2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2- diazaphosphorine supported on polystyrene (PS-BEMP) as an efficient recoverable and reusable catalyst for the phenolysis of epoxides under solvent-free conditions

Article abstract of DOI:10.1002/adsc.201000375

2-tert-Butylimino-2-diethylamino-1,3-dimethylperhydro-1,3, 2-diazaphosphorine supported on polystyrene (PS-BEMP) is an efficient catalyst for the ring-opening of epoxides with phenols (1.0 equiv.). Excellent yields have been obtained and in most of the cases the final products have been isolated in pure form without any additional purification step. E-factors associated to this protocol are small and further improvements were obtained by setting a cyclic continuous-flow reactor operating under solvent-free conditions (SolFC) that allowed us to minimize waste and reduce the E-factor by 95% compared to batch conditions. In addition the representative synthesis of a 2,3-dihydrobenzo[1,4]dioxepin-5-one has been realized. Optimization of this process was achieved by setting up an automated multi-step continuous-flow reactor based on a phenolysis process and a subsequent lactonization by thermal treatment of the reaction mixture. 3-Phenoxymethyl-2,3-dihydrobenzo[e][1,4] dioxepin-5-one was isolated in pure form and on a multi-gram scale in a very satisfactory 86% overall yield and an E-factor of 1.47.

Full text of DOI:10.1002/adsc.201000375

FULL PAPERS
DOI: 10.1002/adsc.201000375
2-tert-Butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-
diazaphosphorine Supported on Polystyrene (PS-BEMP) as an
Efficient Recoverable and Reusable Catalyst for the Phenolysis
of Epoxides under Solvent-Free Conditions
Artis Zvagulis,a Simona Bonollo,a Daniela Lanari,a Ferdinando Pizzo,a
and Luigi Vaccaroa,*
a
Laboratory of Green Synthetic Organic Chemistry, CEMIN – Dipartimento di Chimica, Universitꢀ di Perugia, Via Elce di
Sotto 8, 06123 Perugia, Italy
Fax : (+39)-075-585-5560; e-mail: luigi@unipg.it
Received: May 14, 2010; Revised: August 3, 2010; Published online: September 28, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000375.
Abstract: 2-tert-Butylimino-2-diethylamino-1,3-dime-
ACHTUNGTREN[NGNU 1,4]dioxepin-5-one has been realized. Optimization
thylperhydro-1,3,2-diazaphosphorine supported on of this process was achieved by setting up an auto-
polystyrene (PS-BEMP) is an efficient catalyst for mated multi-step continuous-flow reactor based on a
the ring-opening of epoxides with phenols phenolysis process and a subsequent lactonization by
(1.0 equiv.). Excellent yields have been obtained and thermal treatment of the reaction mixture. 3-Phen-
in most of the cases the final products have been iso-
ACHUTGTNRNEUGoN xymethyl-2,3-dihydrobenzo[e]ACHUTNGTRENN[NGU 1,4]dioxepin-5-one
lated in pure form without any additional purifica- was isolated in pure form and on a multi-gram scale
tion step. E-factors associated to this protocol are in a very satisfactory 86% overall yield and an E-
small and further improvements were obtained by factor of 1.47.
