Carbon tetrabromide/sodium triphenylphosphine-m-sulfonate (TPPMS) as an efficient and easily recoverable catalyst for acetalization and tetrahydropyranylation reactions

Article abstract of DOI:10.1002/adsc.200900102

A solid complex, conveniently prepared from carbon tetrabromide and sodium triphenylphos-phine-m-sulfonate (TPPMS), can be used as an easily recoverable catalyst for the selective acetalization of aldehydes and tetrahydropyranylation of alcohols. The catalyst can be recovered by simple pre-cipitation with ether and can be reused at least 7 times without loss of catalytic activity.

Full text of DOI:10.1002/adsc.200900102

FULL PAPERS
DOI: 10.1002/adsc.200900102
Carbon Tetrabromide/Sodium Triphenylphosphine-m-sulfonate
(TPPMS) as an Efficient and Easily Recoverable Catalyst for
Acetalization and Tetrahydropyranylation Reactions
Congde Huoa and Tak Hang Chana,*
a
Department of Chemistry, McGill University, Montreal, Quebec, Canada H3A2K6
Fax : (+1)-514-398-3797; e-mail: tak-hang.chan@macgill.ca
Received: February 13, 2009; Published online: July 16, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900102.
Abstract: A solid complex, conveniently prepared cipitation with ether and can be reused at least 7
from carbon tetrabromide and sodium triphenylphos- times without loss of catalytic activity.
phine-m-sulfonate (TPPMS), can be used as an
easily recoverable catalyst for the selective acetaliza- Keywords: acetalization; carbon tetrabromide; orga-
tion of aldehydes and tetrahydropyranylation of al- nocatalysts; sodium triphenylphosphine-m-sulfonate;
cohols. The catalyst can be recovered by simple pre- tetrahydropyranylation
Introduction
ture usually require chromatography.[1–10] In here, we
describe a catalytic system of CBr4 which is stable,
Carbon tetrabromide (CBr4) has been used as organo- functions under mild conditions, is easily recoverable
catalyst for a variety of organic transformations. For from the reaction mixture, and reusable for acetaliza-
example, it catalyzes the hydrolysis of acetals in ace- tion and tetrahydropyranylation reactions.
tonitrile/water solution,[1] the hydrolysis of tetrahydro-
pyranyl ethers in methanol,[2] the cleavage of trityl
ethers in methanol,[3] the deprotection of trialkylsilyl Results and Discussion
esters,[4] as well as selectively b-(trimethylsilyl)ethoxy-
methyl ethers.[5] It also serves as the catalyst for Since CBr4 was able to catalyze the hydrolysis of ace-
esterification[4,6,7] and epoxide ring opening.[8] More tals,[1] we reasoned that it can also be used for the for-
recently, carbon tetrabromide has been found to me- mation of acetals from aldehydes and alcohols. Using
diate the formation of carbon-sulfur bond[9] and thio- p-nitrobenzaldehyde (1a) in methanol at 258C for
ureas.[10] As a catalyst, CBr4 offers the advantages that 12 h as the standard conditions, the catalytic forma-
the reaction conditions are generally mild, and the re- tion of the acetal 2a (Scheme 1) with CBr4 was indeed
actions are often chemo-[11] as well as regioselective.[8] found to be effective, giving a yield of 88% (Table 1,
On the other hand, CBr4 is an irritant and a toxic sub- entry 1). It is more effective than the commonly used
stance (IVN-MUS LD50: 56 mgkgÀ1) and may cause p-toluenesulfonic acid (PTSA) which gave 2a in 67%
damage to liver and kidney.[12] Its release into the en- yield under the same conditions (entry 2). Interesting-
vironment would be hazardous. Because of the ready ly, the use of triphenylphosphine (TPP)/CBr4, a re-
solubility of CBr4 in many organic solvents, the sepa- agent usually used for the Corey–Fuchs[13] and
ration and recovery of CBr4 from the reaction mix-
Scheme 1. Acetalization of p-nitrobenzaldehyde with methanol.
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Congde Huo and Tak Hang Chan
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Table 1. Acetalization of p-nitrobenzaldehyde according to
Scheme 1.
the possibility of using TPPMS/CBr4 as a catalyst for
the acetalization reaction.
