Combination of NH2OH·HCl and NaIO4: an effective reagent for molecular iodine-free regioselective 1,2-difunctionalization of olefins and easy access of terminal acetals

Article abstract of DOI:10.1039/c5ra11092k

We have demonstrated a new application of our oxidizing reagent, a combination of NH₂OH·HCl and NaIO₄, in the first generalized regioselective 1,2-difunctionalization of olefins. It is a general method for the preparation of β-iodo-β′-hydroxy ethers, β-iodo ethers, β-iodohydrin, and β-iodo acetoxy compounds using different reaction media. The reactions are highly regioselective, always affording Markovnikov's type addition products. The methodology is also applicable for the easy access of terminal acetals. Molecular iodine-free synthesis, room temperature reaction conditions, high yields, use of less expensive reagents, mild reaction conditions, broad applicability of nucleophiles, and applicability for gram-scale synthesis are the notable advantages of this present protocol.

Full text of DOI:10.1039/c5ra11092k

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Combination of NH2OH·HCl and NaIO4: An Effective Reagent for Molecular
Iodineꢀfree Regioselective 1,2ꢀDifunctionalization of Olefins and Easy Access
of Terminal Acetals
Nirnita Chakraborty, Sougata Santra, Shrishnu Kumar Kundu, Alakananda Hajra, Grigory V.
Zyryanov, and Adinath Majee*

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DOI: 10.1039/C5RA11092K
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ARTICLE TYPE
Combination of NH2OH·HCl and NaIO4: an effective reagent for
molecular iodineꢀfree regioselective 1,2ꢀdifunctionalization of olefins and
easy access of terminal acetals†
Nirnita Chakraborty,a Sougata Santra,b Shrishnu Kumar Kundu,c Alakananda Hajra,a Grigory V.
5
Zyryanov,b,d and Adinath Majee*a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
We have demonstrated a new application of our oxidizing reagent, combination of NH2OH·HCl and
NaIO4, in the first generalized regioselective 1,2ꢀdifunctionalization of olefins. It is a general method for
10 the preparation of βꢀiodoꢀβʹꢀhydroxy ethers, βꢀiodo ethers, βꢀiodohydrin, and βꢀiodo acetoxy compounds
using different reaction media. The reactions are highly regioselective; always afford Markovnikov's type
addition products. The methodology is also applicable for the easy access of terminal acetals. Molecular
iodineꢀfree synthesis, room temperature reaction conditions, high yields, use of less expensive reagents,
mild reaction conditions, broad applicability of nucleophiles, and applicable for gramꢀscale synthesis are
15 the notable advantages of this present protocol.
opening to halohydrins.11 The main disadvantage of the
methodologies for synthesis of halohydrins is to synthesize the
epoxide first by employing the traditional methodologies like the
reaction of alkenes with peracids/bases,12 O2 or H2O2 using a
50 metalꢀbased catalytic system13 or zeolites,14 H2O2/auxiliaries
(nitriles, carbodiimides, etc.).15 Few methodologies have also
been reported for the preparation of halohydrin compounds using
mild reaction conditions with limited nucleophiles.16
Introduction
Reaction of alkenes mainly difunctionalization is a finest
approach adopted in organic synthesis. It has been widely studied
and utilized in various techniques for functional groups
20 interconversions.1 Among them the halohydrin, βꢀiodo ether and
βꢀiodo acetoxy compounds play a crucial role in the field of drug
scaffolds, synthetic organic chemistry, medicinal and industrial
chemistry as well as material sciences.2 They are also the key
intermediates in the synthesis of several halogenated marine
25 natural products.2 The vicinal dihaloalkanes are formed by the
electrophilic halogenation of alkenes.3 When the halogenation of
the alkene is carried out in a nucleophilic solvent such as water,
alcohols, carboxylic acids, nitriles, etc., difunctionalized products
like halohydrins, βꢀhaloethers, βꢀhaloesters, etc. are obtained.
30 This process is known as ‘cohalogenation’ and this is very
important strategy to provide useful products for diverse synthetic
applications.4
βꢀIodo ethers are important intermediates for stereoselective
55 radical reactions17 as well as synthesis of Eꢀ or Zꢀalkenes with
good to moderate diastereoselectivity.18
A
number of
methodologies for the synthesis of this important framework has
been developed by various groups. Among these the most
important approaches are the reactions of alkenes with
60 I(py)2BF4,19 excess amount of iodine,20 diacetoxyiodine(I)
complexes,21 I2/clays,22 I2/ultrasound,23 Nꢀhaloimides,24 Nꢀ
halosaccharin,25 Nꢀiodosuccinimide/alcohols,26 triiodoisocyanuric
acid27 and IBXꢀI2.28
Regardless of their efficiency and reliability, most of these
65 methods suffer from one or more of these disadvantages such as
using expensive reagents and catalysts, long reaction times,
requirement of inert atmosphere, harsh reaction conditions and
mostly use of molecular iodine as iodo source. Although
molecular iodine is a versatile reagent in organic synthesis; it is
70 highly corrosive, toxic, and sublimable, making its use somewhat
unattractive.29 Again, it is important to note that all these
methods8ꢀ28 are not general for the preparation of halohydrin, βꢀ
iodo ether and βꢀiodo acetoxy compounds using the same
reaction conditions; varying the nucleophilic medium like water,
75 alcohol, carboxylic acid etc. respectively. Therefore, finding a
general and efficient methodology for the synthesis of
iodohydrins and βꢀiodo ethers in terms of using basic chemicals
The formation of halohydrins from alkenes is
a wellꢀ
established method.5 On the other hand, halohydrins are also
35 useful intermediates in epoxide synthesis in both laboratory and
industrial scales.6 The formation of chlorohydrins and
bromohydrins by the reaction of alkenes and dilute aqueous
solutions of the halogens undergoes smoothly7 but the formation
of iodohydrins is not so smooth because of the reversibility of the
40 addition of iodine to the double bond. An iodide ion scavenger
9
such as AgNO3, HgO,8 CuO·HBF4 or an oxidizing agent10 is
essential for the formation of iodohydrins. The ringꢀopening of
epoxides by hydrogen halides is also the most common procedure
for the preparation of halohydrins. Hydrogen halides and
45 hypohaliteꢀwater are the conventional reagents for epoxide ring
This journal is © The Royal Society of Chemistry [year]
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Table 1 Substrate scopes to synthesize βꢀiodoꢀβʹꢀhydroxy ethersa
as starting materials, increasing efficiency, operational simplicity,
mild reaction conditions, and economic practicability is highly
desirable.
Entry
1
Substrates (1)
Products (2)
Yields (%)b
OH
O
In continuation of our research in organic synthesis30 herein,
we report a mild and efficient approach for the regioselective
synthesis of various βꢀiodoꢀβʹꢀhydroxy ethers, βꢀiodo ethers,
iodohydrins, and βꢀiodo acetoxy compounds from alkenes using
the combination of NaIO4 and NH2OH·HCl at room temperature
within a short reaction time (Scheme 1, b). Recently we have
I
2a
OH
87, 80c
5
1a
O
Me
2
3
4
2b
2c
2d
83
81
87
Me
Me
I
Me
O
1b
10 reported a mild and efficient approach for oxidation of alcohols to
corresponding carbonyl compounds (Scheme 1, a).31 Based on
this report we can suggest that the in situ generated iodine
undergoes the addition to the double bond to form iodonium ion
which in presence of nucleophilic solvents like alcohols, water,
15 carboxylic acids etc. might afford the corresponding βꢀiodoꢀβʹꢀ
hydroxy ether, βꢀiodo ethers, iodohydrins, and βꢀiodo acetoxy
compounds.