setting a cyclic continuous-flow reactor operating
under solvent-free conditions (SolFC) that allowed Keywords: 2-tert-butylimino-2-diethylamino-1,3-di-
us to minimize waste and reduce the E-factor by methylperhydro-1,3,2-diazaphosphorine
(BEMP);
95% compared to batch conditions. In addition the continuous-flow chemistry; epoxides; green chemis-
representative synthesis of
a 2,3-dihydrobenzo- try; solvent-free conditions
Introduction
et al. by using a commercially available copper tetra-
fluoroborate salt.[5i] A recent related improvement has
Epoxides are valuable intermediates in organic syn- been reported by Baiker et al. by using a heterogene-
thesis.[1] Their use has been even more established ous, recoverable copper(II) salt.[5a]
after the definition of highly efficient methods for
Efficient methods for the streoselctive ring-opening
their preparation in optically enriched form.[2] The va- of epoxides by alcohols and phenols have been re-
riety of nucleophiles and the different promoters, re- ported,[6] including kinetic resolution of terminal ep-
action media and reaction conditions employed, make oxides and desymmetrization of meso-epoxides.[7]
the ring opening of epoxide an immensely studied or-
In the case of phenols as nucleophiles, basic condi-
tions have been generally employed and the use of a
ganic transformation.[1]
Among the different nucleophiles, alcohols and large quantity of reactant and/or promoting base is
phenols react very poorly with epoxides.[3] However, somehow mandatory. As an alternative, an excess of
this reaction is very important because it is the most the corresponding phenoxide salts is employed.[4a,5a,h,k]
direct access route for the preparation of b-alkyloxy
Our research program is committed to the optimi-
and b-aryloxy alcohols.[4] To overcome the limitation zation of synthetic procedures by employing eco-
related to the low reactivity of epoxides with alcohols, friendly reaction protocols, including the use of
only few well established procedures are known.[5] water,[8] solvent-free conditions (SolFC),[9] and sup-
Significant results have been obtained by Barluenga ported organocatalysts.[10]
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Table 1. Optimization of the base-catalyzed phenolysis of
phenyl glycidyl ether (1) and phenol (2a) under SolFC.
We have been paying much attention to the reactiv-
ity of epoxides and we have developed several proto-
cols for both their preparation and ring-opening by
carbo- and heteroatomic nucleophiles such as azido
ion, halides, amines and thiols, proving that the use of
alternative reaction media such as water[11] or
SolFC[12] is crucial for improving the efficiency of
these processes. In our previous works we had not ap-
plied our strategy to the definition of a protocol for Entry Catalyst[a]
the reaction of epoxides with phenols.
Time C [%][b] Yield
[h]
[%][c]
We have reported that polystyrene-supported 1,5,7-
triazabicycloACHTUNGTRENNUNG[4.4.0]dec-5-ene (PS-TBD) (10 mol%) is
1
3
50
98
>99
88
88
>99
79
12
–
–
99
–
–
–
–
–
–
2
3
4
5
6
7
8
9
PS-BEMP
15
20
20
3
8
3
a sufficiently strong base able to promote the addition
of phenol (2a) to styrene oxide 7 under SolFC.[10f] PS-
TBD was chosen by considering its higher basicity
among the commonly used nitrogen-containing organ-
ic bases (the pKa of the conjugate acid of PS-TBD is
>14 in water and 25.39 in MeCN).[13] Anyway, exten-
sion of the use of this base to other substrates gave
unsatisfactory results.
Recently, our attention has been focused on 2-tert-
butylimino-2-diethylamino-1,3-dimethylperhydro-
1,3,2-diazaphosphorine supported on polystyrene (PS-
BEMP), a very strong base (in MeCN the pKa is
27.63),[13] and a member of the class of Schwesingerꢂs
phosphazene bases, that have proved to be a widely
useful uncharged auxiliary base.[13]
PS-TBD
BEMP
MTBD[d]
PS-BEMP in MeCN
PS-BEMP in DCE or
DCM
PS-BEMP reused for
10 times
20
20
–
10
20
always
>99
98–99
[a]
[b]
PS=200–400 mesh polystyryl with 2% of divinylbenzene
as cross-linker.
Conversion to 3a measured by GLC analyses, the re-
maining material was the equimolar unreacted mixture
of 1 and 2a.
Isolated yield of the pure product 3a after filtering the
solid catalyst using 5 mLmmolÀ1 of EtOAc and after
vacuum evaporation of the latter (see Experimental Sec-
tion for further details).
