Crown Ethers as New Catalysts in the Highly Regioselective Halogenative Cleavage of Epoxides with Elemental Halogen

Article abstract of DOI:10.1021/jo971453y

The regioselective ring opening halogenation of some epoxides using elemental iodine and bromine in the presence of a series of new synthetic macrocycle diamides and also dibenzo-18-crown -6, 18-crown-6, and aza-18-crown-6 has been studied. The epoxides were subject to cleavage by elemental halogen (I₂ and Br₂) in the presence of these catalysts under mild reaction conditions in various aprotic solvents. In this study, reagents and conditions have been discovered with which the individual halohydrins can be synthesized in high yield and with more than 95% regioselectivity. The results can be discussed in terms of a four-step mechanism: (1) formation of a charge-transfer complex between catalyst and halogen, (2) release of halogen nucleophile from the complex, (3) reaction of the active nucleophile at the less sterically-hindered site in the epoxide, and (4) regeneration of catalyst. The major advantages of this method are high regioselectivity, simple regeneration of catalyst and its reuse through several cycles without a decrease in activity, and ease of workup of the reaction.

Full text of DOI:10.1021/jo971453y

J . Org. Chem. 1998, 63, 1455-1461
1455
Cr ow n Eth er s a s New Ca ta lysts in th e High ly Regioselective
Ha logen a tive Clea va ge of Ep oxid es w ith Elem en ta l Ha logen
Hashem Sharghi,* Ahmad Reza Massah, Hossein Eshghi, and Khodabakhsh Niknam
Department of Chemistry, Shiraz University, Shiraz 71454, Iran
Received August 5, 1997
The regioselective ring opening halogenation of some epoxides using elemental iodine and bromine
in the presence of a series of new synthetic macrocycle diamides and also dibenzo-18-crown -6,
18-crown-6, and aza-18-crown-6 has been studied. The epoxides were subject to cleavage by
elemental halogen (I2 and Br2) in the presence of these catalysts under mild reaction conditions in
various aprotic solvents. In this study, reagents and conditions have been discovered with which
the individual halohydrins can be synthesized in high yield and with more than 95% regioselectivity.
The results can be discussed in terms of a four-step mechanism: (1) formation of a charge-transfer
complex between catalyst and halogen, (2) release of halogen nucleophile from the complex, (3)
reaction of the active nucleophile at the less sterically-hindered site in the epoxide, and (4)
regeneration of catalyst. The major advantages of this method are high regioselectivity, simple
regeneration of catalyst and its reuse through several cycles without a decrease in activity, and
ease of workup of the reaction.
In tr od u ction
relatively long reaction times.4c,11,14-16 Recently, it has
been found that epoxides can be converted into iodohy-
drins and bromohydrins by means of elemental iodine
and bromine,17 but this method has some limitations such
as low yield and regioselectivity with long reaction times
and formation of acetonide byproducts in addition to the
expected iodoadduct in acetone solution. Furthermore,
iodination does not occur in CH2Cl2, CHCl3, C6H6, CH3CN,
and THF solvents.
In conjuction with ongoing work in our laboratory on
the synthesis and complex formation of macrocyclic
compounds with natural molecules such as iodine and
bromine,18-20 we found that these compounds efficiently
catalyzed the addition of elemental iodine and bromine
to epoxides. Seven new macrocyclic diamides as well as
dibenzo-18-crown-6, 18-crown-6, and aza-18-crown-6 were
selected as catalysts in these reactions.
There is a continued interest in the regioselective ring
opening of oxiranes to the corresponding vicinal halohy-
drins. Although a variety of new and mild procedures
to effect this transformation have been reported, most
of them have some limitations.1 Methods based upon
hydrogen halides are not considered appropriate because
of the formation of some unwanted byproducts and low
regioselectivity.2 Ring opening of unsymmetrically sub-
stituted oxiranes with chlorosilanes,3 haloborane re-
agents,4,5 Br2/PPh3,6 Me3SiBr,7 Py‚HCl,8 Lewis acid metal
12
halides,9,10 X2Ti(O-i-pr),11 Li2NBr4 and n-Bu4N+Br-/
Mg(NO3)213 have been reported. However, these methods
are not always fully satisfactory and suffer from disad-
vantages such as acidity, handling and in situ prepara-
tion of reagent, noncatalytic nature of the reagents, and
Here we report the synthesis of these novel macrocyclic
diamides and the results of the reactions of some epoxides
with elemental iodine and bromine in the presence of
catalytic amounts of these macrocyclic compounds.
(1) (a) Fieser, M.; Fieser, L. F. Reagents for Organic Synthesis,
Smith, J . G.; Fieser, M.; J ohn Wiley New York, 1990. (b) Bonini, C.;
Righi, G. Synthesis 1994, 225-238. (c) Larock, R. C. Comprehensive
Organic Transformations; VCH Publishers: New York, 1989; 508-
509(2. ) (a) Stewart, C.a.; Varder Werf, C. A. J . Am. Chem. Soc. 1954,
76, 1259. (b) Boguslavskaya, L. S. Russ. Chem. Soc. Rev. 1972, 41,
740. (c) Owen, L. N.; Saharia, G. S. J . Chem. Soc. 1953, 2582.
(3) Andrews, G. C.; Grawford, T. C.; Contilio, L. G., J r. Tetrahedron
Lett. 1981, 22, 3803.
Resu lts
(4) (a) Guindon, Y.; Therien, M.; Girard, Y.; Yoakim, C. J . Org.
Chem. 1987, 52, 1680. (b) J oshi, N. N.; Srebnik, M.; Brown, H. C. J .
Am. Chem. Soc. 1988, 110, 6246. (c) Bell, T. W.; Ciaccio, J . A.
Tetrahedron Lett. 1986, 27(7), 827.
