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Chapter ThreeFormation of iodohydrins
Theoretical
Halohydrins are valuable intermediates that can be
transformed into epoxides1, ketones2 and other derivatives3-5.
Chlorohydrins and bromohydrins can be prepared in good yields
`when the halogenation of the alkene is carried out in aqueous
media6.
On the other hand, iodohydrins are frequently prepared from
α-iodoketones, epoxides, other halohydrins and seldom directly
from alkenes because of the reversibility of steps(a) and (b) as
shown in scheme 1.
Survey of literature reveals the formation of halohydrins from various
substrates such as:
(A) Epoxides (B) Carbonyl Compounds (C) Alkenes
which has been described with recent examples.
C C + I2
IC C + I−(a)
(b) H3O++C C
OH
IH2O+
IC C
I2 I−+ I3−
Scheme-1
118
(A) Formation of halohydrins from epoxides.
There is a continued interest in the ring opening of epoxides to the
corresponding vicinal halohydrins7-9. Most of them have some
limitations e.g. in the presence of a suitable catalyst, chlorosilanes
insert selectively into the less substituted C-O bond of 1-alkene
oxides, affording o-silyl chlorohydrins10-12.
In 1959, Parker and Isaacs13 found that methyl-2,3-anhydro-4,6-o-
benzylidene-α-D-alloside (I) gave diequatorial iodohydrin (II) with
methyl magnesium iodide and diaxial-iodohydrin (III) with ethyl
magnesium iodide, while 2,3-anhydro-4,6-o-benzylidene-α-D-
mannoside (IV) gave the same diaxial iodohydrin (V)
diaxial iodohydrin(V)
(IV)
O
OCH3HO
IC6H5HC O
O CH2
orC2H5MgI
CH3MgIO
OCH3
OC6H5HC O
O CH2
(I)
diaxial iodohydrin(III)
Diequatorial iodohydrin(II)
CH3MgI C2H5MgI
C6H5HC O
O CH2
O
OCH3I
OH
O
OCH3I
OHC6H5HC O
O CH2
C6H5HC O
O CH2
O
O
OCH3
119
Hey et al.14 prepared the 3α-Iodo-5α-cholestan-2β-ol (VII) from
2β,3β-epoxy-5α-cholestane (VI) and Iodo-trifluoro-acetate (VIII).
Palumbo et al.15 reported the synthesis of halohydrins (XIV-XXXI)
which can be effected in a one-pot treatment of epoxides (IX-XIII) with
triphenylphosphine and the proper halogen in anhydrous
dichloromethane at room temperature.
O
H
C8H17
HI
CHCl3H
I
HO
(VI) (VII)
(VII)(VIII)
HI
HO
MeOH
aqHCl
H
C8H17
I
CF3COO
O
Ph3P
I2/Br2/Cl2
I
OH
orBr
OH
or
Cl
OH
(IX) (XIV) (XV) (XVI)
120
O I2/Br2/Cl2
Ph3P
OH
I
C
OH
Br
C
or or
OH
Cl
C
(XIX)(XVIII)(XVII)(X)
O
(XX) (XXI) (XXII)
OH
Cl
C
oror
OH
Br
C
OH
I
C
Ph3P
I2/Br2/Cl2
(XI)
O
cholest
(XII)
I2/Br2/Cl2
Ph3P
cholest
I
HO
or
Br
HO
cholest
cholest
Cl
HO
or
(XXIII) (XXIV)
(XXV)
121
Einhorn and Luche16 reported the conversion of various epoxides
(IX, XIII, XXXII-XXXVII) to halohydrins (XIV, XV, XXX, XXXI,
XXXVIII-XLVI) by using tin (II) halides (SnI2/SnCl2/SnBr2) in a
variety of solvents (Et2O/H2O/CH2Cl2/ CCl4).