OH
I
MeO
1c
MeO
OH
O
I
1d
Br
Br
OH
O
(a) Our previous approach:
I
5
6
2e
2f
86
81
Cl
1e
O
NH2OH HCl (1.5 equiv)
OH
R2
Cl
R1 R2
R1
OH
NaIO4 (1 equiv), DCM (2 mL)
O
I
Proposed equation for in situ generation of iodine:
1f
NO2
6NaIO4 + 14NH2OH HCl
3I2 + 14NO + 24H2O + 6NaCl + 8HCl
NO2
OH
O
(b) This work:
7
8
I
2g
2h
80
1g
OH
O
NaIO4 (1 equiv)
O
I
I
NH2OH HCl (1.5 equiv)
OH
82d
ethylene glycol (3 mL)
30 min, rt
1h
2a
1a
O
80d
85
OH
9
2i
2j
I
20 Scheme 1 Reaction of styrene with ethylene glycol to synthesize βꢀiodoꢀ
βʹꢀhydroxy ether.
1i
OH
OH
O
OH
10
Results and discussion
1j
I
OH
During our initial study, readily available styrene 1a was taken as
a model substrate using NaIO4 (2 equiv) and NH2OH·HCl (4
25 equiv) as reagent in ethylene glycol solvent. The reaction
proceeded smoothly at room temperature and the product 2ꢀ(2ꢀ
iodoꢀ1ꢀphenylethoxy)ethanol (2a) was isolated in 86% yield
within 30 min. Encouraged by this result our attention was
focused on the optimization of the reagents ratios. First of all, we
30 used 1:1 proportion of NaIO4 and NH2OH.HCl and 68% of
desired product (2a) was observed. By increasing the proportion
of NH2OH.HCl from 1 to 1.5, the desired product (2a) was
increased to 87% yield. The maximum amount of yield was
obtained by using 1:1.5 ratios of NaIO4 and NH2OH.HCl
35 respectively. Further increasing the amount of both the reagents
the yield of the product did not improve significantly.
Me
Ph
O
Me
Ph
11
12
2k
2l
82
81
Ph
Ph
1k
1l
I
OH
O
Ph
Ph
I
a All reactions were performed on a 1 mmol scale in presence of NaIO4 (1
mmol) and NH2OH·HCl (1.5 mmol) in 3 mL of ethylene glycol at room
b
c
40 temperature for 30 min. Isolated yields. styrene 1a (10 mmol), NaIO4
(10 mmol), NH2OH.HCl (15 mmol) in 30 mL of ethylene glycol at room
temperature for 30 min. d cis product.
After optimizing the reaction conditions the scope and
limitations of this reaction were investigated (Table 1). Our
45 attention was focused on the use of different olefinic systems to
prove the general applicability of the reaction conditions. It was
observed that electronꢀrich and electronꢀdeficient styrenes reacted
efficiently with ethylene glycol to afford the desired products
with good yields under the present reaction conditions. The
50 styrene containing an electron donating Me & OMe group on the
aromatic ring showed good efficiency (2b & 2c). The bromoꢀ and
chloroꢀsubstituted styrenes gave the corresponding 2d and 2e in
87% and 86% yields respectively without forming any
2
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Table 2 Substrate scopes using ethanola
dehalogenated products. Other electron withdrawing substituent
NO2 group on styrene moiety afforded the desired product with
satisfactory yield (2f). In addition, aliphatic olefinic systems were
also found to afford the desired products with high yields (2gꢀ2i).
Our present protocol is also effective for cinnamyl alcohol to
produce the corresponding βꢀiodoꢀβʹꢀhydroxy ether (2j). We are
pleased to notice that αꢀmethyl styrene and 1,1ꢀdiphenylethylene
both gave the desired products (2k & 2l) with good yields under
the stated reaction conditions. However, sodium 4ꢀvinyl
10 benzenesulfonate, βꢀmethylꢀβꢀnitrostyrene, and cholesterol did
not give the corresponding iodoethers under the present reaction
conditions. This methodology is also applicable on a gramꢀscale
synthesis. We have successfully prepared the iodoether 2a in 80%
yield by the reaction of styrene (1a, 10 mmol) in ethylene glycol.
15 In general, all the reactions were clean and βꢀiodoꢀβʹꢀhydroxy
ethers were found to be furnished regioselectively in all cases.
Next, we explored our present methodology using ethanol as
other nucleophilic solvent to react with olefinic systems to
synthesize various βꢀiodo ethers (Scheme 2). To our delight the
20 corresponding βꢀiodo ethers (3) were obtained regioselectively in
good yields; the results are summarized in Table 2.
Entry
1
Substrates (
1
)
Products (
3
)
Yieldsb (%)
O
I
3a
3b
3c
3d
86
81
83
85
5
1a
O
I
2
3
4
MeO
Cl
1c
MeO
O
I
1e
Cl
O
OH
OH
1j
I
O
O
Me
Ph
Me
Ph
Ph
5
6
7
3e
3f
83
80
78
Ph
Ph
1k
I
I
Ph
1l
1g
O
3g
I
NaIO4 (1 equiv)
O
a All reactions were performed on a 1 mmol scale in presence of NaIO4 (1
mmol) and NH2OH·HCl (1.5 mmol) in 3 mL of ethanol at room
40 temperature for 30 min. b Isolated yields.
NH2OH HCl (1.5 equiv)
I
Ethanol (3 mL)
30 min, rt
3a
General applicability of the methodology has further been
established by using the different solvents (nucleophiles) for the
synthesis of iodohydrin and βꢀiodoacetoxy compounds (Scheme
3). We have successfully used water and acetic acid to synthesize
45 iodohydrin (4) and βꢀiodoacetoxy compounds (5) with good
yields which increases the scope of this transformation. It is
worthy to mention that a little amount of THF was added to water
as solvent to synthesize the iodohydrins. The styrene, substituted
with chloroꢀ and nitroꢀsubstituent smoothly affored the desired
50 products (4a, 4b, 4c, 5a & 5b). We are delighted to inform that αꢀ
methyl styrene and 1,1ꢀdiphenylethylene both reacted well to
give the corresponding iodohydrins (4d & 4e). Aliphatic olefins
such as 1ꢀoctene, cyclohexene and cyclooctene can also afford
the desired iodohydrins (4fꢀ4h) with good yields. However, βꢀ
55 methylꢀβꢀnitrostyrene did not give the corresponding iodohydrin
under this present reaction conditions.
1a
Scheme 2 Synthesis of βꢀiodo ether using ethanol.
Simple styrene reacted well to give the desired βꢀiodo ether
25 with high yield (3a). Styrenes substituted by electron donating
OMe group (3b) as well as electron withdrawing halogen group
(3c) underwent smooth reactions which highlighted the wide
scope of this reaction. Meanwhile, the effect of alcoholic group in
the olefinic system also investigated. Cinnamyl alcohol can also
30 afford the desired product with excellent yield (3d). αꢀMethyl
styrene and 1,1ꢀdiphenylethylene also nicely participated in the
reaction, yielding the corresponding products 3e and 3f in 83%
and 80% yields respectively. Moreover, aliphatic alkene such as
1ꢀoctene also afforded the desired product (3g) with good yield
35 which also proves the general applicability of this present
protocol.