(5) Mandal, A. K.; Soni, N. R.; Ratnam, K. R. Synthesis 1985, 274.
(6) Palumbo, G.; Ferreri, C.; Caputo, R. Tetrahedron Lett. 1983,
24(12), 1307.
(A) P r ep a r a tion of Ca ta lyst. Although macrocyclic
amides were originally regarded as intermediated to aza
crowns, only a few procedures have been developed for
their preparation. Among these, carboxylic acid deriva-
(7) Kricheldorf, H. R.; Morber, G.; Regel, W. Synthesis 1981, 383.
(8) Loreto, M. A.; Pellacani, L.; Tardella, P. A. Synth. Commun.
1981, 11, 287.
(9) (a) Eisch, J . J .; Liu, Z. R.; Ma, X.; Zheng, G. X. J . Org. Chem.
1992, 57, 5140. (b) Iranpoor, N.; Salehi, P. Synth. Commun. 1997, in
press. (c) Shimizu, M.; Yoshida, A.; Tamotsu, F. Synlett 1992, 204.
(10) (a) Eisch , J . J .; Liu, Z. R.; Singh, M. J . Org. Chem. 1992, 57,
1618. (b) Bonini, C.; Righi, G.; Sotgiu, G. Ibid. 1991, 56, 6206.
(11) Alvarez, E.; Nunez, M. T.; Martin, V. S. J . Org. Chem. 1990,
55, 3429.
(14) (a) Bajwa, J . S.; Anderson, R. C. Tetrahedron Lett. 1991, 32(26),
3021. (b) Bonini, C.; Giuliano, C.; Righi, G.; Rossi, L. Synth. Commun.
1992, 22(13), 1863.
(15) Chini, M.; Crotti, P.; Gardelli, C.; Macchia, F. Tetrahedron 1992,
48(18), 3805.
(16) Gao, L. X.; Saitoh, H.; Feng, F.; Murai, A. Chem. Lett. 1991,
1787.
(17) Konaklieva, M. I.; Dahi, M. L.; Turos, E. Tetrahedron Lett. 1992,
33(47), 7093.
(18) Sharghi, H.; Eshghi, H. Tetrahedron 1995, 51, 913.
(19) Gangali, M. R.; Eshghi, H.; Sharghi, H.; Shamsipour, M. J .
Electroanal. Chem. 1996, 405, 177.
(12) Dawe, R. D.; Molinski, T. F.; Turner. J . V. Tetrahedron Lett.
1984, 25(19), 2061.
(13) Suh, Y. G.; Koo, B. A.; Ko, J . A.; Cho, Y. S. Chem. Lett. 1993,
1907.
(20) Massah, A. R. Ph.D. Thesis, Shiraz University , Shiraz, Iran,
1997.
S0022-3263(97)01453-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 02/14/1998

1456 J . Org. Chem., Vol. 63, No. 5, 1998
Sharghi et al.
Ta ble 1. Ha logen a tive Clea va ge of Styr en e Oxid e in th e
P r esen ce of Va r iou s Ma cr ocyclic Com p ou n d s in CH2Cl2
a t 25 °C
Sch em e 1
time (h)
yielda (%)
catalyst
bromi-
iodi-
bromi-
iodi-
entry
(0.1 mol)
nation
nation
nation
nation
1
2
3
4
5
6
7
8
9
7
8
9
10
11
12
13
14
15
16
immed
immed
0.25
0.3
0.5
0.5
0.25
0.25
0.4
0.7
1
immed
immed
24 (20)b
18 (13)b
24
24
3.5
2
24
>95
>95
90
88
92
>95
>95
50
65
50
90
90
90
80
90
>95
>95
85
10
11
24
80
50
several
31d
0d
daysc
GC yield. Under reflux. c In the presence of excess of iodine.
Data taken from ref 17.
a
b
d
rides 5 and 6. Cyclization was carried out with fast
addition of diamine in CH2Cl2 (or a mixture of DMF/
CH2Cl2) into a solution of dicarboxylic acid dichloride in
CH2Cl2 over 5 s with vigorous stirring. Then, the mixture
was stirred at room temperature for 20 min to give
macrocyclic diamides in 69-80% yields.
Other crown ethers that were used as catalysts in
halogenation of epoxides are shown:
(B) Ha logen a tion of Ep oxid es. Epoxides of conve-
nient volatility to allow GC analysis were chosen for
study. As catalysts, some macrocyclic diamides that were
synthesized according to Scheme 1 were used. Also,
dibenzo-18-crown-6 (14), 18-crown-6 (15), and aza-18-
crown-6 (16) were selected to represent some common
crown ether catalysts. The results of the reactions of
styrene oxide with elemental iodine and bromine in the
presence of the above catalysts are summarized in Table
1. In each case, cleavage of the epoxide ring occurs and,
upon thiosulfate workup, the corresponding iodohydrin
and bromohydrin were obtained. The catalysts were
easily recovered and could be reused several times. In
comparison, the cleavage behavior of styrene oxide with
elemental iodine and bromine in the absence of catalyst
is given in entry 11.
As is shown in Table 1, yields of both iodination and
bromination with this new methodology are quite good.
Catalysts 7 and 8 are the most effective, and reactions
occur instantaneously in the presence of these catalysts
(Table 1, entries 1 and 2). In the presence of other
catalysts, the reaction times for bromination and iodi-
nation at room temperature are in the range 0.25-0.7
and 3.5-24 h, respectively. However, iodination of
styrene oxide with an excess of elemental iodine in the
absence of catalyst did not occur even under reflux and
extension of reaction time to several days, and unreacted
styrene oxide was completely recovered. In addition, the
yield of bromination reactions is very low in the absence
of catalysts.
tives, such as malonic and R,ω-dicarboxylic acid esters,21
labile diacid dichlorides,22,23 and bis(R-chloroamide)
compounds,24-26 were allowed to react with various
diamines under high dilution or for long reaction periods.