O
(XIII)
I2/Br2/Cl2
Ph3P
OH
I
+OH
I
or
OH
Br
+OH
Br
or
OH
Cl
+OH
Cl
(XXVI) (XXVII)
(XXVIII) (XXIX)
(XXX) (XXXI)
OSnBr2
Et2O/H2O
Br
OH
CH2Cl2
SnI2
"
I
OH
(IX) (XV)
(XIV)
122
(XLI)
(XL)
ClCH2−CH(OH)−CH2ISnI2
Et2O"
ClCH2−CH(OH)−CH2BrCCl4
SnBr2
(XXXIX)
(XXXVIII)(XXXII)
ClCH2−CH(OH)−CH2ClSnCl2
CH2Cl2
threo−Me−CHCl−CH(OH)MeCCl4
SnCl2
(XXX)
OH
Cl
+OSnCl2
CH2Cl2
Cl
OH
(XIII) (XXXI)
O
Me
Me
ClCH2CH(OH)CH3
(XXXIII)
"
(XLIV)
PhCHICH2OHCH2Cl2
SnI2
"
(XLIII)
PhCHClCH2OHSnCl2
Et2O
O
Ph
(XXXIV)
O
CH CH2Br−CH2
(XXXV)
(XL)(XLII)
BrCH2−CH(OH)−CH2ClCCl4
SnCl2BrCH2CH(OH)CH3
123
Otsubo et al.17 reported that epoxy ester (XLVII-L) can be
converted to α-hydroxyester (LIV-LVII) via the formation of
iodohydrin (LI-LIII) by using MgI2-Bu3SnH.
O
PhOCH2
SnCl2
Et2OPhOCH2CHClCH2OH
(XXXVI) (XLV)
O
threo-Ph COPhCH2Cl2
SnCl2threo−PhCHClCH(OH)COPh
(XXXVII) (XLVI)
O
CO2C8H17OH
I CO2C8H17
OH
CO2C8H17
(XLVII) (LI) (LIV)
OCO2Et
OH
ICO2Et CO2Et
OH
(XLVIII) (LII) (LV)
OCO2Et
ICO2Et
OH
CO2Et
OH
(XLIX) (LIII) (LVI)
124
Joshi et al.18 reported the synthesis of halohydrins (XIV-XVI,
LXIII-LXIX) from meso-epoxides (IX, LIX-LXII) using B-
halodiisopinocampheylboranes (Ipc2Bx) (LVIII).
OCO2Et
(L)
OHCO2Et
Single product
(LVII)
Iodohydrin wasnot detected
x = Cl, Br, IBx2)
(LVIII)
(XIV)
(XV)(IX) (XVI)
or
or
OH
I
OH
Br
OH
Cl
O
IOHO
(LXV)(LX)
(LXIV)(LIX) (LXIII)
or
OH
I
OH
Br
O
125
Sarmah and Barua19 reported that the reaction of AlI3 with less
reactive epoxides (LXX-LXXIII) yielded the corresponding trans
iodohydrin which on further exposure to AlI3 yielded the corresponding
olefins (LXXIV-LXXVII).
O
O
(LXX)
O
(LXXIV)
OAc
O
(LXXI)
OAc
(LXXV)
O
16
(LXXII)
16
(LXXVI)
(LXII) (LXVIII) (LXIX)
or
HO BrHO BrO
(LXVII)(LXVI)(LXI)
or
HO IHO BrO
126
COOMeO6 6
(LXXIII)
66 COOMe
(LXXVII)
Bajwa and Anderson20 reported the use of lithium halides
(LiI/LiBr/LiCl) for opening of epoxides (XXXVI, IX, XXXV,
LXXVIII-LXXXIV) to give halohydrins (XIV, XV, XLIV, LXXXV-
XCVI).
