Conversion of epoxides into 2-hydroxyethyl thiocyanates with NH 4SCN in the presense of 2,6-BIS[2-(O-amino phenoxy)methyl]-4-bromo-1- methoxybenzene (BABMB) as catalyst

Article abstract of DOI:10.1080/10426500490262685

A convenient and efficient procedure for the ring-opening of 1,2-epoxyethanes with ammonium thiocyanate in the presence of 2,6-bis[2-(o-aminophenoxy)methyl]-4-bromo-1-methoxybenzene (BABMB) is described. In this study, a reagent and conditions have been discovered with which the individual 2-hydroxyethyl thiocyanates can be synthesized in high yield and with more than 90% regioselectivity. Thus, several 2-hydroxyethyl thiocyanates, useful intermediates toward biological-active molecules, are easily obtained in very good yields.

Full text of DOI:10.1080/10426500490262685

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CONVERSION OF EPOXIDES INTO 2-HYDROXYETHYL
THIOCYANATES WITH NH4SCN IN THE PRESENSE OF
2,6-BIS[2-(O -AMINO PHENOXY)METHYL]-4-BROMO-1-
METHOXYBENZENE (BABMB) AS CATALYST
Khodabakhsh Niknam a
a Persian Gulf University, Bushehr, Iran
Published online: 12 Aug 2010.
To cite this article: Khodabakhsh Niknam (2004) CONVERSION OF EPOXIDES INTO 2-HYDROXYETHYL THIOCYANATES WITH
NH4SCN IN THE PRESENSE OF 2,6-BIS[2-(O -AMINO PHENOXY)METHYL]-4-BROMO-1-METHOXYBENZENE (BABMB) AS CATALYST,
Phosphorus, Sulfur, and Silicon and the Related Elements, 179:3, 499-506, DOI: 10.1080/10426500490262685
To link to this article: http://dx.doi.org/10.1080/10426500490262685
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Phosphorus, Sulfur, and Silicon, 179:499–506, 2004
ꢀC
Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490262685
CONVERSION OF EPOXIDES INTO
2-HYDROXYETHYL THIOCYANATES WITH NH4SCN
IN THE PRESENSE OF 2,6-BIS[2-(O-AMINO
PHENOXY)METHYL]-4-BROMO-1-METHOXYBENZENE
(BABMB) AS CATALYST
Khodabakhsh Niknam
Persian Gulf University, Bushehr, Iran
(Received August 5, 2003; in final form September 9, 2003)
A convenient and efficient procedure for the ring-opening of 1,2-
epoxyethanes with ammonium thiocyanate in the presence of 2,6-bis[2-
(o-aminophenoxy)methyl]-4-bromo-1-methoxybenzene (BABMB) is de-
scribed. In this study, a reagent and conditions have been discovered
with which the individual 2-hydroxyethyl thiocyanates can be syn-
thesized in high yield and with more than 90% regioselectivity.
Thus, several 2-hydroxyethyl thiocyanates, useful intermediates toward
biological-active molecules, are easily obtained in very good yields.
Keywords: Ammonium thiocyanate; catalyst; epoxide; podand diamine;
thiocyanohydrin
Thiocanates are important intermediates in agricultural and pharma-
ceutical chemistry. 2-Hydroxyethyl thiocyanates represent an interest-
ing subclass having multiple modes of reactivity. Synthetic access by
oxirane ring opening with thiocyanate has been limited by a further
reaction to give thiiranes.1,2 The formation of thiiranes from the reac-
tion of epoxides and thiocyanate ion has been proposed to occur through
the intermediacy of the corresponding β-hydroxy thiocyanate, but this
intermediate has not been isolated due to its rapid conversion to the
corresponding thiirane.2−4 There are two methods reported in the liter-
ature for the synthesis of 2-hydroxyethyl thiocyanates. In one method,
2-hydroxyethyl thiocyanates are prepared by the opening of a cyclic
I gratefully acknowledge the support of this work by the Persian Gulf University
Research Council. Also, I thank Miss N. Moghtamed Rad for running the UV spectra.
Address correspondence to Khodabakhsh Niknam, Department of Chemistry, Faculty
of Science, Persian Gulf University, Bushehr 75168, Iran. E-mail: kh niknam@yahoo.com
or niknam@pgu.ac.ir
499