In previous studies,18 we reported a new efficient syn-
thesis of macrocyclic diamides. No high dilution tech-
nique was required in this method. We applied this
approach to the synthesis of dilactams 7-13 (Scheme 1).
Methyl salicylate was reacted with diethyleneglycol
dibromide or triethyleneglycol dibromide in acetone in
the presence of potassium carbonate to give diesters 1
and 2 in 90 and 92% yields, respectively. Dicarboxylic
acids 3 and 4 were obtained in quantitative yield by
saponification of the corresponding diester followed by
acid treatment. Treatment of 3 and 4 with thionyl
chloride gave 90-95% yield of dicarboxylic acid dichlo-
(21) (a) Tabushi, I.; Taniguchi, Y.; Kato, H. Tetrahedron Lett. 1977,
1049. (b) Tabushi, I.; Okino, H.; Kuroda, Y. Ibid. 1976, 4339.
(22) (a) Petranek, J .; Ryba, O. Collect. Czech. Chem. Commun. 1980,
45, 1567. (b) Petranek, J .; Ryba, O. Ibid. 1983, 48, 1945.
(23) (a) Pellisard, D.; Louis, R. Tetrahedron Lett. 1972, 45, 4589.
(b) Dietrich, B.; Lehn, J . M.; Sauvage, J . P.; Blanzat, J . Tetrahedron
1973, 29, 1629.
(24) Krakowiak, K. E.; Bradshaw, J . S.; Izatt, R. M. J . Org. Chem.
1990, 55, 3364.
(25) Bradshaw, J . S.; Krakowiak, K. E.; Izatt, R. M.; Zamecka-
Krakowiak, D. J . Tetrahedron Lett. 1990, 31, 1077.
(26) (a) Krakowiak, K. E.; Bradshaw, J . S.; Izatt, R. M. J . Heterocycl.
Chem. 1990, 27, 1585. (b) Bradshaw, J . S.; Krakowiak, K. E.; An, H.;
Izatt, R. M. Ibid. 1990, 27, 2113.
The results obtained with some representative ep-
oxides in the presence of macrocycles 7 and 14 as catalyst

Halogenative Cleavage of Epoxides
J . Org. Chem., Vol. 63, No. 5, 1998 1457
are summarized in Table 2 and are compared with the
corresponding results obtained in the reaction of the same
epoxides in the absence of catalyst (entries 4, 5, 9, 16,
20, and 27). On the other hand, for comparison, some
other methods for conversion of epoxides to the corre-
sponding halohydrins are given in Table 2, entries 6, 10-
13, and 32. When epoxides were allowed to react in the
presence of catalyst, increases in yield and regioselectiv-
ity were observed in all of the reactions studied. The
increase appeared to be largely dependent on the type
(Table 1) and amount of catalyst. Generally, the opti-
mum amounts of the catalysts were found to be 0.1 mol
for 1 mol of epoxide and halogen. However, in the case
of styrene oxide and phenoxypropylene oxide reactions
occurred in the presence of even 0.05 mol of catalyst 7
(Table 3 and Table 2, entries 2 and 18).
ethers with elemental halogens,28,29 halogenative cleavage
of epoxides occurs according to the following four-step
mechanism:
The first step involves the formation of a 1:2 or 1:1
molecular complex between macrocycle and elemental
halogen, in which halogen ion (X3-) exists as a contact
ion pair:
macrocycle + 2X2 h (macrocycle‚‚‚X+) X3
-
or
2 macrocycle + 2X2 h (2 macrocycle‚‚‚X+) X3 (1)
-
In the second step this complex is further decomposed
-
to release X3 ion into solution as
However, other factors can exert a controlling influ-
ence, such as (1) steric hindrance of epoxides, (2) the rate
of admixing the reagents, (3) the order in which the
reagents are combined, and (4) the nature of solvent.
Each can have a pronounced effect on the observed ratio
of halohydrin isomers and overall yield.
A comparison of the reaction of epoxides with elemen-
tal bromine or iodine in the presence of a macrocyclic
catalyst indicates that an increase in steric hindrance
at the epoxide ring results in a general decrease in the
rate of halohydrin formation (for example, compare Table
2, entry 1 with entry 29).
(macrocycle‚‚‚X+) X3- f (macrocycle‚‚‚X+) X3 (2)
-
Therefore, in this way, molecular iodine or bromine is
converted to a nucleophilic halogen species in the pres-
ence of a suitable macrocycle and, in the third step, this
ion participates in the ring opening reaction of epoxides:
Finally, the catalyst is regenerated in step 4.
The order and rate in which the reagents are combined
were found to exert a subtle influence on yield and
regioselectivity in both bromohydrin and iodohydrin
formation. For example, if bromine is added to epoxide
before catalyst is added, two bromohydrin isomers are
produced, but if the epoxide is added to catalyst and then
bromine is added dropwise over a period of time, only
one isomer is formed. Furthermore, fast addition of
bromine reduced regioselectivity, too (Table 2, entry 21).
The reactions are completely anti-sterioselective as
shown for cyclohexene oxide (Table 2, entries 29 and 31),
in which only the trans isomers were detected. A contra-
Markovnikov-type27 regioselectivity is generally observed
in these reactions. Interestingly, in many cases, this type
of regioselectivity appears to be the opposite of that
observed in ring opening of the same epoxides with
hydrohalogenic acids, under classic acidic conditions14a
(Table 2, entries 12 and 13).
These steps occur continuously until all of the epoxides
and halogen are consumed, and after workup, the cata-
lyst can be recovered easily.