CNO
(LXXVIII)
ICN
OH
(LXXXV)
PO(OCH2Ph)2O
(LXXIX)
IPO(OCH2Ph)2
OH
(LXXXVI)
or
or
ClPhO
OH
(LXXXIX)
(LXXXVIIII)
BrPhO
OHPhO
OIPhO
OH
(XXXVI) (LXXXVII)
OOH
I
OH
Bror
(XIV)(IX) (XV)
127
(LXXX)
PhCH2OO
OCH2Ph PhCH2OOCH2Ph
I
OH
(XC)
TBDMSOO
OSMDBT
(LXXXI) (XCI)
TBDMSOOSMDBT
I
OH
or
MOMOBr
OH
(XCIV)
MOMO
O
(LXXXIII) (XCIII)
MOMOI
OH
THPOOPHT
I
OH
(XCII)(LXXXII)
THPOO
OPHT
AcO
O
(LXXXIV) (XCV)
AcOI
OH
128
Ph
O
PhI
OH
PhOH
I
+
(XXXV) (XCVI) (XLIV)
Chini et al.21 reported the synthesis of β-halohydrins (C-
CXXII, XLIII-XLV, XIV-XVI, LXXXVII-LXXXIX, XXX, XXVI,
XXVIII, XCVI) by the reaction of epoxides (XXXV, IX, XIII,
XCVII-XCIX) with NH4X in acetonitrile in presence of metal salts
and under representative acidic conditions (HX, CHCl3) X=Cl, Br, I.
PhI
OH
PhOH
I
+
(XCVI) (XLIV)
(CII)(CI)
+ PhOH
Br
PhBr
OH
Ph
O
PhCl
OH
PhOH
Cl
+
(XXXV) (C) (XLIII)
"
"
NH4Cl
NH4Br
NH4I
129
(CIV)(LXXXVII)
+Ph
O OH
I
PhO I
OH
PhO Br
OH
PhO OH
Br+
(LXXXVIII) (CIII)
(XLV)(LXXXIX)(XXXVI)
+Ph
O OH
Cl
PhO Cl
OHOO
Ph NH4Cl
NH4Br
NH4I
"
"
OH
I
or
(XIV)
(XV)(IX) (XVI)
or
OH
Br
OH
Cl
O
130
(CX)(CIX)
(CVII) (CVIII)
(CVI)(CV)
+ OH
I
I
OH
Br
OHOH
Br
+
+ OH
Cl
Cl
OH
(XCVII)
ONH4Cl
NH4Br
NH4I
"
"
(CXVI)(CXV)
+C8H17
I
OH
C8H17OH
I
C8H17OH
Br
C8H17Br
OH
+
(CXIII) (CXIV)
(CXII)(CXI)(XCVIII)
+C8H17
Cl
OH
C8H17OH
ClO
C8H17NH4Cl
NH4Br
NH4I
"
"
131
Konaklieva et al.22 reported that iodination of epoxides
(XXXV, XXXVI, LXXX, CXXIII-CXXV) leads to the
formation of iodohydrins (LXXXVII, CXXVI-CXXIX) by
using iodine and acetone.
(XCIX)
CH3OH
Cl
CH3Cl
OH
+
(CXVII) (CXVIII)
(CXX)(CXIX)
+CH3
Br
OH
CH3OH
Br
CH3OH
I
CH3I
OH
+
(CXXI) (CXXII)
O
CH3
NH4Cl
NH4Br
NH4I
"
"
OOH
Cl
OH
Bror
(XXX)(XIII) (XXVIII)
(XXVI)
or
OH
I
132
O
R R' CH3COCH3
I2
I R'
OHR
+O O
R R'
H3C CH3
OO O
I
OH
O O
H3C CH3
O+
(XXXVI) (LXXXVII) (CXXX)
(CXXXI)(CXXVI)(CXXIII)
+O O
H3C CH3
O
NO2
OI
OH
NO2
OO
NO2
O
(CH2)5CH3 (CH2)5CH3I
OHO O
H3C CH3
(CH2)5CH3
+
(CXXIV) (CXXVII) (CXXXII)
O
O O
H3C CH3
(XXXV) (CXXXIII)
133
Naz et al.23 reported that the iodohydrins (CXXXVI-CXXXVIII)
can be prepared by the ring opening of benzyl-2-o-p-tosyl-3,4-anhydro-
β-L-arabinopyranoside (CXXXIV) or benzyl-2,3-anhydro-4-o-acetyl-
α-D-ribopyranoside (CXXXV) respectively using sodium acetate,
sodium iodide and acetic acid in acetone.