[c]
[d]
By using a catalytic amount of PS-BEMP, we have
reported the nucleophilic addition of nitroalkanes to
a,b-unsaturated carbonyl compounds under solvent-
free conditions in batch conditions and also by using
a cyclic continuous-flow reactor,[10b] as well as the ad-
dition of carbon nucleophiles to epoxides.[11a]
7-Methyl-TBD.
In consideration of its strong basicity we have to that of non-supported MTBD (Table 1, entry 5 vs.
chosen PS-BEMP as catalyst to define a novel and ef- 7).
ficient procedure for the phenolysis of epoxides.
The influence of the reaction medium is dramatic.
Although we have used the best organic solvents for
swelling PS-BEMP,[13] the results obtained were com-
pletely unsatisfactory compared to SolFC. In fact, in
the presence of 2 mL/mmol of DCM or DCE no con-
Results and Discussion
In this article, we report our results in the use of PS- version to 3a was observed at all, while a poor 12%
BEMP as an efficient, recoverable and reusable solid 3a was formed when MeCN was used (Table 1, en-
basic catalyst able to promote the reaction of epox- tries 8 and 9).
ides (1, 4–7) with a variety of phenols (2a–k) under
solvent-free conditions.
According to our intention to define a simple and
efficient protocol with minimization of waste, we have
In preliminary studies, the efficiency of PS-BEMP used equimolar amounts of 1 and 2a. In all the cases
was compared to that of PS-TBD in the reaction of a conversion of 50% or more was reached in a rela-
phenyl glycidyl ether (1) and phenol (2a). The results tively short time (3 h), while completion of the reac-
are illustrated in Table 1.
tion requires a much longer time (Table 1, entries 1, 5,
At 608C, PS-BEMP showed a higher catalytic effi- and 7). This is just presumably due to the reduced
ciency than PS-TBD (Table 1, entry 3 vs. 4) and when concentration of 1a and 2a in the reaction mixture
PS-BEMP was used, a complete disappearance of the and cannot be attributed to a decreased efficiency of
reactants was observed after 20 h. Isolation of 3a was the catalyst, that was recovered and reused several
quantitative and no trace of its regioisomer coming times (at least 10) with no decrease of its efficiency
from the a-attack of 2a to the epoxide 1 was ob- allowing always the isolation of 1,3-diphenoxy-2-prop-
served. This result is also in agreement with the anol (3a) in almost quantitative yields (Table 1,
higher efficiency of non-supported BEMP compared entry 10).
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2-tert-Butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine Supported on Polystyrene
Table 3. Phenolysis of epoxides 4–7 catalyzed by 5 mol% of
PS-BEMP under SolFC at 608C.
To verify the application range of the use of PS-
BEMP in the phenolysis of epoxides, other substrates
were considered. The results of the reactions of equi-
molar amounts of epoxides 1, 4–7 and phenols 2a–j
are reported in the Table 2, Table 3, and Scheme 1.
Entry Epoxide
ArOH Time
Yield
[%][a]
a/b
[h]
ratio[b]
1
2
3
4
5
6
7
8
2a
2b
2d
2g
2a
2b
2d
2g
2a
2b
2d
24
60
60
38
96
34
40
40
96
34
38
7
38
45
60
60
20
60
94[c]
97
98
98
98
<1>99
<1>99
<1>99
<1>99
4/96
8/92
10/90
8/92
–
–
–
–
Table 2. Phenolysis of phenyl glycidyl ether (1) catalyzed by
5 mol% of PS-BEMP at 608C under SolFC.
96[d]
95[d]
96[d]
82[c]
85[c,d]
77[c,d]
95[d,e]
92[c,d]
94
9
10
11
12
13
14
15
16
17
18
Entry
1
Phenol
Time [h][a]
34
Yield [%][b]
99
2g
2a
2b
2d
–
68/32
80/20
84/16
67/33
58/42
78
69[c],
94[f]
89
2g
[a]
Overall isolated yield of the pure products (see Experi-
mental Section for further details).