On the other hand, when catalyst is not present,
cleavage of epoxides can occur via two limiting mecha-
nistic pathways, either electrophilic attack by molecular
halogen, behaving as Lewis acid, giving the more stable
carbonium ion-like transition state (A), or via nucleophilic
attack by halide ion on the epoxide or epoxide-halogen
complex, giving the more stable transition state (B):
The results of ring opening of styrene oxide in the
presence of macrocycle 7 in various aprotic solvents are
summarized in Table 3. The iodination and bromination
reactions proceed most cleanly in CH2Cl2, CHCl3, CH3CN,
and benzene solution, while those done in THF and
acetone lead to a lower yield of halohydrins.
Discu ssion
Most Lewis acidic compounds, such as titanium halides,
foster electophilic opening of the epoxide ring to yield
transition state A. When weaker Lewis acids are em-
ployed, namely bromine or iodine, nucleophilic attack, by
the halide ions generated should be fostered and transi-
tion state B may be expected to be lower in energy. In
The regiochemical mode of epoxide cleavage by elemen-
tal iodine or bromine in the presence of macrocycle
catalyst can be viewed as occurring via nucleophilic
attack by halide ion on the less sterically hindered
epoxide carbon. This mechanism closely resembles the
SN2 model for aliphatic nucleophilic displacement. On
the basis of our previous study on macrocycle diamides
17-19 and other works on the complexation of crown
(28) Lowry, T. H.; Richardson , K. S. Mechanism and Theory in
Organic Chemistry, 3rd ed.; Harper & Row: New York, 1987; pp 327-
423.
(27) Dela More, P. B. D.; Bolton, R. Electrophilic Addition to
Unsaturated Systems; Elsevier Scientific: New York, 1966.
(29) Semnani, A.; Shamsipur, M. J . Chem. Soc., Dalton Trans. 1996,
2215.

1458 J . Org. Chem., Vol. 63, No. 5, 1998
Sharghi et al.
Ta ble 2. Rea ction of Ep oxid es w ith Elem en ta l Br om in e a n d Iod in e in th e P r esen ce of Rep r esen ta tive Ca ta lyst

Halogenative Cleavage of Epoxides
J . Org. Chem., Vol. 63, No. 5, 1998 1459
Ta ble 2 (Con tin u ed )
Ta ble 3. Ha logen a tion Rea ction of Styr en e Oxid e in th e
P r esen ce of 0.05 Mol of Ca ta lyst 7 in Va r iou s Solven ts a t
25 °C
namely the slow addition of epoxide to bromine or fast
addition of bromine to epoxide, before catalyst was added,
can readily be understood from the model. When the
initial epoxide was introduced (in the absence or presence
of catalyst), it would encounter an excess amount of
bromine; electrophilic attack by bromine can then occur,
giving the transition state A, and bromine anions will
attack the more substituted carbon. On the other hand,
slow addition of bromine to the mixture of catalyst and
epoxide fosters the four-step mechanism presented above
time (h)
yielda (%)
bromi-
iodi-
bromi-
iodi-
entry
solvent
CH2Cl2
CHCl3
C6H6
CH3CN
CH3COCH3
THF
nation
nation
nation
nation
1
2
3
4
5
6
0.05
0.1
0.1
0.1
0.5
0.5
0.15
0.3
0.15
0.2
2
>95
>95
>95
90
85
65
>95
90
92
90
75
-
in which all of the elemental bromine is converted to Br3
by the catalyst and it then attacks the less substituted
carbon selectively.
2
30
a
GC yield.
In conclusion, we have found that suitable macrocyclic
compounds can catalyze the regioselective ring opening
of epoxides by elemental iodine and bromine under
neutral conditions. Especially nothworthy are the ease
of catalyst regeneration and reuse, the compatibility of
these reaction conditions with a variety of sensitive
functional groups, as well as the convenience of this
procedure, which make this synthetic technique highly
useful.
this case, the cleavage leads to a mixture of secondary
alcohol and primary alcohol products.9a
The variation in yield and rate of cleaving epoxides by
elemental iodine or bromine in the presence of different
catalyst (7-16) can be satisfactory rationalized in terms
of the suggested mechanism. The macrocycles 7 and 8
are the most active catalysts in these reactions. Accord-
ing to the mechanism, in both macrocycles 7 and 8
-
complexation with I2 and, hence, elaboration of I3
occurred much faster than with other catalysts. In
support of this mechanism, reaction of catalysts with
iodine was followed by UV spectroscopy (Figure 1).
Figure 1 shows only the characteristic UV band for
macrocycles 7 and 8 (and only slightly for 13) at 364 nm,
and other macrocycle-iodine systems studied do not
show this characteristic band. This band is well known
to be specific for the formation of triiodide ion, I3-, in the
complex formation process between iodine and different
electron-pair-donating ligands.29-32 Especially in the case
of catalysts 7 and 8 this band appeared immediately and
clarified the much faster complexation of I2 with macro-
cycles 7 and 8 and consequently formation of I3-. The
most important factor, which probably contributed to the
special behavior of 7 and 8, is the presence of a C)S
group in these two macrocyclic structures.
Exp er im en ta l Section
In str u m en ta tion , An a lyses, a n d Sta r tin g Ma ter ia l.