A mixture of TPPMS and carbon tetrabromide (1:1
molar ratio) was stirred at room temperature in meth-
anol for several hours, then the reaction mixture was
concentrated and ether was added to precipitate the
TPPMS/CBr4 complex (3) as a white solid. As we can
see from Table 1, the complex 3 was able to catalyze
the acetalization effectively giving >95% yield of 2a
(entry 4). The catalytic activity was not due to
TPPMS, as the compound itself or its oxidation prod-
uct TPPMSO, was devoid of activity (entries 5 and 6).
Since CBr4 may react with methanol to give HBr, we
examined the catalytic activities of TPPMS/HBr and
TPPMSO/HBr as well. Both were found to be active
but not as efficient as 3 (compare entries 7 and 8 with
entry 4). Finally, we also examined the complex
Entry
Catalyst used
Yield [%]of 2a[a]
1
2
3
4
5
6
7
8
9
CBr4
PTSA
TPP/CBr4
TPPMS/CBr4 (3)
TPPMS
88
67
90
>95
0
TPPMSO
0
TPPMS/HBr
TPPMSO/HBr
TPPMSO/CBr4
60
33
86
[a]
1
The yield was based on the H NMR spectra of crude re-
action mixtures.
Appel[14] reactions, was equally effective in catalyzing TPPMSO/CBr4 (4) and found that it also had catalytic
the acetalization (entry 3).
activity (entry 9) but again not as effective as 3.
A useful property of the complex 3 is that it is solu-
We have recently developed the use sodium triphe-
nylphosphine-m-sulfonate (TPPMS) as a replacement ble in relatively polar organic solvents such as metha-
of triphenylphosphine in the Wittig reaction.[15] The nol but can be easily and quantitatively recovered
advantage of using TPPMS is that it and its oxidation from the reaction mixture by simply adding a non-
product,
sodium
triphenylphosphine-m-sulfonate polar organic solvent such as ether. This is illustrated
oxide (TPPMSO), can be easily separated and recov- in Figure 1. In Tube A, complex 3 was dissolved in
ered from the reaction mixture by precipitation with methanol (sudan red 7B was added to aid viewing).
a non-polar solvent, without the need for tedious By adding ether to the solution, 3 precipitated from
chromatography as is usually required for the removal the solution (Tube B). After filtration, the solid 3
of triphenylphosphine oxide. We therefore examined (Tube D) can be separated from the filtrate (Tube C)
Figure 1. Recovery of complex 3. Tube A) complex 3 (50 mg), sudan red 7B (3 mg) and MeOH (1 mL); Tube B) addition of
Et2O (3 mL); Tube C) filtrate obtained from filtration of B; Tube D) recovered 3 (47 mg) after washing with Et2O (3ꢁ5 mL)
and drying.
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Carbon Tetrabromide/Sodium Triphenylphosphine-m-sulfonate (TPPMS)
FULL PAPERS
Table 2. Recycle of 3 for acetalization of p-nitrobenzalde-
Table 4. Acetalization of benzaldehydes with various alco-
hols using 3 as catalyst.
hyde according to Scheme 1.[a]
Cycle
1
2
3
4
5
6
7
Entry ROH
Product
Yield [%]
96
Yield
>95
>95
93
90
93
93
92
1
2
3
EtOH
[a]
1
The yield was based on the H NMR spectra of crude re-
action mixtures.
i-PrOH/DCM
BnOH/DCM
91
95
Table 3. Acetalization of various aldehydes with methanol.
Entry
Aldehyde (1)
Isolated yield [%] of 2
4
(CH2OH)2/DCM
95
1
2
3
p-nitrobenzaldehyde 1a
m-nitrobenzaldehyde 1b
o-nitrobenzaldehyde 1c
98
96
96
5
(CH2OH)2/DCM
82[a]
4
90
[a]
608C.
5
91
at room temperature overnight. In the case of p-me-
thoxybenzaldehyde, the lower yield (entry 12) ob-
tained was probably due to the equilibrium influenced
by the methoxy substituent. Indeed, by adding a de-
hydrating agent (MgSO4) to the reaction mixture, a
higher yield (77%) of the acetal was obtained. Ali-
phatic aldehydes gave good yields of the correspond-
ing acetals even without the need of a dehydrating
agent. The ester function was stable to the acetaliza-
tion conditions. Thus, aldehydes 1e (entry 5) was effi-
ciently acetalized. For aldehyde 1g (entry 7), the
methyl carbonate function was stable to the acetaliza-
tion conditions but a lower amount of catalyst
(2 mol%) was used, otherwise, cleavage of the car-
bonate function was observed. Interestingly, the tert-
butoxycarbonyl function also survived the acid condi-
tions at 2 mol% catalyst (entry 6). As expected,[4] tri-
alkylsilyl ethers such as t-butyldimethylsilyl ether
were cleaved under the reaction conditions. On the
other hand, the more bulky tert-butyldiphenylsiloxy
group was relatively stable (see below).