Measured by GLC analyses; in the cases when a- and b-
isomers were formed they were isolated as pure products
by silica gel column chromatography.
Column chromatographic purification of the reaction
mixture was necessary.
Reaction performed at 808C.
2 equiv. of 6.
2 equiv. of 7.
2
18
99
[b]
[c]
3
4
5
6
40
28
70
20
99
99
87
99
[d]
[e]
[f]
An extension to alkyl alcohols was not investigated at
this stage considering that generally large amounts of
alcohols must be used to avoid a bis-product forma-
tion.
At 608C and by using 5 mol% of PS-BEMP, yields
were excellent in all the cases and reaction proceeded
to completeness in 18–70 h giving only the b-products
3b–j starting from the corresponding equimolar mix-
tures of 1a and 2b–j. Products were isolated in high
purity without any additional purification procedure.
The use of PS-BEMP was then extended to epoxide
4–7 and the representative phenols 2a, 2b, 2d, and 2g.
Allyl glycidyl ether (4) reacted satisfactorily giving
the corresponding products in very good yields and
complete b-regioselectivity. Also in the cases of
octene oxide (5) selected as a representative terminal
epoxide, cyclohexene oxide (6) as a commonly used
bicyclic epoxide, and styrene oxide (7) as a represen-
tative aryl-substituted epoxide, the corresponding
products were isolated in very high yields. Epoxides 5
and 6, were much less reactive than 1 and 4 and re-
quired a higher reaction temperature (up to 808C),
except in the case of phenol 2a where 608C was suffi-
cient to complete the ring opening process.
7
8
36
55
45
96
97
9
94[c]
[a]
Time for the complete conversion of 1 to 3.
Isolated yield of the pure product 3 (see Experimental
Section for further details).
[b]
[c]
Reaction performed at 808C.
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Scheme 1. Reaction of 1 with methyl salicylate (2k) leading to transesterification by-product 9 and 2,3-dihydrobenzo[e]-
ACHTUNGTRENNUNG[1,4]dioxepin-5-one 10.
As expected, in the case of 5 the regioselectivity of
PS-BEMP has proved to be an efficient catalyst for
the reaction favored the less substituted b-carbon, the phenolysis of epoxides under SolFC and the cor-
while the a-product was the major one in the case of responding b-aryloxy alcohols products were general-
7. All the a- and b-isomers were isolated as pure ly prepared in high yields and purity without further
products by silica gel column chromatography.
purification. In the presence of a reaction medium
In the reactions of 3-chlorophenol (2d) with cyclo- PS-BEMP is not efficient at all and therefore adop-
hexene oxide (6) and styrene oxide (7), formation of tion of SolFC was necessary.
a side product was observed when equimolar amounts
However, addition of an organic solvent (EtOAc)
of reactants were used. By-product 8 formed in the was still necessary at the end of the ring-opening pro-
case of epoxide 6 could be isolated only in mixture cess in order to isolate the products by filtering off
with 2d and its stereochemistry could not be assigned the PS-BEMP that is still fully efficient in further pro-
while its structure was confirmed by representative cesses.
1H NMR signals (see Supporting Information)
The use of equimolar amounts of reactants, the re-
(Figure 1). This product arises from the attack of the covery and reuse of the catalyst allowed the minimi-
zation of waste which results in a very low E-factor[14]
associated with our protocol.
As an example, in one of the best cases when 1 re-
acted with 2a (Table 1, entry 3), the E-factor is 18.6.
In the case of the reaction of 7 with 2d, when the use
of 2 equivalents of epoxide was necessary and the iso-
lated yield of the product was 94% (Table 3,
entry 17), the E-factor associated with this process
was 19.6, and this value becomes 19.1 if we consider
that the starting epoxide can be recovered in 93%
yield when the process was performed on a large
scale (100 mmol) (see Supporting Information).
