 h and ii) 60 h re-
spectively. The temperature of the reactions was varied depending
on the type of solvent used (see the Supporting Information for
details). After completion, the reaction mixture was cooled to
room temperature, diluted with water and extracted with 3ꢁ
10 mL of ethyl acetate. The combined organic extracts were dried
over Na2SO4 and concentrated under reduced pressure. The crude
product was purified by column chromatography using a mixture
of petroleum ether/ethyl acetate as the eluent.
[9] T. Zweifel, J. V. Naubron, H. Grꢂtzmacher, Angew. Chem. 2009, 121, 567–
571; Angew. Chem. Int. Ed. 2009, 48, 559–563.
[10] For recent reviews on hydrogen acceptors in the activation of alcohols,
see: a) T. D. Nixon, M. K. Whittlesey, J. M. J. Williams, Dalton Trans. 2009,
753–762; b) G. W. Lamb, J. M. J. Williams, Chim. Oggi 2008, 26, 17–19;
c) M. H. S. A. Hamid, P. A. Slatford, J. M. J. Williams, Adv. Synth. Catal.
2007, 349, 1555–1575.
&
&
Chem. Eur. J. 2014, 20, 1 – 8
www.chemeurj.org
6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

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[11] a) A. Izumi, Y. Obora, S. Sakaguchi, Y. Ishii, Tetrahedron Lett. 2006, 47,
9199–9201; b) N. Yamamoto, Y. Obora, Y. Ishii, J. Org. Chem. 2011, 76,
2937–2941.
[12] a) C. Liu, J. Wang, L. Meng, Y. Deng, Y. Li, A. Lei, Angew. Chem. 2011,
123, 5250–5254; Angew. Chem. Int. Ed. 2011, 50, 5144–5148; b) C. Liu,
S. Tang, A. Lei, Chem. Commun. 2013, 49, 1324–1326.
i) J. F. Greene, J. M. Hoover, D. S. Mannel, R. W. Thatcher, S. S. Stahl, Org.
Process Res. Dev. 2013, 17, 1247–1251; j) L. Tebben, A. Studer, Angew.
Chem. 2011, 123, 5138–5174; Angew. Chem. Int. Ed. 2011, 50, 5034–
5068; k) J. M. Hoover, B. L. Ryland, S. S. Stahl, J. Am. Chem. Soc. 2013,
135, 2357–2367; l) J. M. Hoover, B. L. Ryland, S. S. Stahl, ACS Catal. 2013,
3, 2599–2605.
[13] S. Gowrisankar, H. Neumann, M. Beller, Angew. Chem. 2011, 123, 5245–
5249; Angew. Chem. Int. Ed. 2011, 50, 5139–5143.
[14] R. V. Jagadeesh, H. Junge, M. M. Pohl, J. Radnik, A. Brꢂckner, M. Beller, J.
Am. Chem. Soc. 2013, 135, 10776–10782.
[20] For reviews on TEMPO-catalyzed oxidations, see: a) W. Adam, C. R.
Saha-Moller, P. A. Ganeshpure, Chem. Rev. 2001, 101, 3499–3548;
b) R. A. Sheldon, I. W. C. E. Arends, G. J. Ten Brink, A. Dijksman, Acc.
Chem. Res. 2002, 35, 774–781; c) A. E. J. de Nooy, A. C. Besemer, H. van
Bekkum, Synthesis 1996, 1153; d) N. Merbouh, J. M. Bobbitt, C. Brꢂckner,
Org. Prep. Proc. Int. 2004, 36, 1–31.
[21] a) Iron Catalysis in Organic Chemistry, (Ed.: B. Plietker) Wiley-VCH, Wein-
heim, 2008; b) Iron Catalysis: Fundamentals and Applications, (Ed.: B.
Plietker) Springer, Berlin, 2010.
[22] For selected reviews on iron catalysis, see: a) C. Bolm, J. Legros, J.
Le Paih, L. Zani, Chem. Rev. 2004, 104, 6217–6254; b) S. Enthaler, K.
Junge, M. Beller, Angew. Chem. 2008, 120, 3363–3367; Angew. Chem.
Int. Ed. 2008, 47, 3317–3321; c) B. D. Sherry, A. Fꢂrstner, Acc. Chem. Res.