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NaIO4 (1 equiv)
HCl (1.5equiv)
instead of aldehydes as substrate is a demanding task. Very few
methods are available in literature using palladium,32 iron33 and a
couple of nonmetal catalyzed methods.34 Recently, Narender et
al. reported a metalꢀfree approach for the synthesis of terminal
20 acetals by tandem oxidative rearrangement of olefins using oxone
as an oxidant in the presence of iodine.35 It is noteworthy to
mention that our synthesized compound 2 is the key intermediate
for synthesizing the terminal acetals. After successive reaction
with βꢀiodoꢀβʹꢀhydroxy ethers (2) using oxone as oxidant, various
25 terminal acetals (6aꢀ6j) were successfully synthesized by
employing the reported method (Scheme 5).35
OH
I
NH2OH
R
R
Water/THF (2.5/0.5 mL)
30 min, rt
4
1
OH
OH
OH
H3C OH
I
I
I
I
Cl
NO2
4c, 81%
4d, 80%
4a, 83%
4b, 84%
I
HO
OH
I
OH
I
OH
Oxone
O
I
O
R
I
OH
O
ethylene glycol
2 h, rt
R
2
6
R = aryl, alkyl
4g, 76%
4e, 81%
4f, 78%
NaIO4 (1 equiv)
4h, 70%
O
O
O
O
O
O
O
O
Cl
MeO
OAc
I
NH2OH HCl (1.5 equiv)
6d, 93%
6b, 71%
6a, 72%
6c, 94%
R
R
Acetic acid (3 mL)
30 min, rt
O
O
O
O
5
1
O
O
6e, 80%
6f, 91%
6g, 81%
OAc
OAc
I
I
OH
Oxone
O
O
Cl
O
OH
OH ethylene glycol
2 h, rt
5b, 82%
5a, 79%
I
Scheme 3 Synthesis of iodohydrin and βꢀiodoacetoxy compounds.
6h, 84%
2i
Next we have examined the possibility of intramolecular
cyclization reaction under the present reaction conditions
(Scheme 4). We have found that cinnamyl alcohol (1j) gave no
reaction either oxidation31 to aldehyde or the intramolecular
reaction by nucleophilic attack of alcoholic oxygen when the
reaction has been carried out in non coordinating solvent like
toluene. But it is worthy to mention that other homoallylic
OH
Oxone
R
O
O
R
Ph
5
ethylene glycol
2 h, rt
Ph
I
O
2j
Me
Ph
O
O
Ph
Ph
10 alcohols like 1m and 1n gave the cyclization products (7a, 7a′,
7b and 7b′) in presence of toluene or ethylene glycol. We have
got inseparable mixture of products with good yields.
O
O
6j, 85%
6i, 74%
Scheme 5 Synthesis of terminal acetals from βꢀiodoꢀβʹꢀhydroxy ethers.
NaIO4 (1 equiv)
NH2OH HCl (1.5 equiv)
Ph
OH
No Reaction
30 Conclusions
Toluene
1 h, rt
1j
In summary, we have developed a simple and general method for
the synthesis of βꢀiodoꢀβʹꢀhydroxy ether, βꢀiodo ether, βꢀiodo
hydrin, and βꢀiodo acetoxy compounds using the combination of
NH2OH·HCl and NaIO4 as iodine source at room temperature
35 within a short reaction time using different solvents which act as
nucleophiles. Furthermore, the βꢀiodoꢀβʹꢀhydroxy ethers have
been converted to terminal acetals using the reported method by
using oxone as oxidant. The preparation of terminal acetals using
βꢀiodoꢀβʹꢀhydroxy ether is the very important functionalization of
40 alkene as we can functionalize the germinal position by nonꢀ
Wacker reaction. The advantages of this present protocol are: (i)
molecular iodineꢀfree synthesis, (ii) room temperature and mild
reaction conditions, (iii) short reaction time, (iv) high yields, (v)
use of less expensive reagents, (vi) applicable for broad solvent
45 (nucleophile) systems, and (vii) applicable for gramꢀscale
synthesis. These advantages render this protocol facile and
suitable to create a diversified library of βꢀiodoꢀβʹꢀhydroxy ether,
NaIO4 (1 equiv)
I
I
NH2OH HCl (1.5 equiv)
+
O
7a
OH
O
Solvent
1 h, rt
1m
7a'
Solvent: Toluene, ethylene glycol
(92% Yield)
NaIO4 (1 equiv)
I
I
Ph
OH
NH2OH HCl (1.5 equiv)
+
O
Solvent
1 h, rt
Ph
O
Ph
1n
7b
7b'
Solvent: Toluene, ethylene glycol
(80% Yield)
Scheme 4 Additional experiments on intramolecular cyclization reaction.
15
Preparation of acetals at the terminal position of alkenes
4
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βꢀiodo ether, βꢀiodo hydrin, and βꢀiodo acetoxy compounds.
2ꢀ(1ꢀ(2,4ꢀdimethylphenyl)ꢀ2ꢀiodoethoxy)ethanol (2b). 275 mg,
1
yield 83%, yellow liquid; H NMR (400 MHz, CDCl3): δ 7.18
Experimental Section
(d, J = 7.6 Hz,1H), 6.95 (d, J = 8 Hz, 1H), 6.89 (s, 1H), 4.58 (t, J
General experimental methods
60 = 6.4 Hz,1H), 3.66 ꢀ 3.64 (m, 2H), 3.47ꢀ3.43 (m, 1H), 3.33 ꢀ 3.28
1H NMR spectra were determined on a Bruker 400 (400 MHz)
spectrometer as solutions in CDCl3. Chemical shifts are
expressed in parts per million (δ) and are referenced to
tetramethylsilane (TMS) as internal standard and the signals were
reported as s (singlet), d (doublet), t (triplet), m (multiplet) and
coupling constants J were given in Hz. 13C NMR spectra were
10 recorded at 100 MHz in CDCl3 solution. TLC was done on silica
gel coated glass slide (Merck, Silica gel G for TLC). Silica gel
(60ꢀ120 mesh, SRL, India) was used for column chromatography.
(m, 1H), 3.20 (d, J = 6.8 Hz, 2H), 2.47 (br, 1H), 2.21 (s, 6H) ; 13
C
5
NMR (100 MHz, CDCl3): δ 137.9, 135.2, 134.7, 131.6, 127.3,
125.5, 79.1, 70.7, 61.8, 21.1, 19.0, 10.0 Anal. calcd for
C12H17IO2: C, 45.02; H, 5.35 %; Found: C, 44.98; H, 5.30%.
65
2ꢀ(2ꢀIodoꢀ1ꢀ(4ꢀmethoxyphenyl)ethoxy)ethanol (2c). 261 mg,
yield 81%, yellow liquid; 1H NMR (CDCl3, 400 MHz): δ 7.16 (d,
J = 8.4 Hz, 2H), 6.83 (d, J = 8.4 Hz, 2H), 4.36ꢀ4.33 (m, 1H), 3.74
(s, 3H), 3.71ꢀ3.66 (m, 2H), 3.49ꢀ3.44 (m, 1H), 3.37ꢀ3.21(m, 3H),
Petroleum ether refers to the fraction boiling in the range of 60ꢀ 70 2.25 (br, 1H); 13C NMR (CDCl3, 100 MHz): δ 159.9, 131.7,
80 ºC unless otherwise mentioned. Melting points were
15 determined on a glass disk with an electric hot plate and are
uncorrected. All solvents were dried and distilled before use.