Figure 1. By-product formed in the case of the reaction of 6
with 2d.
ring-opened product to another molecule of epoxide
In order to improve the efficiency of solvent-free
6. To avoid formation of this bis-product, we used 2 conditions, we have set-up a protocol by using a cyclic
or 4 equivalents of 2d, but the amount of 8 formed continuous-flow reactor operating under SolFC on a
was approximately identical or even bigger. Instead, 100-mmol scale in the case of the reaction of 4 with
the use of 2 equivalents of epoxide did not lead to the 2b (Figure 2, the thermostat box is not showed for
formation of 8 and the reaction was completed in 7 h. clarity).
Excess of cyclohexene oxide (6) was removed under
The reaction mixture at 608C was continuously
reduced pressure, to give the product in 99% yield. In pumped for 60 h through the catalytic amount of solid
addition, reactions of 6 and 7, were successfully per- PS-BEMP until conversion was complete. At this
formed on a 100-mmol scale and in this case it was point the pump is left to run in order to recover the
possible recover the excess of epoxide by distillation final product into the reservoir allowing 21.5 g (75%
in 93% yield.
yield) of 1-allyloxy-3-(4’-bromophenoxy)-propan-2-ol
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2-tert-Butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine Supported on Polystyrene
To satisfactorily achieve the preparation of 10, we
have investigated several reaction conditions for real-
izing the direct lactonization of 3k and by-product 9
by avoiding any additional protection/deprotection or
activation step that would reduce the overall efficien-
cy of the process making more difficult the scaling-up
procedures.
Lactonization and esterification reactions are im-
portant processes and have been largely investigated
to find mild catalysts and efficient conditions for
100% conversion of equimolecular amounts of car-
boxylic acids and alcohols.[16]
Unfortunately, in our case all the conditions used
led to decomposition processes (see Supporting Infor-
mation).
This somewhat correlates to our earlier observa-
tions in the preparation of the benzo[e]1,4-oxathiepin-
5-one ring, via lactonization of hydroxy-thiocarboxylic
acids.[12b] In this paper, we reported that thermal treat-
ment was the only efficient method for completing
this transformation and to avoid further manipulation
of a product coming from the epoxide ring-opening
by the corresponding thiol.[12b]
Therefore, thermal treatment was applied to 3k and
to 9 separately. After a long time (40 h) at 2008C only
60% was converted to 10 while 9 gave no reaction
(see Supporting Information).
Figure 2. Schematic diagram of the cyclic continuous-flow
reactor operating under SolFC.
(4b) to be isolated without using any organic solvent
Raising the temperature to 4508C for several mi-
at all. At this point, some EtOAc was added in three nutes led to partial conversion of both 3k and 9 to 10,
portions (3ꢃ6 mL)[15] to wash the catalyst and the re- proving that also the conversion of 9 to 10 was possi-
actor and recover additional 4.0 g of product 4b to ble. Prolonging this treatment for longer time
give an overall 96% yield after vacuum removal of (30 min) caused charring of the reaction mixture.
the organic solvent.
The optimal conditions were found for both sub-
In this case E-factor was further reduced from the strates at 3508C for 15 min. Under these conditions
16.2 obtained under batch conditions to 0.76 obtained
by using the SolFC reactor (a reduction of 95%).
The catalyst was completely recovered without
problems related to mass loss because it is kept in the
sealed glass column all the time.
We have then planned to exploit the catalytic effi-
ciency of PS-BEMP in the phenolysis of epoxide 1
under SolFC for the preparation of 2,3-
dihydrobenzo[e]ACHTUNGTRENNUNG[1,4]dioxepin-5-one 10 via the reac-
tion of 1 with methyl salicylate (2k) and subsequent
lactonization of 3k (see Scheme 1). In addition, to
reach this goal, we intended also to define a protocol
that should allow an easy scaling-up and E-factor
minimization.