500
K. Niknam
2-Hydroxyethyl
R 1 (a–h)
thiocyanate 2 (a–h)
Ph
PhOCH2
Cyclohexene oxide
CH3(CH2)3
Indene oxide
i-PrOCH2
a
b
c
d
e
f
A
B
C
D
E
F
G
h
CH2 CHCH2OCH2
ClCH2
g
h
sulfate with NH4SCN to form the corresponding β-sulfate, which is
hydrolyzed to the 2-hydroxyethyl thiocyanates. A second method em-
ploys an addition to the 1,2-epoxyethanes of thiocyanic acid generated
in situ at low temperature.5 For these syntheses, it has been reported
that the presence of some hydroquinone or DDQ is required to stabilize
the produced 2-hydroxyethyl thiocyanates, and to inhibit its conver-
sion to thiirane.3,6 Although reagents, such as [Ti(O-iPr)4/NH4SCN],7
Ph3P(SCN)2,8 [TiCl3(or ZnCl2)/KSCN],9 [Pd(PPh3)4/NH4SCN],10 and
TMSNCS (Cat. TBAF),11 are useful, they are limited to specific oxi-
ranes, and are not applicable as versatile reagents in the preparation
of 2-hydroxyethyl thiocyanates.11
The properties of cyclic crown ethers are approximated by acyclic
neutral ligands (podands). Variation of the endo-polarophilicity/exo-
lipophilicity balance, complex stability, ion selectivity can often be ac-
complished more easily, with greater versatility, and at less expense
with acyclic polyether than with their cyclic counterparts: Complex-
ation and decomplexation are generally faster in acyclic system and
the pseudocavity usually has greater conformational flexibility.12 In
conjunction with the ongoing work in our laboratory on the synthe-
sis and formation of complex heterocyclic compounds containing donor
nitrogen atoms, with different molecules,13,14 we found that podand di-
amine {2,6-bis[2-(o-aminophenoxy) methyl]-4-bromo-1-methoxybenz-
ene} (BABMB) efficiently catalyzed the addition of ammonium thio-
cyanate to epoxide to form 2-hydroxyethyl thiocyanate. Recently, we
prepared13e,14 BABMB and used it as a new catalyst for the conversion
of epoxide into halohydrins with elemental iodine and bromine. In this
study, I wish to report the results of the reactions of some epoxides with

2-Hydroxyethyl Thiocyanates
501
ammonium thiocyanate in the presence of a substoichiometric amount
of podand diamine BABMB (1).
RESULTS AND DISCUSSION
Aromatic amines are used widely as intermediates for dyes, photo-
graphic materials, pharmaceutical and agricultural chemicals and as
antioxidants. Also, diamines are used as starting materials for the syn-
thesis of polymers, azacrowns, and macrocyclic diamides.
Epoxides of convenient volatility to allow GC analysis were chosen for
the study. The results of the reactions of styrene oxide with thiocyanate
ion in the presence of BABMB are summarized in Table I. In each case,
cleavage of epoxide ring occurs and upon thiosulfate workup, the cor-
responding thiocyanohydrin was obtained. In comparison, the cleavage
behavior of styrene oxide with ammonium thiocyanate in the absence
of the catalyst is given in entry 3 of Table I.
As shown in Table I, yields of thiocyanation with this new method-
ology were quite good, and the reaction times were very short. How-
ever, the reaction of the styrene oxide with an excess of ammonium
thiocyanate in the absence of the catalyst afforded the correspond-
ing thiirane in 35% yield when the reaction mixture was refluxed for
3.5 h. An alternative preparation of 2-hydroxyethyl thiocyanate by
TABLE I Reaction of Styrene Oxide with NH4SCN in the Presence of the
Representative Catalyst
Reaction
conditions
Reaction
Entry
1
Catalyst
BABMB
Product(s)
time (min) Yield%a
NH4SCN/CH3CN 70◦C
10
91 (4:1)
2
3
4
5
BABMB
KSCN/CH3CN 70◦C
120
210
120
240
10
35
35
30
—
NH4SCN/CH3CN 70◦C
Pd(PPh3)4 NH4SCN/N2 THF/Reflux
Ti(o-iPr)4
NH4SCN/THF Reflux
6
7
ZnCl2
DDQ
KSCN/THF Reflux
180
50
60
NH4SCN/CH3CN Reflux
91(1:8)
aDetermined by GC.