Commercially available substrates were freshly distilled before
127.7, 114.3, 82.0, 70.6, 61.9, 55.4, 11.3. Anal. calcd for
C11H15IO3: C, 41.01; H, 4.69%; Found: C, 40.95; H, 4.67%.
2ꢀ(1ꢀ(3ꢀBromophenyl)ꢀ2ꢀiodoethoxy)ethanol (2d). 323 mg,
1
the reaction. Solvents, reagents and chemicals were purchased 75 yield 87%, yellow liquid; H NMR (CDCl3, 400 MHz): δ 7.47ꢀ
from Aldrich, Fluka, Merck, SRL, Spectrochem and Process
20 Chemicals. All reactions involving moisture sensitive reactants
were executed using oven dried glassware.
7.44 (m, 2H), 7.25ꢀ7.21 (m, 2H), 4.43ꢀ4.40 (m,1H), 3.76ꢀ3.74 (m,
2H), 3.57ꢀ3.52 (m, 1H), 3.47ꢀ3.42 (m, 1H), 3.37ꢀ3.29 (m, 2H),
2.59 (br, 1H); 13C NMR (CDCl3, 100 MHz): δ 142.1, 131.7,
130.4, 129.5, 125.1, 122.9, 81.6, 71.0, 61.7, 10.3. Anal. calcd for
80 C10H12BrIO2: C, 32.37; H, 3.26%; Found: C, 32.32; H, 3.21%.
Typical procedure for the synthesis of compound 2
A mixture of alkene (1 mmol), NaIO4 (1 mmol, 213 mg) in 3 mL
of ethylene glycol was taken in a round bottomed flask at room
25 temperature and then NH2OH·HCl (1.5 mmol, 104 mg) was
added by portion for 5 min. The reaction mixture was stirred for
30 min at room temperature. After completion (TLC), the
reaction mixture was diluted with a 1:1 mixture of water/ethyl
acetate (10 mL) and washed with 10% (w/v) Na2S2O3 (3x5 mL)
30 followed by brine solution (1x10 mL). Then the combined
organic layer was dried over anhydrous Na2SO4. Evaporation of
solvent furnished the crude product which was subjected to
column chromatography using ethyl acetateꢀpetroleum ether
(1:15) as eluent to obtain the analytically pure product.
2ꢀ(1ꢀ(4ꢀChlorophenyl)ꢀ2ꢀiodoethoxy)ethanol (2e). 281 mg,
yield 86%, yellow liquid; H NMR (CDCl3, 400 MHz): δ 7.37ꢀ
1
7.34 (m, 2H), 7.28ꢀ7.26 (m, 2H), 4.46ꢀ4.43 (m, 1H), 3.76 (t, J =
85 4.4 Hz, 2H), 3.57ꢀ3.53 (m, 1H), 3.48ꢀ3.43 (m, 1H), 3.39ꢀ3.30 (m,
2H), 2.43 (br, 1H); 13C NMR (CDCl3, 100 MHz): δ 138.3, 134.4,
129.1, 127.9, 81.6, 70.9, 61.8, 10.4. Anal. calcd for C10H12ClIO2:
C, 36.78; H, 3.70%; Found: C, 36.73; H, 3.62.%
90 2ꢀ(2ꢀIodoꢀ1ꢀ(3ꢀnitrophenyl)ethoxy)ethanol (2f). 273 mg, yield
81%, yellow liquid; 1H NMR (CDCl3, 400 MHz): δ 8.23ꢀ8.21 (m,
2H), 7.71 (d, J = 8 Hz, 1H), 7.62ꢀ7.57 (m, 1H), 4.60ꢀ4.57 (m,
1H), 3.81 (s, 2H), 3.62ꢀ3.51 (m, 2H), 3.44ꢀ3.37 (m, 2H), 2.32 (br,
1H); 13C NMR (CDCl3, 100 MHz): δ 148.7, 142.2, 132.6, 130.0,
95 123.7, 121.7, 81.2, 71.3, 61.9, 9.7. Anal. calcd for C10H12INO4:
C, 35.63; H, 3.59; N, 4.15%; Found: C, 35.56; H, 3.53; N, 4.11%.
35 Typical procedure for the synthesis of compound 2a on gramꢀ
scale
A mixture of styrene 1a (10 mmol, 1.04 g), NaIO4 (10 mmol,
2.13 g) in 30 mL of ethylene glycol was taken in a round
bottomed flask at room temperature and then NH2OH·HCl (15
40 mmol, 1.04 g) was added by portion for 5ꢀ10 min. The reaction
mixture was stirred for 30 min at room temperature. After
completion (TLC), the reaction mixture was diluted with a 1:1
mixture of water/ethyl acetate (50 mL) and washed with 10%
(w/v) Na2S2O3 (3x20 mL) followed by brine solution (1x30 mL).
45 Then the combined organic layer was dried over anhydrous
Na2SO4. Evaporation of solvent furnished the crude product
which was subjected to column chromatography using ethyl
acetateꢀpetroleum ether (1:15) as eluent to obtain the analytically
pure product.
50 2ꢀ(2ꢀIodoꢀ1ꢀphenylethoxy)ethanol (2a). 254 mg, yield 87%
(2.34 g, 80% yield for 10 mmol), yellow liquid; 1H NMR (CDCl3,
400 MHz): δ 7.28ꢀ7.22 (m, 5H), 4.39ꢀ4.36 (m, 1H), 3.66 (s, 2H),
3.48ꢀ3.24 (m, 4H), 2.47 (br, 1H); 13C NMR (CDCl3, 100 MHz): δ
139.7, 128.8, 128.6, 126.4, 82.3, 70.7, 61.7, 11.0. Anal. calcd for
55 C10H13IO2: C, 41.12; H, 4.49%; Found: C, 41.08; H, 4.46%.
2ꢀ(1ꢀIodooctanꢀ2ꢀyloxy)ethanol (2g). 240 mg, yield 80%, yellow
1
liquid; H NMR (CDCl3, 400 MHz): δ 3.77ꢀ3.56 (m, 4H), 3.36ꢀ
100 3.31 (m, 1H), 3.28ꢀ3.20 (m, 1H), 2.23 (br, 1H), 1.81ꢀ1.73 (m,
1H), 1.65ꢀ1.55 (m, 2H), 1.40ꢀ1.30 (m, 8H), 0.92ꢀ0.85 (m, 3H);
13C NMR (CDCl3, 100 MHz): δ 78.9, 70.6, 62.1, 34.7, 31.8, 29.3,
25.3, 22.7, 14.2, 10.6. Anal. calcd for C10H21IO2: C, 40.01; H,
7.05%; Found: C, 39.98; H, 7.01%.