The reaction conditions previously used (608C,
5 mol% of PS-BEMP, SolFC) proved to be efficient
also in the case of the phenolysis of 1 with 2k. How-
ever, under the reaction conditions, product 3k was
poorly converted to the desired 2,3-dihydrobenzo[e]-
ACHTUNGTRENNUNG[1,4]dioxepin-5-one 10 (18%), and in addition a trans-
esterification between two molecules of 3k led also to
the formation of by-product 9 (5%).
Scheme 2. Optimized lactonization of 3k and 9 to 2,3-
dihydrobenzo[e][1,4]dioxepin-5-one 10.
AHCTUNGTRENNUNG
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Artis Zvagulis et al.
FULL PAPERS
3k converted in 94% yield while for 9 conversion to used has a diameter of at least of 1.0–1.2 mm. In the
10 was quantitative (Scheme 2). case of smaller tubes, the solvent used for transferring
As alternative, we have also tried to cyclize 3k by the final portion of reaction mixture and washing the
using microwaves (250 W, 2008C) but after 15 min catalyst and the glass reactor, when suddenly heated
conversion to 10 was 58% and reduced over the time at 3508C causes a very accelerated flow reducing the
(1 h, 31% and 2 h, 22%), proving that this approach time of the thermal treatment and therefore resulting
was not suitable.
in the incomplete conversion to the desired 10. By
Finally, by treating the crude reaction mixture di- using a larger tube this phenomenon is reduced and
rectly coming from the reaction of 1 with 2k at 3508C reproducible results were obtained over three consec-
for 15 min, the complete conversion to 10 was utive experiments.
achieved
dihydrobenzo[e]
in 90% overall yield after purification over a silica gel EtOAc was used (3ꢃ4 mL)[15] to wash the silica. After
pad to remove some burned material. removal of the organic solvent under vacuum, the
We have then scaled-up and automated the prepa- pure 3-phenoxymethyl-2,3-dihydrobenzo[e]-
ration of 10 starting from 1 and 2k by coupling a [1,4]dioxepin-5-one (10) was isolated in an overall
cyclic continuous-flow reactor and a flow-through re- 86% yield.
and
pure
3-phenoxymethyl-2,3-
At this point, the highly concentrated solution of 10
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
actor as illustrated in Figure 3 (the thermostat box is
not showed for clarity).
The E-factor of this synthetic two-step large-scale
procedure for the preparation of 10 is a very good
At the end of the phenolysis of 1 with 2k, per- 1.47 (see Supporting Information). Further improve-
formed in the cyclic continuous-flow reactor, the re- ments of the E-factor can be obtained by recovery of
sulting reaction mixture was pumped to a 3-meterꢃ the EtOAc by distillation.
1.2 mm ø wire heated at 3508C at a constant flow of
0.5 mLminÀ1.[17]
To completely transfer the remaining reaction mix- Conclusions
ture of 3k and 9 from the phenolysis reactor to the
heating wire (ca 25% of the total), EtOAc was used In conclusion, we have reported that under SolFC PS-
(3ꢃ6 mL).[15]
BEMP is an efficient catalyst for the phenolysis of ep-
For the success of this large-scale two-step protocol, oxides 1, and 4–7 with phenols 2a-k. Excellent yields
the choice of the diameter of the tube used for the have been obtained and in most of the cases the final
wires is crucial. Several attempts were made but re- products have been isolated in pure form without any
producible results can be obtained only if the tube additional purification step.
The efficiency of this protocol is strictly related to
the use of SolFC that is necessary for the feasibility of
the reactions and also allows us to minimize the use
of organic solvent. As a consequence waste associated
with the batch protocol is very little and E-factors are
significantly small. Further improvements were ob-
tained by setting up a cyclic continuous-flow reactor
operating under SolFC that allowed us to further
reduce the E-factor by 95% compared to batch condi-
tions.