NMR spectra were recorded using either a Bruker Avance
DPX-250 or a Varian EM 390 (90 MHz) spectrometer in pure
deuterated solvents. IR spectra were obtained on an Impact
400 D Nickolet FTIR spectrometer. Mass spectra were deter-
mined on a Shimadzu GCMS-QP 1000 EX instrument at 70
eV. UV spectra were recorded on a Philips PUB 700 spec-
trometer. The purity determination of the substrates and
reaction monitoring were accomplished by TLC on silica gel
polygram SILG/UV 254 plates or GLC on a Shimadzu GC-
10A instrument with a flame ionization detector using a
column of 15% carbowax 20 M chromosorb W acid-washed 60-
80 mesh. Elemental analyses were performed at the National
Oil Co. of Iran at Tehran Research Center. Column chroma-
tography was carried out on short columns of silica gel 60
(230-400 mesh) in glass columns (2-3 cm diameter) using
15-30 g of silica gel per 1 g of crude mixture. Melting points
were determined in open capillary tubes in a Buchi-510
circulating oil melting point apparatus. Epoxides, crown
ethers, and other chemical materials were purchased from
Fluka, Aldrich, and Merck in high purity and were used
without further purification. Compounds 1, 3, and 5 are
known compounds, and their spectroscopic and physical data
were compared with the literature data.18
The decrease in regioselectivity that results by merely
reversing the order of mixing of epoxide and halogen,
(30) Andrews, L. J .; Keefer, R. M. J . Org. Chem. 1987, 52, 2690.
(31) (a) Nour, E. M.; Shahada, L. A. Spectrochim. Acta. Part A 1988,
44, 1277. (b) Nour, E. M. Ibid. 1991, 47, 743.
(32) (a) Mizuno, M.; Tanaka, J .; Harada, I. J . Phys. Chem. 1981,
85, 1789. (b) Andrews, L.; Prochaska, E. S.; Loewenschuss, A. Inorg.
Chem. 1980, 19, 463.

1460 J . Org. Chem., Vol. 63, No. 5, 1998
Sharghi et al.
F igu r e 1. Absorption spectra of used macrocycle-iodine complexes. Spectra from bottom to top refer to macrocycles 12, 16, 10,
9, 15, 14, 13, 8, and 7:iodine complexes.
1,10-Bis(2′-m et h yl b en zoa t e)-1,4,7,10-t et r a oxa d eca n e
(2). A mixture of triethylene glycol dibromide (27.6 g, 0.1 mol)
and methyl salicylate (30.5 g, 0.2 mol) in acetone (500 mL)
containing potassium carbonate (20 g) was refluxed for 7 days.
The mixture was cooled, and the solid was filtered and solvent
evaporated. Chloroform (400 mL) was added, and the organic
layer was washed with cold 10% aqueous sodium hydroxide
solution (2 × 100 mL) and then with water (2 × 100 mL) and
was dried with anhydrous magnesium sulfate. The solvent
was evaporated to give a yellow viscous oil of 2: yield 38.5 g
(92%); Rf 0.72 (CH2Cl2-CH3OH/96-4); IR (neat) 785 (m), 1115
(s), 1225 (s), 1350 (s), 1602 (m), 1723 (m), 2978 (s), 3065 (w)
121 (base peak), 92 (41.1). Anal. Calcd for C20H20O6Cl2: C,
56.21; H, 4.68. Found: C, 56.24; H, 4.66.
Gen er a l P r oced u r e for th e Syn th esis of Ca ta lysts. A
solution of diamine (2 mmol) in CH2Cl2 (or a mixture of DMF/
CH2Cl2) (50 mL) was added quickly to a vigorously stirring
solution of diacid chloride (2 mmol) in CH2Cl2 (50 mL) at room
temperature. The mixture was stirred for a further 20 min
and then was washed with bicarbonate solution (2 × 50 mL).
The organic layer was dried over magnesium sulfate, and the
solvent was evaporated to give a solid (or oily) product. The
crude product was purified by column chromatography using
petroleum ether (bp ) 60-80 °C)-ethyl acetate as eluent.
Macrocycles 9, 11, and 12 were prepared according to ref 18,
and their spectroscopic and physical data were compared with
those in the literature data.
cm-1
;
1H NMR (CDCl3, 90 MHz) δ 3.8 (s, 6H), 3.85 (s, 4H),
3.95 (t, 4H, J ) 4.5 Hz) 4.15 (t, 4H, J ) 4.5 Hz), 6.8-7.1 (m,
4H), 7.35 (dt, 2H, J 1 ) 7.5 Hz, J 2 ) 2.0 Hz), 7.7 (dd, 2H, J 1
)
8.0 Hz, J 2 ) 2.0 Hz); MS m/z 419 (M+ + 1, 0.4), 418 (M+, 3.2),
372 (1.2), 240 (1.9), 210 (8.0), 179 (71.0), 166 (11.3), 165 (26.6),
152 (36.5), 135 (17.0), 121 (base peak), 92 (13.6), 77 (34.2).
Anal. Calcd for C22H26O8: C, 63.13; H, 6.22. Found: C, 63.14;
H, 6.20.
1,15-Dia za -3,4;12,13-d iben zo-16-(th ioca r bon yl)-5,8,11-
tr ioxa cycloh exa d eca n e-2,15-d ion e (7): yellow crystals;
75% yield; mp 160-162 °C; Rf 0.75 (CH2Cl2-CH3OH/95-5);
IR (KBr) 750 (m), 1246 (s), 1298 (s), 1508 (m), 1602 (m), 1669
1
(m), 1729 (m), 2925 (m), 3288 (s) cm-1; H NMR (CDCl3, 250
1,10-Bis(2′-ben zoic a cid )-1,4,7,10-tetr a oxa d eca n e (4). A
solution of 1,10-bis(2′-methyl benzoate)-1,4,7-tetraoxadecane
(2, 41.8 g 0.1 mol) in 10% aqueous NaOH (500 mL) was
refluxed for 24 h. The mixture was cooled, washed with
chloroform (2 × 100 mL), acidified with 6 N HCl, and extracted
with CH2Cl2 (5 × 150 mL). The solvent was evaporated and
the resulting yellow solid was recrystallized from acetone to
give white crystals of 3: yield 39 g (100%); mp 111-113 °C;
Rf 0.55 (CH2Cl2-CH3OH/96-4); IR (KBr) 780 (m), 1100 (m),
1230 (s), 1350 (s), 1602 (m), 1716 (s), 2864 (s), 2980 (s), 3073
(w), 3280 (br s) cm-1; 1H NMR (CDCl3, 90 MHz) δ 3.8 (s, 4H),
3.85 (t, 4H, J ) 4.5 Hz), 4.25 (t, 4H, J ) 4.5 Hz), 6.8-7.1 (m,
4H), 7.35 (dt, 2H, J 1 ) 8.0, J 2 ) 2.0 Hz), 7.9 (dd, 2H, J 1 ) 8.0
Hz, J 2 ) 2.0 Hz), 8.5 (b, 2H); MS m/z 373 (M+ - OH, 10.0),
210 (2.6), 209 (17.5), 166 (4.0), 165 (34.9), 152 (4.9), 138 (15.6),
121 (base peak), 92 (10.9). Anal. Calcd for C20H22O8: C, 61.54;
H, 5.64. Found: C, 61.53; H, 5.67.