O
EtO2CCH2O OCH2CO2Et EtO2CCH2O OCH2CO2Et
IHO
(CXXV) (CXXVIII)
(CXXIX)(LXXX)
PhCH2O OCH2Ph
IHOO
PhCH2O OCH2Ph
OO
OBnOTs
NaOAc
NaI
O
OBnOTs
I
OH
O
OBnOH
AcO
INaI
NaOAcO
OBnO
AcO
O
OBnAcOOH
I+
(CXXXIV) (CXXXVI)
(CXXXVII)(CXXXV) (CXXXVIII)
134
Kotsuki et al.24 describe a simple method for the transformation of
epoxides to β-halohydrins using lithium halides
(LiCl+H2O/LiBr,H2O/LiI) supported on silica gel.
C7H15O
C3H7O
(CLV)(CLIV)(CXL)
Br
OH
C7H15Cl
OH
C7H15
I
OH
C7H15
(CLVI)
(CLIII)
I
OH
C3H7
Cl
OH
C3H7 Br
OH
C3H7
(CXXXIX) (CLI) (CLII)
(XC)(XXXVI)
ClPhO
OHPhO
OIPhO
OH
(LXXXVII)
or
or
or
or
or
135
C13H27O
(CLIX)
I
OH
C13H27
orCl
OH
C13H27 Br
OH
C13H27
(CXLI) (CLVII) (CLVIII)
or
BzOO
(CLXII)
I
OH
BzO
orCl
OH
BzO Br
OH
BzO
(CXLII) (CLX) (CLXI)
or
(XLIII)(C)(XXXV)
+ PhOH
Cl
PhCl
OH
Ph
O
PhBr
OH
PhOH
Br
+
(CI) (CII)
(XLIV)(XCVI)
+ PhOH
I
PhI
OH
"
"
136
(XLI)
I
OH
Cl
Cl
OH
Cl Br
OH
Cl
(CXLIV) (CLXVI) (XL)
ClO
PhI
OH
PhOH
I
+
(XCVI) (CLXV)
(CLXIV)(CI)
+ PhOH
Br
PhBr
OH
Ph
O
PhCl
OH
PhOH
Cl
+
(CXLIII) (C) (CLXIII)
"
"
or
or
(CLXIX)
(CLXVIII)(CLXVII)(CXLV)
O
O
I
I
OH
OH
O
O
Br
Br
OH
OH
O
O
Cl
Cl
OH
OH
O
OO
O
or
or
137
Kotsuki et al.24 also observed that α,β-epoxy ketones
(CXLVIII-CL) produced α-haloenone derivatives (CLXXVI-
CLXXXIV). The results can be explained by the mechanism
depicted in scheme II.
OOH
Cl
OH
Br
(XVI)(IX) (XV)
(XIV)
OH
I
or
or
(CLXXIII)
O
O
OH
I
O
O
OH
Br
(CLXXII)(CLXXI)
O
O
OH
Cl(CXLVII)
O
OO
(CLXX)
OH
I
(CXLVI)
O
138
Scheme-II
X
O
X−
B:
O
HO+ X
O
H
HHO+
O
O
SiO O Si O Si O
Silica gelLiXO
O
(CLXXIV)
(CLXXV)
I
O
(CLXXVIII)
(CLXXVII)
Br
O
O
O
Cl
O
(CLXXVI)(CXLVIII)
or
or
I
O
(CLXXXI)
(CLXXX)
Br
O
O
O
Cl
O
(CLXXIX)(CXLIX)
or
or
139
Sharghi et al.25 reported the synthesis of halohydrins from
epoxide using macrocycle diamides as well as crown ethers in
presence of elemental halogen.