105
2ꢀ(2ꢀIodocyclohexyloxy)ethanol (2h). 221 mg, yield 82%,
1
yellow liquid; H NMR (CDCl3, 400 MHz): δ 4.01ꢀ3.95 (m, 1H),
3.72ꢀ3.67 (m, 3H), 3.48ꢀ3.44 (m, 1H), 3.30ꢀ3.24 (m, 1H), 2.41ꢀ
2.36 (m, 1H), 2.11ꢀ2.07 (m, 1H), 2.01ꢀ1.89 (m, 1H), 1.80ꢀ1.76
110 (m, 1H), 1.50ꢀ1.46 (m, 1H), 1.31ꢀ1.22 (m, 4H); 13C NMR
(CDCl3, 100 MHz): δ 83.3, 70.5, 62.0, 38.7, 36.5, 31.8, 27.9,
24.1. Anal. calcd for C8H15IO2: C, 35.57; H, 5.60%; Found C,
35.53; H, 5.56%.
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2ꢀ(2ꢀIodocyclooctyloxy)ethanol (2i). 238 mg, yield 80%, yellow 60 1ꢀChloroꢀ4ꢀ(1ꢀethoxyꢀ2ꢀiodoethyl)benzene (3c). 257 mg, yield
1
1
liquid; H NMR (CDCl3, 400 MHz): δ 4.33ꢀ4.28 (m, 1H), 3.69ꢀ
83%, orange liquid; H NMR (CDCl3, 400 MHz): δ 7.33 (d, J =
3.62 (m, 4H), 3.37ꢀ3.33 (m, 1H), 2.11ꢀ1.56 (m, 9H), 1.32ꢀ1.25
(m, 4H); 13C NMR (CDCl3, 100 MHz): δ 87.0, 70.5, 61.9, 42.8,
33.2, 30.6, 27.2, 26.7, 25.8, 25.3. Anal. calcd for C10H19IO2: C,
40.28; H, 6.42%; Found: C, 40.22; H, 6.34%.
8.4 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), 4.38ꢀ4.35 (m, 1H), 3.45ꢀ
3.40 (m, 2H), 3.34ꢀ3.26 (m, 2H), 1.21 (t, J = 7.2 Hz, 3H); 13C
NMR (CDCl3, 100 MHz): δ 139.2, 134.1, 128.9, 128.0, 81.2,
65 65.3, 15.3, 10.5. Anal. calcd for C10H12ClIO: C, 38.67; H, 3.89%;
Found: C, 38.61; H, 3.82%.
5
3ꢀ(2ꢀHydroxyethoxy)ꢀ2ꢀiodoꢀ3ꢀphenylpropanꢀ1ꢀol (2j). 274
1
10 mg, yield 85%, yellow liquid; H NMR (CDCl3, 400 MHz): δ
3ꢀEthoxyꢀ2ꢀiodoꢀ3ꢀphenylpropanꢀ1ꢀol (3d). 260 mg, yield 85%,
yellow liquid; H NMR (CDCl3, 400 MHz): δ 7.35ꢀ7.31 (m, 5H),
1
7.40ꢀ7.31 (m, 5H), 4.69 (d, J = 7.6 Hz, 1H), 4.39ꢀ4.35 (m, 1H),
4.19ꢀ4.11 (m, 1H), 3.93ꢀ3.81 (m, 1H), 3.74 (s, 2H), 3.60ꢀ3.29 (m, 70 4.62 (d, J = 7.2 Hz, 1H), 4.35ꢀ4.31 (m, 1H), 3.99ꢀ3.95 (m, 1H),
2H), 3.18 (br, 2H); 13C NMR (CDCl3, 100 MHz): δ 138.9, 128.7,
128.6, 127.6, 85.1, 70.9, 65.8, 61.7, 39.7. Anal. calcd for
15 C11H15IO3: C, 41.01; H, 4.69%; Found: C, 40.97; H, 4.63%.
3.84ꢀ3.80 (m, 1H), 3.43ꢀ3.38 (m, 2H), 3.11 (br, 1H), 1.18 (t, J =
7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz): δ 139.4, 128.6, 128.5,
127.5, 86.4, 66.5, 65.6, 39.1, 15.3. Anal. calcd for C11H15IO2: C,
43.16; H, 4.94%; Found: C, 43.13; H, 4.90%.
2ꢀ(1ꢀIodoꢀ2ꢀphenylpropanꢀ2ꢀyloxy)ethanol (2k). 251 mg, yield
82%, yellow liquid; 1H NMR (CDCl3, 400 MHz): δ 7.44ꢀ7.32 (m,
5H), 3.80ꢀ3.74 (m, 2H), 3.57 (d, J = 10.8 Hz,1H), 3.49ꢀ3.40 (m,
20 2H), 3.33ꢀ3.29 (m, 1H), 2.37 (br, 1H), 1.76 (s, 3H); 13C NMR
(CDCl3, 100 MHz): δ 141.4, 128.7, 128.0, 126.2, 76.5, 64.3, 62.2,
75
1ꢀ(2ꢀEthoxyꢀ1ꢀiodopropanꢀ2ꢀyl)benzene (3e).20 241 mg, yield
83%, orange liquid; 1H NMR (CDCl3, 400 MHz): δ 7.42ꢀ7.25 (m,
5H), 3.53ꢀ3.45 (m, 2H), 3.36ꢀ3.32 (m, 1H), 3.24ꢀ3.18 (m, 1H),
1.70 (s, 1H), 1.23ꢀ1.19 (m, 3H); 13C NMR (CDCl3, 100 MHz): δ
24.5, 20.3. Anal. calcd for C11H15IO2: C, 43.16; H, 4.94%; 80 142.4, 128.5, 127.7, 126.3, 76.7, 58.9, 24.8, 20.0, 15.7.
Found: C, 43.12; H, 4.91%.
1ꢀEthoxyꢀ2ꢀiodoꢀ1,1ꢀdiphenylethane (3f). 262 mg, yield 80%,
1
25 2ꢀ(2ꢀIodoꢀ1,1ꢀdiphenylethoxy)ethanol (2l). 298 mg, yield 81%,
pale yellow solid, mp 70ꢀ72 °C; H NMR (CDCl3, 400 MHz): δ
pale orange solid, mp 67ꢀ68 °C; H NMR (CDCl3, 400 MHz): δ
1
7.38ꢀ7.18 (m, 10H), 4.10 (s, 2H), 3.22 (q, J = 7.2 Hz, 2H), 1.25 (t,
7.40ꢀ7.25 (m, 10H), 4.18 (s, 2H), 3.84 (t, J = 4.4 Hz, 2H), 3.32 (t, 85 J = 6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz): δ 143.5, 128.5,
J = 4.4 Hz, 2H), 2.21 (br, 1H); 13C NMR (CDCl3, 100 MHz): δ
142.9, 128.3, 127.6, 127.1, 80.2, 64.0, 62.3, 16.8. Anal. calcd for
30 C16H17IO2: C, 52.19; H, 4.65%; Found: C, 52.13; H, 4.61%.
128.1, 127.3, 127.1, 127.0, 126.2, 80.2, 57.9, 16.8, 15.4. Anal.
calcd for C16H17IO: C, 54.56; H, 4.86%; Found: C, 54.51; H,
4.82%.