MHz) δ 3.66 (t, 4H, J ) 4.00 Hz), 4.23 (t, 4H, J ) 4.00 Hz),
6.90 (dd, 2H, J 1 ) 8.25 Hz, J 2 ) 0.5 Hz), 7.07 (dt, 2H, J 1
)
7.25 Hz, J 2 ) 1.00 Hz), 7.43 (dt, 2H, J 1 ) 7.75 Hz, J 2 ) 1.75
Hz), 7.76 (dd, 2H, J 1 ) 7.75 Hz, J 2 ) 1.75 Hz), 12.37 (b, 2H);
MS m/z 387 (M+ + 1, 0.5), 386 (M+, 2.3), 267 (4.7), 253 (0.3),
213 (5.5), 196 (17.2), 179 (10.9), 165 (19.5), 121 (base peak),
120 (87.1), 105 (12.6), 92 (65.5); UV (CHCl3) λ 260.8 (ꢀmax
)
26 780) , 310 nm (ꢀ ) 19 200). Anal. Calcd for C19H18N2O5S:
C, 59.07; H, 4.66; N, 7.25. Found: C, 59.11; H, 4.69; N, 7.23.
1,18-Diaza-3,4;15,16-diben zo-19-(th iocar bon yl)-5,8,11,14-
tetr a oxa cyclon on a d eca n e-2,18-d ion e (8): yellow crystals;
70% yield; mp 150-152 °C; Rf ) 0.7 (CH2Cl2-CH3OH/95-5);
IR (KBr) 752 (m), 1245 (s), 1300 (s), 1517 (m), 1600 (m), 1669
1
(w), 1730 (m) 2925 (m), 3325 (s) cm-1; H NMR (CDCl3, 250
MHz) δ 3.52 (s, 4H), 3.76 (t, 4H, J ) 5.00 Hz), 4.33 (t, 4H, J
) 5.00 Hz), 6.97 (dd, 2H, J 1 ) 8.25 Hz, J 2 ) 0.50 Hz), 7.06 (dt,
2H, J 1 ) 7.25 Hz, J 2 ) 1.00 Hz), 7.48 (dt, 2H, J 1 ) 7.75 Hz, J 2
) 1.75 Hz), 7.79 (dd, 2H, J 1 ) 8.00 Hz, J 2 ) 1.75 Hz), 12.35
(d, 2H); MS m/z 431 (M+ + 1, 0.5), 430 (M+, 1.5), 223 (1.3),
196 (17.1), 165 (20.5), 147 (10.6), 121 (base peak), 120 (50.3),
62 (45.3), 43(41); UV (CHCl3) λ 260.2 (ꢀmax ) 25 800), 308 nm
(ꢀ ) 18 500). Anal. Calcd for C21H22N2O6S: C, 58.60; H, 5.12;
N, 6.51. Found: C, 58.63; H, 5.09; N, 6.47.
1,10-Bis(2′-ben zoyl ch lor id e)-1,4,7,10-tetr a oxa d eca n e
(6). 1,10-Bis(2′-benzoic acid)-1,4,7-tetraoxadecane (4, 9.75 g,
0.025 mol) was heated in thionyl chloride (50 mL) for 4 h at
50-60 °C. The thionyl chloride was evaporated at low
temperature to give 6 as a yellow solid in 95% yield: mp 47-
49 °C; IR (KBr) 775 (m), 1153 (s), 1255 (s), 1598 (m), 1780(s),
1
2890 (s), 3055 (w) cm-1; H NMR (CDCl3, 90 MHz) δ 3.8 (s,
1,18,21-Tr ia za -3,4;15,16-d iben zo-5,8,11,14-t et r a oxa cy-
clotetr a eicosa n e-2,17-d ion e (10): white solid; 80% yield;
mp 59-61 °C; Rf ) 0.14 (CH2Cl2-CH3OH/96-4); IR (KBr) 760
(s), 1105 (s), 1228 (s), 1300 (s), 1600 (m), 1650 (s), 2925 (m),
4H), 3.85 (t, 4H, J ) 4.5 Hz), 4.25 (t, 4H, J ) 4.5 Hz), 6.8-7.1
(m, 4H), 7.35 (dt, 2H, J 1 ) 8.0 Hz, J 2 ) 2.0 Hz), 8.0 (dd, 2H,
J 1 ) 8.0 Hz, J 2 ) 2.0 Hz); MS m/z 328 (M+ - COCl2, 10.1),
210 (4.5), 209 (10.9), 166 (4.1), 165 (36.2), 152 (4.2), 138 (19.9),
1
3380 (br s) cm-1; H NMR (CDCl3, 250 MHz) δ 1.45 (t, 1H, J

Halogenative Cleavage of Epoxides
J . Org. Chem., Vol. 63, No. 5, 1998 1461
) 4.25 Hz), 3.00 (dt, 4H, J 1 ) 4.50 Hz, J 2 ) 2.00 Hz), 3.7 (t,
4H, J ) 4.50 Hz), 3.80 (s, 4H), 3.90 (dt, 4H, J 1 ) 4.50 Hz, J 2