6
90[a]
7
8
81[a]
91
9
89
84
10
benzaldehyde 1j
11
12
13
78
47 (77)
93
92
14
[a]
2 mol% catalyst was used.
Acetalizations with alcohols other than methanol
were also catalyzed by compound 3 (Table 4). In the
and recovered quantitatively. In the acetalization re- case of higher boiling alcohols, a stoichiometric
action, the separation and recovery of the catalyst 3 amount of the alcohol was used and the reaction was
was therefore simply carried out by precipitation with conducted in dichloromethane as the solvent (Table 4,
ether after completion of the reaction (see Experi- entries 2–5). The product acetals were formed in good
mental Section). The recovered catalyst 3 can be yields. In the case of p-tert-butyldiphenylsiloxybenzal-
reused without loss of catalytic activity. We demon- dehyde (entry 5), the acetal 2s was formed in good
strated this with the acetalization of p-nitrobenzalde- yield without cleavage of the silyl group. The catalytic
hyde with methanol using recovered 3 for seven system 3 showed remarkable chemoselectivity in ace-
cycles without diminished yield (Table 2).
talizing aldehydes only. Simple ketones such as benzo-
The complex 3 was able to catalyze the acetaliza- phenone, acetophenone and cyclohexanone were
tion of both aryl and aliphatic aldehydes with metha- completely unreactive with methanol and 5 mol% of
nol as indicated in Table 3. The reaction conditions 3 and no acetal was observed even after 48 h at room
are usually quite mild, simply stirring of the solution temperature or reflux for 8 h. Thus, 4-acetylbenzalde-
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Congde Huo and Tak Hang Chan
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Tetrahydropyranylation is widely used to protect al-
cohols because they are stable enough to strong basic
media, oxidative conditions, reduction with hydrides,
and many reactive organometallic reagents such as
Grignard reagents or lithium alkyls. On the other
hand, tetrahydropyranyl ethers are easily deprotected
under acidic conditions. The complex 3 was shown to
be an effective catalyst for the tetrahydropyranylation
of various alcohols at room temperature in dichloro-
methane (Scheme 3 and Table 5). As shown in
Table 5, primary, secondary, benzylic, allylic alcohols
and phenols with different substituents were convert-
Scheme 2. Selective acetalization.
Scheme 3. Tetrahydropyanylation of alcohols.
hyde was selectively acetalized with methanol using ed to the corresponding THP ethers with good yields.
5 mol% of 3 to give the acetal 2t in quantitative yield The tertiary trityl alcohol was also converted to the
(Scheme 2). Only a few of the acetalization methods THP ether in good yield (entry 12). The mild reaction
reported the chemoselective protection of aldehydes conditions did not isomerize double bonds during the
in the presence of ketone function.[16,17j]
reaction (entries 9 and 13). The separation and recov-
ery of catalyst 3 was conveniently achieved with the
precipitation/filtration sequence initiated by the addi-
tion of diethyl ether.
Table 5. Tetrahydropyranylation of alcohols according to
Scheme 3.
The exact structure of complex 3 has not been
firmly established. In the case of triphenylphosphine/
CBr4, it was generally assumed that a phosphonium
intermediate was formed, involving the cleavage of
Entry
ROH used
Yield [%]
1
2
3
4-nitrophenol
4-bromophenol
phenol
89
91
93
94
87
92
94
95
95
84
91
80
[13,14]
À
the C Br bond.