O
O
(CL)
O
Cl
O
Br
O
I
(CLXXXII) (CLXXXIII)
(CLXXXIV)
(XV)(IX) (XIV)
OH
Br
OH
I
O
(CXXIV)
n-Hex
O
n-HexBr
OH
(CLXXXVIII)(CXXVII)
n-HexI
OH
(CLXXXVI)(CLXXXV)
IiPrO
OHiPrO
OBriPrO
OH
(CLXXXVII)
(LXXXVIII)
BrPhO
OHPhO
OIPhO
OH
(XXXVI) (LXXXVII)
PhI
OH
(XCVI) (CI)
PhBr
OH
Ph
O
(XXXV)
or
or
or
or
or
140
Sharghi and Eskandari25 carried out the conversion of epoxides
into halohydrins with elemental halogen catalyzed by thiourea under
various reaction conditions.
+Ph
OH
Br
(CII)(CI)
PhBr
OH(Me2N)2BBr
CH2Cl2,N2"
"n-Bu4NBr,Mg(NO3)2
CHCl3Ph
Br
OH
(CI) (CII)
PhOH
Br
+
+Ph
OH
I
(XLIV)(XCVI)
PhI
OHLiI, AcOH,THF
"
O O
H3C CH3
Ph
(CXXXIII)
"I2,acetone
(CII)
PhOH
BrHI/HBr,CHCl3
PhOH
I
(XLIV)
"
"
(CII)
PhOH
BrBr2,CH2Cl2
Br2/I2,CH3CNPh
I
OH
(XCVI) (CI)
PhBr
OH
Ph
O
(XXXV)
or
or
141
I2, acetone
(CXCIV)
IH13C6
OH
"+ O O
H3C CH3
H13C6
(CXCV)
(CXCIII)
BrH13C6
OH
H13C6O
IH13C6
OH
(CLXXXIX) (CXCII)
I2/Br2,CH3CN
+
OH4-Br-C6H4O
Br
(CXCI)
Br2,CH2Cl2
(CXC)
Br4-Br-C6H4O
OH
"
(CXXX)
O O
H3C CH3
PhO
+" IPhO
OH
(LXXXVII)
I2, acetone
I2/Br2,CH3CN
(LXXXVII)(XXXVI)
IPhO
OH
PhOO
BrPhO
OH
(LXXXVIII)
or
or
142
or
or
or
(XV)(IX) (XIV)
OH
Br
OH
I
O I2/Br2,CH3CN
Br2,CH2Cl2OH
Br
(XV)
"
"
(XV)
OH
Br
LiBr,AcOH,THF
I
OH
Br Br
OH
Br
(XXXIV) (CXCVI) (CXCVII)
BrO I2/Br2,CH3CN
I2/Br2,CH3CNCl
O
(XL)(XLI)(CXLIV)
Br
OH
ClI
OH
Cl
143
Soroka and Goldeman27 reinvestigated the reaction performed by
Sharghi and Eskandari26 by using stoichiometric amount of thiourea in
presence of excess of water.
(CCII)(CCI)
nHX
(CC)
OHR
X
+XR
OH
OR
where X = I/Br
Sulfur + side products + nHXwaterX2
H2N S
NH2+X−
S NH2
NH2+X−
X2H2N NH2
S
(CXCVIII) (CXCIX)
144
(B) Formation of halohydrins from carbonyl compounds.
Imamoto et al.28 reported the formation of iodohydrins by
iodomethylation of simple, α,β-unsaturated and diketones using
diiodomethane and samarium diiodide.
n−C6H13COCH3 n−C6H13C(OH)(CH2I)CH3
(CCIII) (CCXIX)
OOH
CH2I
(CCIV) (CCXX)
O OH
CH2I
(CCV) (CCXXI)
C6H5COCH3 C6H5C(OH)(CH2I)CH3
(CCXXII)(CCVI)
COCH3
(CCVII) (CCXXIII)
C(OH)(CH2I)CH3
145
O
(CCVIII) (CCXXIV)
OH
CH2I
CHO
n−C11H23CHO n−C11H23CHOHCH2I
(CCXXV)(CCIX)
CHOHCH2I
(CCX) (CCXXVI)
C6H5CHO C6H5CHOHCH2I
(CCXXVII)(CCXI)
(CCXXIX)(CCXIII)
(CH3)2C=CH(CH2)2C(CH3)=CHCHOHCH2I(CH3)2C=CH(CH2)2C(CH3)=CHCHO
(CCXXX)(CCXIV)
OH
CH2IO
146
Tabuchi et al.29 reported similar conversions with the same
reagents almost at the same time.