502
K. Niknam
TABLE II Thiocyanative Cleavage of Styrene Oxide
with NH4SCN in the Presence of BABMB as Catalyst
in Different Solvents under Reflux Condition
Entry
Solvent
Time (min)
Yielda(%)
1
2
3
4
5
6
7
8
CH3CN
CH3CN
C6H6
t-BuOH
EtOH
THF
CH2Cl2
1,4-dioxane
10
200b
120
60
60
60
91
c
<20
54
39
35
<20
40
60
60
aDetermined by GC.
bIn the presence of excess of NH4SCN.
c35% of the corresponding thiirane was obtained.
the reaction of styrene oxide with KSCN was examined. This route,
however, is not a good one for the synthesis of 2-hydroxyethyl thio-
cyanates and gave a 10% yield of the corresponding thiirane (Table I,
entry 2).
The results of the ring opening of styrene oxide in the presence of
BABMB using various solvents are summarized in Table II. Thiocya-
nation reactions proceed very cleanly employing CH3CN, while those
performed in C6H6, t-BuOH, THF, EtOH, 1,4-dioxane and CH2Cl2 led
to a lower yield of the thiocyanohydrins.
To ascertain the scope and limitation of the present reaction, several
oxiranes were examined; these results are summarized in Table III.
By comparison, a number of methods7−10 for the conversion of oxiranes
to the corresponding 2-hydroxyethyl thiocynates are given in entries
4–7 (Table I), and entry 7 (Table III). When epoxides were allowed to
react in the presence of BABMB, the yield and regioselectivity, were
higher than that observed in all of the reactions conditions studied.
Generally, the optimum amount of catalyst was found to be 0.1 mmol
for 1 mmol of epoxide and NH4SCN. However, other factors can ex-
ert a controlling influence, such as (1) steric hindrance of epoxides,
(2) the nature of solvent, and (3) electron-donating or withdrawing
groups bonded to the epoxide. Each one can have a pronounced effect
on the observed ratio of 2-hydroxyethyl thiocyanate isomers and the
overall yield.
As shown in Table III (entry 6), in which only the trans isomer is
given, the reactions are completely anti stereoselective. As for the re-
gioselectivity, an attack of the nucleophile preferentially occurs at the

2-Hydroxyethyl Thiocyanates
503
TABLE III Reaction of Epoxides with NH4SCN in the Presence of BABMB
Catalyst
Reaction
conditions
Reaction
Entry Epoxide
1
Product(s)
time (min) Yield%a
NH4SCN/CH3CN 70◦C
NH4SCN/CH3CN 70◦C
NH4SCN/CH3CN 70◦C
NH4SCN/CH3CN 70◦C
NH4SCN/CH3CN 70◦C
NH4SCN/CH3CN 70◦C
45
110
70
90
90 (4:1)
83
2
3
4
5
75
78
65
79
6
7
8
40
—
92
H2Qb(cat.) KSCN/H3PO4
H2O/Et2O
485a
81
NH4SCN/CH3CN 70◦C
90
aDetermined by GC.
bHydroquinone has been used to stablize 2-hydroxycyclohexyl thiocyanate (see Van
Tamelen5a).
less-substituted oxirane carbon. An anti-Markovnikov-type15 regiose-
lectivity is generally observed in these reactions, except for the reactions
of styrene oxide (Table I, entry 1), and indene oxide (Table III, entry 2),
which produced 17% and 20% of their regioisomer, respectively, and
only one isomer was obtained. In these reactions 5–10% of the corre-
sponding thiiranes were also formed, which could easily be isolated by
column chromatography.
The regiochemical mode of epoxide cleavage by ammonium thio-
cyanate in the presence of BABMB can be viewed as occurring via nucle-
ophilic attack by thiocyanate 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 macro-
cyclic diamides and other works on the complexation of crown ethers,
azophenol-dyed crown ethers and podand diamines with elemental
halogens, alkaline metal ions, ammonium cation, and alkylamine,13−18
conversion of epoxide to 2-hydroxy thiocyanate occurs according to the
following four-step mechanism: The first step involves the formation of
a 1:1 molecular complex between BABMB and NH4SCN in which the