90 2ꢀEthoxyꢀ1ꢀiodooctane (3g). 221 mg, yield 78%, pale yellow
liquid; H NMR (CDCl3, 400 MHz): δ 3.59ꢀ3.36 (m, 2H), 3.20ꢀ
Typical procedure for the synthesis of compound 3
1
A mixture of alkene (1 mmol), NaIO4 (1 mmol, 213 mg) in 3 mL
of ethanol was taken in a round bottomed flask at room
35 temperature and then NH2OH·HCl (1.5 mmol, 104 mg) was
added by portion for 5 min. The reaction mixture was stirred for
30 min at room temperature. After completion (TLC), the
reaction mixture was diluted with a 1:1 mixture of water/ethyl
acetate (10 mL) and washed with 10% (w/v) Na2S2O3 (3x5 mL)
40 followed by brine solution (1x10 mL). Then the combined
organic layer was dried over anhydrous Na2SO4. Evaporation of
3.18 (m, 2H), 3.12ꢀ3.07 (m, 1H), 1.56ꢀ1.46 (m, 3H), 1.27ꢀ1.13
(m, 10H), 0.83ꢀ0.80 (m, 3H); 13C NMR (CDCl3, 100 MHz): δ
78.5, 65.1, 34.8, 31.9, 29.3, 25.4, 22.7, 15.6, 14.2, 10.6. Anal.
95 calcd for C10H21IO: C, 42.26; H, 7.45%; Found: C, 42.18; H,
7.36%.
Typical procedure for the synthesis of compound 4
A mixture of alkene (1 mmol), NaIO4 (1 mmol, 213 mg) in a
mixture of 2.5 mL of water and 0.5 mL of THF was taken in a
solvent furnished the crude product which was subjected to 100 round bottomed flask at room temperature and then NH2OH·HCl
column chromatography using ethyl acetateꢀpetroleum ether
(1:15) as eluent to obtain the analytically pure product.
(1.5 mmol, 104 mg) was added by portion for 5 min. The reaction
mixture was stirred for 30 min at room temperature. After
completion (TLC), the reaction mixture was diluted with a 1:1
mixture of water/ethyl acetate (10 mL) and washed with 10%
45
1ꢀ(1ꢀEthoxyꢀ2ꢀiodoethyl)benzene (3a).16g 237 mg, yield 86%,
orange liquid; 1H NMR (CDCl3, 400 MHz): δ 7.42ꢀ7.35 (m, 5H), 105 (w/v) Na2S2O3 (3x5 mL) followed by brine solution (1x10 mL).
4.46ꢀ4.43 (m, 1H), 3.52ꢀ3.44 (m, 2H), 3.41ꢀ3.34 (m, 2H), 1.26 (t,
Then the combined organic layer was dried over anhydrous
Na2SO4. Evaporation of solvent furnished the crude product
which was subjected to column chromatography using ethyl
acetateꢀpetroleum ether (1:15) as eluent to obtain the analytically
J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz): δ 140.6, 128.7,
50 128.3, 126.5, 81.9, 65.1, 15.2, 11.0.
1ꢀ(1ꢀEthoxyꢀ2ꢀiodoethyl)ꢀ4ꢀmethoxybenzene (3b). 248 mg, 110 pure product.
yield 81%, yellowish orange liquid; 1H NMR (CDCl3, 400 MHz):
δ 7.27ꢀ7.23 (m, 2H), 6.91ꢀ6.88 (m, 2H), 4.38ꢀ4.34 (m, 1H), 3.81
55 (s, 3H), 3.46ꢀ3.26 (m, 4H), 1.21 (t, J = 7.2 Hz, 3H); 13C NMR
(CDCl3, 100 MHz): δ 159.8, 159.7, 132.7, 128.1, 127.8, 114.1,
2ꢀIodoꢀ1ꢀphenylethanol (4a).16g 206 mg, yield 83%, pale yellow
liquid; H NMR (CDCl3, 400 MHz): δ 7.40ꢀ7.26 (m, 5H), 4.85ꢀ
1
4.82 (m, 1H), 3.51ꢀ3.48 (m, 1H), 3.43ꢀ3.38 (m, 1H), 2.52 (br,
81.5, 64.9, 64.8, 55.4, 15.3, 15.28, 11.4. Anal. calcd for 115 1H); 13C NMR (CDCl3, 100 MHz): δ 141.3, 128.8, 128.5, 125.9,
C11H15IO2: C, 43.16; H, 4.94%; Found: C, 43.12; H, 4.91%.
74.1, 15.4.
6
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followed by brine solution (1x10 mL). Then the combined
1ꢀ(4ꢀChlorophenyl)ꢀ2ꢀiodoethanol (4b). 237 mg, yield 84%, 60 organic layer was dried over anhydrous Na2SO4. Evaporation of
1
pale yellow solid, mp 67ꢀ69 °C; H NMR (CDCl3, 400 MHz): δ
7.35ꢀ7.29 (m, 4H), 4.81ꢀ4.78 (m, 1H), 3.48ꢀ3.44 (m, 1H), 3.38ꢀ
3.33 (m, 1H), 2.61 (br, 1H); 13C NMR (CDCl3, 100 MHz): δ
139.7, 134.2, 129.0, 127.3, 73.4, 15.1. Anal. calcd for C8H8ClIO:
C, 34.01; H, 2.85%; Found: C, 33.94; H, 2.78%.
solvent furnished the crude product which was subjected to
column chromatography using ethyl acetateꢀpetroleum ether
(1:15) as eluent to obtain the analytically pure product.
5
65 2ꢀIodoꢀ1ꢀphenylethyl acetate (5a).16c 229 mg, yield 79%, yellow
1
liquid; H NMR (CDCl3, 400 MHz): δ 7.38ꢀ7.34 (m, 5H), 5.98ꢀ
2ꢀIodoꢀ1ꢀ(3ꢀnitrophenyl)ethanol (4c). 237 mg, yield 81%, pale
5.86 (m, 1H), 3.82ꢀ3.70 (m, 1H), 3.48ꢀ3.45 (m, 1H), 2.14ꢀ2.13
(m, 3H); 13C NMR (CDCl3, 100 MHz): δ 170.1, 169.9, 138.6,
137.3, 129.0, 128.9, 128.8, 126.8, 126.6, 75.3, 75.2, 46.6, 21.2,
10 orange liquid; 1H NMR (CDCl3, 400 MHz): δ 8.28ꢀ8.22 (m, 2H),
7.73 (d, J = 8 Hz, 1H), 7.60 (t, J = 8 Hz,1H), 5.15 (q, J = 5.2 Hz,
1H), 3.87ꢀ3.83 (m, 1H), 3.71 (t, J = 10.4 Hz, 1H); 13C NMR 70 21.1, 7.9.
(CDCl3, 100 MHz): δ 148.5, 141.3, 133.5, 130.0, 124.1, 122.5,
59.7, 8.9. Anal. calcd for C8H8INO3: C, 32.79; H, 2.75; N, 4.78%;
15 Found: C, 32.72; H, 2.67; N, 4.70%.
1ꢀ(4ꢀChlorophenyl)ꢀ2ꢀiodoethyl acetate (5b). 266 mg, yield
82%, yellow liquid; 1H NMR (CDCl3, 400 MHz): δ 7.36ꢀ7.26 (m,
4H), 5.93ꢀ5.81 (m, 1H), 3.76ꢀ3.70 (m, 1H), 3.45ꢀ3.42 (m, 1H),
1ꢀiodoꢀ2phenylpropanꢀ2ꢀol (4d). 218 mg, yield 80%, pale 75 2.13ꢀ2.13 (m, 3H); 13C NMR (CDCl3, 100 MHz): δ 169.9, 169.8,
1
yellow liquid; H NMR (400 MHz, CDCl3): δ 7.46ꢀ7.20 (m, 5H),
3.70 ꢀ 3.61 (m, 2H), 2.34 (br, 1H), 1.73 (s, 3H) ; 13C NMR (100
20 MHz, CDCl3): δ 144.4, 128.6 (2C), 127.6 (2C), 124.9, 72.8, 29.1,
24.3 Anal. calcd for C9H11IO: C, 41.24; H, 4.34 %; Found: C,
41.26; H, 4.30%.