Using that as analogy, a plausible
mechanism for the catalytic action of 3 is illustrated
in Scheme 4. The aldehyde is activated by coordina-
tion with the phosphonium intermediate 3 to give the
pentacovalent intermediate 5. Recently, phosphonium
salts have been proposed as novel metal-free Lewis
acid catalysts by virtue of the hypervalent intereaction
through the formation of pentacoordinate intermedi-
ates.[17] Addition of alcohol to 5 gives the hemiacetals
6. Dissociation of 6 gives the cationic intermediate 7
and the phosphorus compound 8. Reaction of 7 with
another alcohol gives the acetal 2 with the release of
4
4-cresol
5
2-naphthol
6
1-hexanol
7
1-octanol
8
9
10
11
12
3-phenyl-1-propanol
cinnamyl alcohol
2-octanol
cyclohexanol
trityl alcohol
13
90
Scheme 4. Mechanism for the catalyzed acetalization reaction by 3.
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Carbon Tetrabromide/Sodium Triphenylphosphine-m-sulfonate (TPPMS)
FULL PAPERS
(b): In the case of high boiling alcohols, the TPPMS/CBr4
complex (5 mol%) and the appropriate aldehyde
a proton whereas 8 acquires a proton to regenerate 3.
In the catalytic cycle, aldehyde is converted to the
acetal with the formation of a water molecule. A simi-
lar mechanism can be suggested for the tetrahydro-
pyranylation of alcohols.
3
(0.2 mmol) were added to dichloromethane (1 mL). The ap-
propriate alcohol (0.24 mmol, 1.2 equiv.) was added and the
reaction mixture was stirred at room temperature overnight.
The mixture was worked up in the same manner as above to
recover 3 and to obtain the acetal.
Conclusions
Recycling Study
The catalyst 3 (5 mol%) and p-nitrobenzaldehyde (30 mg,
0.2 mmol) was added to methanol (1 mL). The reaction mix-
ture was stirred at room temperature for 12 h. Ether (3 mL)
was added and the mixture was filtered. The solid recovered
was dissolved in methanol (1 mL) for the next round of ace-
talization. Seven cycles were done and the yields were 95%,
In conclusion, we have demonstrated that the
TPPMS/CBr4 complex 3 is a highly efficient catalyst
for the synthesis of both cyclic and acyclic acetals
from a range of aldehydes in high yields. The synthe-
sis proceeds at room temperature without the require-
ment of inert or anhydrous reaction conditions. The
catalyst 3 is stable and can be kept readily. It is easily
separable from the substrate and product and can be
recovered and reused without loss of catalytic activity
for at least 7 cycles. The catalyst also works for the
tetrahydropyranylation of various alcohols.
1
95%, 93%, 90%, 93%, 93%, 92% based on H NMR spec-
tra.
Typical Procedure for Tetrahydropyranylation
To a solution of 3,4-dihydro-2H-pyran (0.3 mmol) and the
appropriate alcohols or phenols (0.2 mmol) in DCM (1 mL),
the TPPMS/CBr4 complex 3 (5 mol%) was added. The mix-
ture was stirred overnight at room temperature. To the mix-
ture, ether (3 mL) was added. The TPPMS/CBr4 complex 3
was recovered by filtration. The liquid filtrate was evaporat-
ed to give the corresponding products, usually in good
purity. Column chromatography may be necessary in some
case to give pure product.
Experimental Section
Preparation of the TPPMS/CBr4 Complex 3
A mixture of TPPMS (728 mg, 2 mmol) and carbon tetra-
bromide (663 mg, 2 mmol) was stirred at room temperature
in methanol (10 mL). After 4 h, the reaction mixture was
concentrated and ether was added. After filtration, the
TPPMS/CBr4 complex 3 was obtained as a white solid;
yield: 1 g (70%). 1H NMR (400 MHz, CD3OD): d=8.10–
8.07 (m, 2H), 7.82–7.77 (m, 1H), 7.69–7.63 (m, 7H), 7.58–
7.54 (m, 4H); 31P NMR (81 MHz, CD3OD): d=32.7 (s, 1P);
13C NMR (100 MHz, CD3OD): d=146.1, 146.0, 133.5, 133.4,
132.9, 132.8, 132.8, 132.0, 131.9, 131.8, 131.5, 130.4, 130.0,
129.9, 129.3, 129.2, 129.1, 129.0, 129.0, 128.9.
The acetals and the tetrahydropyranyl ethers are all
known compounds: They were properly characterized and
found to be in agreement with literature reports.[18]
Acknowledgements
We thank the Natural Science and Engineering Research
Council (NSERC) of Canada for financial support.
Standard Conditions to Assess the Catalytic Activity
of Various Catalysts According to Scheme 1 (Table 1)
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