) 2.00 Hz), 4.10 (t, 4H, J ) 4.50 Hz), 6.80 (dd, 2H, J 1 ) 8.00
Hz, J 2 ) 1.75 Hz), 7.00 (dt, 2H, J 1 ) 7.00 Hz, J 2 ) 0.75 Hz),
2-Br om ocycloh exa n ol: 1H NMR (CDCl3, 250 MHz) δ
1.26-1.42 (m, 3H), 1.78-1.98 (m, 3H), 2.18-2.32 (m, 1H),
2.32-2.38 (m, 1H), 2.68 (s, 1H), 3.58-3.64 (m, 1H), 3.82-3.92
(m, 1H); 13C NMR (CDCl3, 250 MHz) δ 19.79, 24.48, 27.02,
33.95, 36.59, 62.13, 75.66; IR (neat) 690 (s), 793 (w), 865 (m),
960 (s), 1038 (m), 1075 (br s), 1123 (m), 1189 (s), 1372 (m),
7.20 (dt, 2H, J 1 ) 8.00 Hz, J 2 ) 2.00 Hz), 8.00 (dd, 2H, J 1
)
8.00 Hz, J 2 ) 2.00 Hz), 8.50 (b, 2H); MS m/z 457 (M+, 0.5),
428 (8.6), 415 (3.8), 372 (11.7), 209 (16.3), 165 (42.1), 121 (base
peak), 105 (5.4), 73 (13.8), 64 (10.4); UV (CHCl3) λ 228.8 (ꢀmax
) 21 500), 283.2 nm (ꢀ ) 7500). Anal. Calcd for C24H31N3O6:
C, 63.02; H, 6.78; N, 9.19. Found: C,63.04; H, 6.75; N, 9.21.
1,15-Dia za -2,3,4-n a p h th yl-8,11,14-tr ioxa cycloh exa d ec-
a n e-6,16-d ion e (13): white crystals; 69% yield; mp 47-48
°C; Rf ) 0.35 (CH2Cl2-CH3OH/96-4); IR (KBr) 757 (s), 810
(s), 987 (w), 1140 (s), 1205 (m), 1272 (m), 1327 (m), 1425 (m),
1460 (s), 2882 (s), 2960 (br s), 3425 (br s) cm-1
.
2-Iod ocycloh exa n ol: 1H NMR (CDCl3, 250 MHz) δ 1.26-
1.44 (m, 3H), 1.75-1.95 (m, 3H), 2.15-2.3 (m, 1H), 2.3-2.35
(m, 1H), 2.72 (s, 1H), 3.58-3.62 (m, 1H), 3.9-4.0 (m, 1H); 13
C
NMR (CDCl3, 250 MHz) δ 19.79, 24.51, 26.56, 32.75, 35.40,
59.84, 71.59; IR (neat) 690 (s), 790 (w), 870 (m), 948 (s), 1038
(w), 1082 (br s), 1123 (m), 1189 (s), 1372 (m), 1462 (s), 2882
(s), 2960 (br s), 3425 (br s) cm-1
.
1590 (w), 1653 (s), 2840 (m), 2925 (m), 3045 (w), 3235 (s) cm-1
;
1-P h en oxy-3-br om o-2-p r op a n ol: 1H NMR (CDCl3, 250
MHz) δ 2.75 (s, 1H), 3.61 (d, 2H, J ) 5.0 Hz), 4.03 (q, 1H, J )
2.0 Hz), 4.11 (d, 2H, J ) 7.0 Hz), 6.78 (d, 1H, J ) 5.0 Hz),
6.94 (d, 2H, J ) 8.0 Hz), 7.35 (m, 2H); 13C NMR (CDCl3, 250
MHz) δ 69.58, 69.77, 69.93, 115.01, 116.82, 121.86, 129.99,
132.79; IR (neat) 641 (w), 688 (m), 756 (m), 823 (m), 1038 (s),
1112 (w), 1239 (s), 1375 (m), 1494 (s), 1588 (s), 2878 (m), 2925
1H NMR (CDCl3, 250 MHz) δ 3.83 (s, 8H), 4.33 (s, 4H), 7.51
(dt, 2H, J 1 ) 8.25 Hz, J 2 ) 2.25 Hz), 7.78 (d, 2H, J ) 7.25 Hz),
7.88 (d, 2H, J ) 7.00 Hz), 9.25 (s, 2H); MS m/z 346 (M+ + 2,
0.3), 345 (M+ + 1, 2.1), 344 (M+, 10.1), 225 (4.5), 197 (6.9),
185 (10), 184 (25.5), 182 (4.5), 169 (11.4), 155 (3.8), 97 10.1),
83 (13.6), 69 (26), 43 (base peak), 41 (52.4); UV (CHCl3) λ 246.2
(ꢀmax ) 1040), 307.8 nm (ꢀ ) 760). Anal. Calcd for C18H20N2-
O5: C, 62.79; H, 5.81; N, 8.14. Found: C, 62.83; H, 5.79; N,
8.16.
(s), 3059 (m), 3415 (br s) cm-1
.