137.0, 135.8, 134.9, 134.7, 129.0, 128.2, 128.0, 74.5, 74.4, 46.3,
21.1, 21.0, 7.4. Anal. calcd for C10H10ClIO2: C, 37.01; H, 3.11%;
Found: C, 36.97; H, 3.05%.
Typical procedure for the synthesis of compound 635
80 Oxone (0.75 mmol) was slowly added to compound 2 (1 mmol)
in 2 mL of ethylene glycol in a round bottomed flask and the
reaction mixture was stirred at room temperature for 2 h. After
completion (TLC), the reaction mixture was diluted with a 1:1
mixture of water/DCM (10 mL) and washed with 10% (w/v)
85 Na2S2O3 (2x5 mL) followed by brine solution (1x10 mL). Then
the combined organic layer was dried over anhydrous Na2SO4.
Evaporation of solvent furnished the crude product which was
subjected to column chromatography using ethyl acetateꢀ
petroleum ether (1:15) as eluent to obtain the analytically pure
90 product.
2ꢀiodoꢀ1,1ꢀdiphenylethanol (4e). 270 mg, yield 81%, deep
25 yellow liquid; 1H NMR (400 MHz, CDCl3): δ 7.52 (d, J = 7.6 Hz,
4H), 7.42ꢀ7.33 (m, 6H), 4.07 (s, 2H), 2.98 (s, 1H); 13C NMR (100
MHz, CDCl3): δ 143.5 (2C), 128.4 (4C), 127.7 (4C), 126.2 (2C),
76.7, 22.5. Anal. calcd for C14H13IO: C, 51.87; H, 4.04%; Found:
C, 51.83; H, 4.08%.
30
1ꢀiodooctanꢀ2ꢀol (4f). 208 mg, yield 78%, pale yellow liquid; 1H
NMR (400 MHz, CDCl3): δ 3.52 ꢀ 3.50 (m, 1H), 3.41ꢀ 3.38 (m,
1H), 3.25ꢀ3.22 (m, 1H), 1.57 ꢀ 1.25 (m, 11H), 0.88 (t, J = 5.2 Hz,
3H) ; 13C NMR (100 MHz, CDCl3): δ 71.2, 36.8, 31.8, 29.3, 25.8,
35 22.7, 16.9, 14.2. Anal. calcd for C8H17IO: C, 37.51; H, 6.69%;
Found: C, 37.49; H, 6.72%.
2ꢀBenzylꢀ1,3ꢀdioxolane (6a).35 116 mg, yield 71%, red liquid; 1H
NMR (CDCl3, 400 MHz): δ 7.35ꢀ7.21 (m, 5H), 5.07 (t, J = 4.8
Hz, 1H), 3.99ꢀ3.82 (m, 4H), 2.97 (d, J = 4.8 Hz, 2H); 13C NMR
95 (CDCl3, 100 MHz): δ 136.3, 129.8, 128.5, 126.7, 104.8, 65.1,
40.9.
2ꢀiodocyclohexanol (4g). 180 mg, yield 76%, orange gummy
1
mass; H NMR (400 MHz, CDCl3): δ 4.05ꢀ4.00 (m, 1H) 3.70ꢀ
40 3.60 (m, 1H), 2.11ꢀ1.20 (m, 9H), 13C NMR (100 MHz, CDCl3): δ
76.0, 43.4, 38.6, 33.6, 28.0, 24.4. Anal. calcd for C6H11IO: C,
31.88; H,4.90%; Found: C, 31.82; H, 4.96%.
2ꢀ(4ꢀChlorobenzyl)ꢀ1,3ꢀdioxolane (6b).35 158 mg, yield 80%,
1
white solid, mp 38ꢀ40 °C; H NMR (CDCl3, 400 MHz): δ 7.28ꢀ
100 7.18 (m, 4H), 5.04 (t, J = 4.8 Hz, 1H), 3.94ꢀ3.82 (m, 4H), 2.93 (d,
J = 4.8 Hz, 2H); 13C NMR (CDCl3, 100 MHz): δ 134.6, 132.6,
131.2, 128.5, 104.4, 65.2, 40.2.
2ꢀiodocyclooctanol (4h). 184 mg, yield 70%, gummy brown
1
45 liquid; H NMR (400 MHz, CDCl3): δ 4.42ꢀ4.38 (m, 1H), 4.03ꢀ
3.98 (m, 1H), 2.21ꢀ1.90 (m, 6H), 1.65ꢀ1.44 (m, 7H) ; 13C NMR
2ꢀ(2,4ꢀDimethylbenzyl)ꢀ1,3ꢀdioxolane (6c). 180 mg, yield 94%,
105 pale orange liquid; H NMR (CDCl3, 400 MHz): δ 7.39 (d, J =
(100 MHz, CDCl3): δ 78.4, 50.5, 34.4, 32.5, 27.0, 26.0, 25.7,
25.5. Anal. calcd for C8H15IO: C, 37.81; H, 5.95%; Found: C,
1
7.5 Hz, 1H), 7.24ꢀ7.22 (m, 2H), 5.30 ( t, J = 5 Hz, 1H), 4.21( t,
J = 6.5 Hz, 2H), 4.08 (t, J = 6.5 Hz, 2H), 3.22 (d, J = 5 Hz, 2H),
2.59 (s, 3H), 2.55 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 136.4,
136.0, 131.3, 130.8, 130.1, 126.4, 104.3 (2C), 64.7, 37.3, 20.8,
37.83; H, 5.91%.
50
Typical procedure for the synthesis of compound 5
A mixture of alkene (1 mmol), NaIO4 (1 mmol, 213 mg) in 3 mL 110 19.6. Anal. calcd for C12H16O2: C, 74.97; H, 8.39%; Found: C,
of acetic acid was taken in a round bottomed flask at room
temperature and then NH2OH·HCl (1.5 mmol, 104 mg) was
55 added by portion for 5 min. The reaction mixture was stirred for
30 min at room temperature. After completion (TLC), the
74.95; H, 8.41%.
2ꢀ(4ꢀMethoxybenzyl)ꢀ1,3ꢀdioxolane (6d).35 180 mg, yield 93%,
pale yellow liquid; H NMR (CDCl3, 400 MHz): δ 7.12ꢀ7.10 (m,
1
reaction mixture was diluted with a 1:1 mixture of water/ethyl 115 2H), 6.78 – 6.75 (m, 2H), 4.94 (t, J = 4.8 Hz, 1H) 3.87ꢀ3.73 (m,
acetate (10 mL) and washed with 10% (w/v) Na2S2O3 (3x5 mL)
4H), 3.70 (s, 3H) 2.83 (d, J = 4.8 Hz, 2H); 13C NMR (CDCl3, 100
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MHz): δ 158.4, 130.7 (2C), 128.3, 113.9 (2C), 104.9 (2C), 65.0,
55.3, 39.9.