[15] For more examples of direct esterification of alcohols, see: a) X. F. Bai, F.
Ye, L. S. Zheng, G. Q. Lai, C. G. Xia, L. W. Xu, Chem. Commun. 2012, 48,
8592–8594; b) R. L. Oliveira, P. K. Kiyohara, L. M. Rossi, Green Chem.
2009, 11, 1366–1370; c) H. Miyamura, T. Yasukawa, V. Kobayashi, Green
Chem. 2010, 12, 776–778; d) F. Z. Su, J. Ni, H. Sun, Y. Cao, H. Y. He, K. N.
Fan, Chem. Eur. J. 2008, 14, 7131–7135; e) A. Abramovich, H. Toledo, E.
Pisarevsky, A. M. Szpilman, Synlett 2012, 23, 2261–2265; f) X. F. Wu,
Chem. Eur. J. 2012, 18, 8912–8915; g) K. Kaizuka, H. Miyamura, S. Ko-
bayashi, J. Am. Chem. Soc. 2010, 132, 15096–15098; h) A. B. Powell, S. S.
Stahl, Org. Lett. 2013, 15, 5072–5075.
ˇ
2008, 41, 1500–1511; d) W. M. Czaplik, M. Mayer, J. Cvengros, A. J. von
[16] a) R. Liu, X. Liang, C. Dong, X. Hu, J. Am. Chem. Soc. 2004, 126, 4112–
4113; b) C. Bolm, A. S. Magnus, J. P. Hildebrand, Org. Lett. 2000, 2,
1173–1175; c) B. R. Travis, M. Sivakumar, G. O. Hollist, B. Borhan, Org.
Lett. 2003, 5, 1031–1034.
Wangelin, ChemSusChem 2009, 2, 396–417; e) C. L. Sun, B. J. Li, Z. J. Shi,
Chem. Rev. 2011, 111, 1293–1314.
[23] For recent examples of iron catalyzed synthetic transformations, see:
a) T. Matsubara, S. Asako, L. Ilies, E. Nakamura, J. Am. Chem. Soc. 2014,
136, 646–649; b) S. Asako, L. Ilies, E. Nakamura, J. Am. Chem. Soc. 2013,
135, 17755–17757; c) Z. Huang, L. Jin, Y. Feng, P. Peng, H. Yi, A. Lei,
Angew. Chem. 2013, 125, 7292–7296; Angew. Chem. Int. Ed. 2013, 52,
7151–7155; d) L. Q. Lu, Y. Li, K. Junge, M. Beller, Angew. Chem. 2013,
125, 8540–8544; Angew. Chem. Int. Ed. 2013, 52, 8382–8386; e) R. V. Ja-
gadeesh, A. E. Surkus, H. Junge, M. M. Pohl, J. Radnik, J. Rabeah, H.
Huan, V. Schuenemann, A. Brꢂckner, M. Beller, Science 2013, 342, 1073–
1076; f) E. Alberico, P. Sponholz, C. Cordes, M. Nielsen, H. J. Drexler, W.
Baumann, H. Junge, M. Beller, Angew. Chem. 2013, 125, 14412–14416;
Angew. Chem. Int. Ed. 2013, 52, 14162–14166; g) J. E. M. N. Klein, B.
Miehlich, J. Kꢄstner, B. Plietker, Dalton Trans. 2013, 42, 7519–7525; h) I.
Alt, P. Rohse, B. Plietker, ACS Catal. 2013, 3, 3002–3005; i) C. Belger, B.
Plietker, Chem. Commun. 2012, 48, 5419–5421; j) R. Ray, A. D. Chowdhu-
ry, D. Maiti, G. K. Lahiri, Dalton Trans. 2014, 43, 38–41; k) R. Ray, A. D.
Chowdhury, G. K. Lahiri, ChemCatChem 2013, 5, 2158–2161; l) A. Deb, S.
Agasti, T. Saboo, D. Maiti, Adv. Synth. Catal. 2014, 356, 705–710.
[24] a) B. R. Travis, R. S. Narayan, B. Borhan, J. Am. Chem. Soc. 2002, 124,
3824–3825; b) T. Wang, N. Jiao, J. Am. Chem. Soc. 2013, 135, 11692–
11695; c) P. Spannring, P. C. A. Bruijnincx, B. M. Weckhuysenb, R. J. M.