504
K. Niknam
thiocyanate ion (SCN−) exists as a contact ion pair:
+
−
ꢀ
ꢁ
diamine + NH SCN
[diamine. . . . NH ]SCN
(1)
4
4
In the second step, this complex is further decomposed to release
SCN− ion into the solution as:
(diamine. . . . NH4+)SCN− → [diamine. . . . NH+4 ] + SCN−
(2)
Therefore, in this way, SCN− ion is produced as a nucleophilic species
in the presence of BABMB, and in the third step, this ion participates
in the ring-opening reaction of epoxides:
(3)
Finally, the catalyst is regenerated in step 4:
(4)
These steps occur continuously until all of the epoxides and ammo-
nium thiocyanate are consumed. The variation in yield and rate of epox-
ide ring opening by SCN− in the presence of BABMB can be rationalized
in terms of the suggested mechanism.
In support of this mechanism, interaction of BABMB with NH4SCN
was followed by UV spectroscopy (Figure 1). This figure shows the elec-
tronic absorption spectra of NH4SCN, BABMB catalyst, and BABMB
catalyst in the presence of NH4SCN in CH3CN solution. As we can see,
addition of NH4SCN to BABMB catalyst results in the appearance of a
new absorption maximum at 290 nm. As is obvious, BABMB/NH4SCN
interaction will result in a strong absorption shift of about 20 nm toward
longer wavelengths.
In conclusion, this new method appears to be highly competitive with
the other methods reported in the literature. The reaction occurs in
neutral and mild conditions on the acid-sensitive substrates and thio-
cyanohydrins were obtained in high yields and regioselectivity. In ad-
dition, in comparison with our previous methods,13e BABMB is less ex-
pensive, has fewer steps needed for the preparation, and has a higher
overall yield.

2-Hydroxyethyl Thiocyanates
505
FIGURE 1 Absorption spectra from bottom to top refer to NH4SCN (1),
BABMB (2), and BABMB in the presence of NH4SCN (3), in CH3CN solution.
EXPERIMENTAL
General
Some 1,2-epoxyethanes and other chemical materials were purchased
from Fluka and Merck in high purity. Products were characterized
by comparison of their physical data with those of authentic samples.
The nmr spectra were recorded on a Bruker Avance DPX instrument
(250 MHz). IR spectra were recorded on a Shimadzo 450 spectropho-
tometer. Melting points were determined in open capillaries with a
Galen-Kamp melting point apparatus. TLC accomplished the purity
determination of the substrates and reaction monitoring on silica gel
polygram SILG/UV 254 plates.
General Procedure for the Conversion
of 1,2-Epoxyethanes to 2-Hydroxyethyl Thiocyanate
Using BABMB as a Catalyst
To a mixture of epoxide (10 mmol) and NH4SCN (10 mmol, 0.76 g)
in acetonitrile (30 mL) was added a solution of the catalyst (1 mmol) in
CH2Cl2 (5 mL), and the mixture was stirred and heated in an oil bath
at 70◦C for 10–90 min. The reaction was monitored by TLC or GC. Af-
ter completion of the reaction, the mixture was filtered and the solvent
was evaporated. Chromatography of the crude product was performed
on a column of silica gel eluted first with n-hexane for the separation

506
K. Niknam
of thiirane, followed by using C6H14/CH2Cl2 (1:1) for the separation of
2-hydroxyethyl thiocyanate as a pale yellow liquid. The 2-hydroxyethyl
thiocyanates obtained throughout this procedure were identified by
comparison, where possible, with authentic samples prepared in ac-
cordance with literature procedures.3,8,11,13e
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