Inseparable mixture, 182 mg, yield 92%, colorless liquid; 1H
60 NMR (CDCl3, 400 MHz): δ 4.78ꢀ4.41 (m, 1H), 4.24ꢀ4.18 (m,
1H), 4.11ꢀ4.07 (m, 1H), 3.92ꢀ3.83 (m, 4H), 3.79ꢀ3.76 (m, 1H),
3.66ꢀ3.62 (m, 1H), 3.53ꢀ3.48 (m, 1H), 2.42ꢀ2.23 (m, 2H), 2.02ꢀ
1.87 (m, 2H); 13C NMR (CDCl3, 100 MHz): δ 62.0, 59.4, 57.9,
50.5, 40.0, 39.1, 29.3, 11.6.
2ꢀHeptylꢀ1,3ꢀdioxolane (6e). 138 mg, yield 80%, pale yellow
1
5
liquid; H NMR (CDCl3, 400 MHz): δ 4.77 (t, J = 4.8 Hz, 1H),
3.93ꢀ3.75 (m, 4H), 1.57 ( (t, J = 4.8 Hz, 2H), 1.35ꢀ1.20 (m, 10H),
0.80 (t, J = 6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz): δ 104.8,
64.9 (2C), 34.0, 31.8, 29.6, 29.3, 24.2, 22.7, 14.2. Anal. calcd for
C10H20O2: C, 69.72; H, 11.7%; Found: C, 69.69; H, 11.69%.
65
4ꢀIodoꢀ2ꢀphenylꢀtetrahydrofuran (7b)
& 2ꢀ(Iodometyl)ꢀ4ꢀ
phenyloxetane (7b′). Inseparable mixture, 219 mg, yield 80%,
1
10
pale yellow liquid; H NMR (CDCl3, 400 MHz): δ 7.42ꢀ7.37 (m,
2ꢀCyclopentylꢀ1,3ꢀdioxolane (6f).35 130 mg, yield 91%, yellow
10H), 5.05ꢀ4.94 (m, 2H), 4.68ꢀ4.61 (m, 1H), 4.43ꢀ4.37 (m, 1H),
gummy mass; 1H NMR (CDCl3, 400 MHz): δ 4.63 (d, J = 5.6 Hz, 70 4.13ꢀ4.09 (m, 1H), 3.89ꢀ3.84 (m, 1H), 3.67ꢀ3.63 (m, 1H), 3.50ꢀ
1H), 3.91ꢀ 3.76 (m, 4H), 2.07ꢀ1.99 (m, 1H), 1.71ꢀ 1.33 (m, 8H);
13C NMR (CDCl3, 100 MHz): δ 107.9. 65.1 (2C), 43.1, 27.7 (2C),
15 25.9 (2C).
3.46 (m, 1H), 2.50ꢀ2.43 (m, 1H), 2.35ꢀ2.28 (m, 1H), 2.06ꢀ1.90
(m, 2H); 13C NMR (CDCl3, 100 MHz): δ 144.0, 129.0, 128.8,
128.6, 128.1, 125.9, 125.8, 74.0, 71.3, 58.2, 50.8, 47.3, 46.4,
30.5, 11.5.
2ꢀCycloheptylꢀ1,3ꢀdioxolane (6g). 138 mg, yield 81%, pale
yellow gummy mass; 1H NMR (CDCl3, 400 MHz): δ 4.60 (d, J =
4.4 Hz, 1H), 3.89ꢀ3.75 (m, 4H), 2.11ꢀ2.07 (m, 1H), 1.67ꢀ1.51 (m,
20 12H); 13C NMR (100 MHz, CDCl3): δ 108.1, 65.1 (2C), 43.2,
28.8 (2C), 26.9 (2C), 26.4 (2C). Anal. calcd for C10H18O2: C,
70.55; H, 10.66%; Found: C, 70.60; H, 10.69%.
75 Acknowledgements
A. Majee is pleased to acknowledge the financial support from
BRNS, Govt. of India (Grant No. 37(2)/14/35/2014ꢀBRNS/563).
A. Hajra acknowledges CSIR, New Delhi, India (Grant No.
02(0168)/13/EMRꢀII) for financial support. We are thankful to
80 DSTꢀFIST and UGCꢀSAP. S. Santra and G. V. Zyryanov
acknowledge the Russian Scientific Fund (Grant # 15ꢀ13ꢀ10033)
for funding.
2ꢀ(1,3ꢀDioxolanꢀ2ꢀyl)ꢀ2ꢀphenylethanol (6h).35 162 mg, yield
1
25 84%, pale yellow gummy mass; H NMR (CDCl3, 400 MHz): δ
7.31ꢀ7.21 (m. 5H), 5.11 (d, J = 5.2 Hz, 1H), 4.08ꢀ4.03( m, 2H),
3.95ꢀ3.75 (m, 4H), 3.10ꢀ3.06 (m, 1H), 2.56 (br, 1H); 13C NMR
(CDCl3, 100 MHz): δ 137.7, 128.5 (2C), 127.2, 106.3, 64.6 (2C),
63.6, 51.4.
Notes and references
aDepartment of Chemistry, VisvaꢀBharati (A Central University),
85 Santiniketan 731235, India
30
Tel./Fax: +913463 261526; Eꢀmail: adinath.majee@visvaꢀbharati.ac.in
bDepartment of Organic Chemistry, Chemical Technological
Institute, Ural Federal University, 19 Mira Str., 620002
Yekaterinburg, Russian Federation
2ꢀBenzylꢀ2ꢀmethylꢀ1,3ꢀdioxolane (6i). 121 mg, yield 68%,
yellow liquid; H NMR (CDCl3, 400 MHz): δ 7.28ꢀ7.22 (m, 5H),
3.92ꢀ3.89 (m, 2H), 3.77ꢀ3.73 (m, 2H), 2.92 (s, 2H), 1.31 (s, 3H);
13C NMR (CDCl3, 100 MHz): δ 137.0, 130.6, 128.1, 126.5,
35 109.9, 64.9, 45.5, 24.4. Anal. calcd for C11H14O2: C, 74.13; H,
7.92%; Found: C, 74.07; H, 7.86%.
1
90 cDepartment of Chemistry, Jhargram Raj College, Midnapore (W),
Jhargramꢀ721507, India
dI. Ya. Postovskiy Institute of Organic Synthesis, Ural Division of the
Russian Academy of Sciences, 22 S. Kovalevskoy Str., 620219
Yekaterinburg, Russian Federation
2ꢀBenzylꢀ2ꢀphenylꢀ1,3ꢀdioxolane (6j). 215 mg, yield 85%,
95
1
yellow liquid; H NMR (CDCl3, 400 MHz): δ 7.31ꢀ7.03 (m, 10
† Electronic Supplementary Information (ESI) available: [NMR spectra
for all compounds]. See DOI: 10.1039/b000000x/
40 H), 3.76ꢀ3.63 (m, 4H), 3.09 (s, 2H); 13C NMR (CDCl3, 100
MHz): δ 142.5, 136.0, 130.9 (2C), 128.0, 127.9, 127.7, 126.4
(2C), 125.9 (2C), 110.0 (2C), 64.8 (2C), 47.1. Anal. calcd for
C17H18O2: C, 79.97; H, 6.71%; Found: C, 79.91; H, 6.73%.
1
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