Finally, we have exploited the phenolysis protocol
by realizing the synthesis of 2,3-dihydrobenzo
[1,4]dioxepin-5-one 10. Optimization of this process
was achieved by setting up an automated multistep
continuous-flow reactor based on the phenolysis of 1
with 2k and subsequent lactonization by thermal
treatment of the reaction mixture. 3-Phenoxymethyl-
2,3-dihydrobenzo[e]ACTHNUGRTENUNG[1,4]dioxepin-5-one (10) was iso-
lated in pure form and on a multigram scale in a very
satisfactory 86% overall yield. The E-factor of 1.47
associated with this procedure makes the synthesis of
this heterocycle highly environmentally efficient.
Figure 3. Schematic diagram of the continuos-flow/flow-
through reactor for the automated synthesis of 2,3-
dihydrobenzo[e]
ACHTUNGTRENNUNG
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2-tert-Butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine Supported on Polystyrene
[3] J. G. Smith, Synthesis 1984, 629–656.
[4] a) M. A. Brimble, Y.-C. Liu ACTHNUGRTNEUNG(William), M. Trzoss, Syn-
Experimental Section
thesis 2007, 1392–1402; b) C. Franchini, A. Carocci, A.
Catalano, M. M. Cavalluzzi, F. Corbo, G. Lentini, A.
Scilimati, P. Tortorella, D. Conte Camerino, A.
De Luca, J. Med. Chem. 2003, 46, 5238–5248; c) D. E.
Carpenter, R. J. Imbordino, M. T. Maloney, J. A. Moe-
slein, M. R. Reeder, A. Scott, Org. Process Res. Dev.
2002, 6, 721–728; d) P. A. Procopiou, A. C. Brodie,
M. J. Deal, D. F. Hayman, Tetrahedron Lett. 1993, 34,
7483–7486.
General Remarks
All chemicals were purchased and used without any further
purification. All 1H NMR and 13C NMR spectra were re-
corded at 400 MHz and 100.6 MHz, respectively, using a
convenient deuterated solvent (reported in the characteriza-
tion charts) and the residual peak as internal standard, or
TMS in the case of CDCl3. Column chromatographies were
performed by using silica gel 230–400 mesh and eluting as
reported in the following characterization charts. PS-BEMP
was purchased from Aldrich.
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Compounds 3a, b,[5f] 3d,[18] 3e,[19] 3f, g,[5f] 4a,[20] 4b,[19] 5a (b-
product),[21] 5b (b-product),[21] 6a, b,[22] 6g,[22] 7a (a- and b-
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pounds, while compounds 3c, 3h, 3i, 3k, 4d, 4g, 5a (a-prod-
uct), 5b (a-product), 5d (a- and b-products), 5g (a- and b-
products), 6d, 7b (a- and b-products), 7d (a- and b-prod-
ucts), 8, 9, and 10 are new compounds.
Characterization data and copies of the H and 13C NMR
spectra for all compounds 3a–k, 5a–d, 6a–d, 7a–d, and 8–10
are given in the Supporting Information.
1
Representative Batch Experimental Procedure
In a screw-capped vial equipped with a magnetic stirrer PS-
BEMP (0.048 g, 0.1 mmol, 2.1 mmol/g), 4-bromophenol (2b)
(0.346 g, 2.0 mmol) and phenyl glycidyl ether (1) (0.300 g,
2.0 mmol) were consecutively added and the resulting mix-
ture was left under stirring at 608C. After 34 h EtOAc
(2 mL) was added and the reaction mixture filtered. The cat-
alyst was washed using additional 4ꢃ2 mL of EtOAc. Or-
ganic layers were collected and solvent was removed under
vacuum to give 1-(4-bromophenoxy)-3-phenoxypropan-2-ol
(3b) as a white solid; yield: 0.641 g (99%).
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Acknowledgements
We gratefully acknowledge the Ministero dell’Istruzione, del-
l’Universitꢀ e della Ricerca (MIUR) within the projects PRIN
2008 and “Firb-Futuro in Ricerca” and the Universitꢀ degli
Studi di Perugia for financial support.
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Adv. Synth. Catal. 2010, 352, 2489 – 2496