Klein Gebbink, RSC Adv. 2013, 3, 6606–6613.
[17] H. Hussain, I. R. Green, I. Ahmed, Chem. Rev. 2013, 113, 3329–3371.
[18] For examples of oxoammonium salt-catalyzed alcohol oxidations, see:
a) J. M. Bobbitt, J. Org. Chem. 1998, 63, 9367–9374; b) N. Merbouh,
J. M. Bobbitt, C. Brꢂckner, J. Org. Chem. 2004, 69, 5116–5119; c) J. M.
Bobbitt, A. L. Bartelson, W. F. Bailey, T. A. Hamlin, C. B. Kelly, J. Org.
Chem. 2014, 79, 1055–1067; d) J. C. Qiu, P. P. Pradhan, N. B. Blanck, J. M.
Bobbitt, W. F. Bailey, Org. Lett. 2012, 14, 350–353; e) C. B. Kelly, M. A.
Mercadante, T. A. Hamlin, M. H. Fletcher, N. E. Leadbeater, J. Org. Chem.
2012, 77, 8131–8141; f) W. F. Bailey, J. M. Bobbitt, K. B. Wiberg, J. Org.
Chem. 2007, 72, 4504–4509; g) M. Shibuya, Y. Osada, Y. Sasano, M. To-
mizawa, Y. Iwabuchi, J. Am. Chem. Soc. 2011, 133, 6497–6500; h) M. Shi-
buya, M. Tomizawa, I. Suzuki, Y. Iwabuchi, J. Am. Chem. Soc. 2006, 128,
8412–8413; i) M. Shibuya, M. Tomizawa, Y. Iwabuchi, J. Org. Chem.
2008, 73, 4750–4752; j) M. Shibuya, T. Sato, M. Tomizawa, Y. Iwabuchi,
Chem. Commun. 2009, 1739–1741.
[19] For recent examples of TEMPO-catalyzed oxidations, see: a) J. M.
Hoover, S. S. Stahl, J. Am. Chem. Soc. 2011, 133, 16901–16910; b) J. M.
Hoover, J. E. Steves, S. S. Stahl, Nat. Protoc. 2012, 7, 1161–1167; c) A.
Dijksman, A. Marino-Gonzꢃlez, A. M. i Payeras, I. W. C. E. Arends, R. A.
Sheldon, J. Am. Chem. Soc. 2001, 123, 6826–6833; d) R. Miller, R. S.
Hoerrner, Org. Lett. 2003, 5, 285; e) X. Liu, Q. Xia, Y. Zhang, C. Chen, W.
Chen, J. Org. Chem. 2013, 78, 8531–8536; f) X. Wang, R. Liu, Y. Jin, X.
Liang, Chem. Eur. J. 2008, 14, 2679–2685; g) A. Rahimi, A. Azarpira, H.
Kim, J. Ralph, S. S. Stahl, J. Am. Chem. Soc. 2013, 135, 6415–6418; h) R.
Liu, C. Dong, X. Liang, X. Wang, X. Hu, J. Org. Chem. 2005, 70, 729–731;
[25] C. Jin, L. Zhang, W. Su, Synlett 2011, 1435–1438.
Received: June 2, 2014
Published online on && &&, 0000
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FULL PAPER
One-pot oxidative esterification: A
wide variety of alcohols undergo transi-
tion-metal-free (in the presence of
oxone/2,2,6,6-tetramethyl-1-piperidiny-
loxy (TEMPO)/tetra-n-butylammonium
bromide (TBAB)) selective “cross”
esterification in moderate to excellent
yields (see Figure). The “self” esterifica-
tion process has however been ach-
ieved in the presence of Fe(OAc)2/2,6-
pyridinedicarboxylic acid (dipic) as the
active catalytic species under a similar
oxidizing environment.
&
Alcohol Esterification
R. Ray, R. D. Jana, M. Bhadra, D. Maiti,*
G. K. Lahiri*
&& – &&
Efficient and Simple Approaches
Towards Direct Oxidative Esterification
of Alcohols
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Chem. Eur. J. 2014, 20, 1 – 8
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8
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!