1-P h en oxy-3-iod o-2-p r op a n ol: 1H NMR (CDCl3, 250
MHz) δ 3.1 (s, 1H), 3.48 (d, 2H, J ) 5.0 Hz), 4.06 (q, 1H, J )
2.0 Hz), 4.13 (d, 2H, J ) 7.0 Hz), 6.78-6.9 (m, 3H), 7.36 (m,
2H); 13C NMR (CDCl3, 250 MHz) δ 67.18, 69.67, 70.01, 114.98,
116.87, 121.79, 129.89, 132.86; IR (neat) 650 (w), 678 (w), 760
(m), 823 (m), 1038 (s), 1113 (w), 1240 (s), 1375 (m), 1494 (s),
Gen er a l P r oced u r e for Ha logen a tive Clea va ge of Ep -
oxid es. Epoxide (1 mmol) in CH2Cl2 (5 mL) was added to a
stirred solution of catalyst (0.1 mmol) in CH2Cl2 (5 mL) at room
temperature. Next, a solution of elemental halogen (1 mmol)
in CH2Cl2 (5 mL) was added dropwise during 15 min to the
above mixture. The progress of reaction was monitored by
TLC and GLC. After complete disappearance of the starting
material, the reaction mixture was washed with 10% aqueous
Na2S2O3 (2 × 10 mL) and water (2 × 10 mL). The aqueous
layer was further extracted with CH2Cl2 (2 × 10 mL). The
combined organic layer was dried over anhydrous MgSO4 and
evaporated to give crude alcohol-catalyst. The crude products
were purified by crystallization in diethyl ether. After cooling,
the catalyst was filtered off and washed with cold ether. The
filtrate was evaporated and pure halohydrin obtained. The
halohydrins obtained throughout this procedure were identi-
fied by comparision, where possible, with authentic samples
prepared in accordance with literature procedures.9b,14a,13,33
1-Br om o-2-octa n ol: 1H NMR (CDCl3, 250 MHz) δ 0.89 (t,
3H, J ) 6.5 Hz), 1.25-1.63 (m, 8H), 1.86 (q, 2H, J ) 7.1 Hz),
2.22 (s, 1H), 3.42 (t, 2H, J ) 7.1 Hz), 3.75-3.84 (m, 1H); 13C
NMR (CDCl3, 250 MHz) δ 14.01, 22.52, 29.14, 31.68, 35.05,
40.73, 71.02; IR (neat) 720 (m), 830 (m), 1050 (s), 1075 (s),
1125 (m), 1225 (m), 1265 (m), 1385 (m), 1425 (m), 1470 (s),
1588 (s), 2877 (m), 2927 (s), 3050 (m), 3418 (br s) cm-1
.
1-(Isop r op yloxy)-3-br om o-2-p r op a n ol: 1H NMR (CDCl3,
250 MHz) gd 1.16 (d, 6H, J ) 4.0 Hz), 2.78 (s, 1H), 3.42-3.65
(m, 5H), 3.92 (m, 1H); 13C NMR (CDCl3, 250 MHz) δ 22.34,
35.40, 69.59, 70.40, 72.70; IR (neat) 675 (m), 798 (w), 923 (m),
1051 (s), 1085 (s), 1125 (s), 1375 (m), 1467 (m), 2871 (m), 2925
(m), 2972 (s), 3435 (br s) cm-1
.
1-(Isop r op yloxy)-3-iod o-2-p r op a n ol: 1H NMR (CDCl3,
250 MHz) δ 1.15 (d, 6H, J ) 4 Hz), 2.92 (s, 1H), 3.38-3.59 (m,
5H), 3.79 (m, 1H); 13C NMR (CDCl3, 250 MHz) δ 22.78, 36.2,
67.3, 69.8, 72.5; IR (neat) 743 (w), 923 (m), 1050 (s), 1085 (s),
1128 (s), 1375 (m), 1467 (m), 2870 (m), 2926 (m), 2975 (s), 3472
(br s) cm-1
.
2-Br om o-1-p h en yleth a n ol: 1H NMR (CDCl3, 250 MHz)
δ 1.98 (s, 1H), 4.01 (m, 2H), 4.98 (t, 1H, J ) 5.0 Hz), 7.19-
7.39 (m, 5H); 13C NMR (CDCl3, 250 MHz) δ 57.39, 67.97,
128.32, 129.30, 129.37, 138.98; IR (neat) 689 (m), 766 (m), 823
(m), 1036 (s), 1115 (w), 1233 (s), 1375 (m), 1494 (m), 1600 (s),
2875 (m), 2935 (s), 3064 (m), 3405 (br s) cm-1
.
2-Iod o-1-p h en yleth a n ol: 1H NMR (CDCl3, 250 MHz) δ
2.02 (s, 1H), 3.76 (d, 2H), 4.78 (t, 1H, J ) 5.0 Hz), 7.17-7.35
(m, 5H); 13C NMR (CDCl3, 250 MHz) δ 54.69, 66.90, 128.22,
129.10, 129.21, 138.17; IR (neat) 748 (m), 915 (m), 1032 (s),
1121 (w), 1243 (s), 1365 (m), 1492 (m), 1602 (s), 2885 (m), 2930
2860 (vs), 2935 (vs), 2970 (vs), 3380 (br s) cm-1
.
1-Iod o-2-octa n ol: 1H NMR (CDCl3, 250 MHz) δ 0.89 (t,
3H, J ) 7.0 Hz), 1.26-1.58 (m, 10H), 2.24 (s, 1H), 3.24-3.55
(m, 3H); 13C NMR (CDCl3, 250 MHz) δ 14.09, 16.45, 22.62,
25.56, 29.12, 31.70, 36.89, 70.91; IR (neat) 725 (m), 1015 (br
s), 1105 (m), 1130 (m), 1185 (s), 1385 (s), 1425 (s), 1465 (s),
(s), 3061 (m), 3398 (br s) cm-1
.
1475 (s), 2870 (vs), 2940 (vs), 2970 (s), 3400 (br s) cm-1
.
Ack n ow led gm en t. We are thankful to Shiraz Uni-
versity Research Council for their financial support.
(33) Masuda, H.; Takasa, K.; Nishio, M.; Hasegawa, A.; Nishiyama,
Y.; Ishii, Y. J . Org. Chem. 1994, 59, 5550.
J O971453Y