n−C6H13CO(CH2)2COC6H13−n n−C6H13C(OH)(CH2I)(CH2)2C(OH)(CH2I)C6H13−n
(CCXV) (CCXXXI)
CH3CO(CH2)3COCH3 CH3C(OH)(CH2I)(CH2)3C(OH)(CH2I)CH3
(CCXXXII)(CCXVI)
C6H5CO(CH2)3COC6H5 C6H5C(OH)(CH2I)(CH2)3C(OH)(CH2I)C6H5
(CCXVII) (CCXXXIII)
(CCXVIII)
C6H5CO(CH2)4COC6H5
(CCXXXIV)
C6H5C(OH)(CH2I)(CH2)4C(OH)(CH2I)C6H5
PhCHO
Ph
OH
CH2I
(CCXXXV) (CCXLIV)
(CCXLV)(CCXXXVI)
Ph
OH
CH2IPh
O
O
(CCXXXVII) (CCXLVI)
HO CH2I
147
OOH
CH2I
(CCXLVII)(CCXXXVIII)
OOH
CH2I
(CCIV) (CCXX)
OOH
CH2I
(CCXLVIII)(CCXXXIX)
O
MeO
CH2IHO
(CCXL) (CCXLIX)
OEt
O
OO
OHCH2IO
(CCXLI) (CCL)
O CH2I
OH
OH
CH2I+
(CCXLII)(CCLI)
(CCLII)
148
It is interesting to note that when dibromomethane is used in place
of diiodomethane only iodomethylation occurred and no case of
bromohydrin is obtained.
Ph CHO
(CCXLIII)
PhCH2I
OH
PhCH2I
OH
+
(CCLIII) (CCLIV)
Ph
O
Ph
OH
CH2I
(CCXXXVI) (CCXLV)
(CCXX)(CCIV)
OH
CH2IO
(CCLII)
(CCLI)(CCXLII)
+OH
CH2I
CH2I
OH
O
149
Tabuchi29 also converted the iodohydrin to corresponding epoxide
by using alkali which on further treatment with SmI3 regenerated the
original iodohydrin.
Ph
O
(CCXLVa)(CCXLV)
Ph
OH
CH2I
NaOH/MeOH−H2O
SmI3/THF
R
R'O
CH2X2
2SmI2 R' CH2X
OSmI2R
R'
OR SmI2X
R' CH2I
OHR
(CCLV) (CCLVI)
150
(C) Formation of halohydrins from alkenes.
A simplified procedure for preparing iodohydrins (CCLIX,
CCLX) from alkene (CCLVII, CCLVIII) has been developed by
Sumrell et al.30 utilizing olefin diiodide, aqueous acetone and hydrogen
peroxide.
CH3CH2CH2CH=CH2 CH3CH2CH2CHICH2I CH3CH2CH2CH−CH2IOH
(CCLVII) (CCLIX)
CH3CH=CH2 CH3CHICH2I CH3CHCH2I
OH
(CCLVIII) (CCLX)
Cornforth and Green6 found that HOI generated from I2 and H2O also
add to double bonds, if the reaction is carried out in presence of an
oxidizing agent such as HIO3
2I2 + HIO3 + 5C3H6 + 2H2O 5C3H6(OH)I
(CCLXI) (CCLXII)
151
An alternative oxidizing system was also taken, when iodine in aqueous
dioxane containing a little sodium nitrite was stirred, mixture of propene
(CCLXI) and oxygen gas was absorbed and propene iodohydrin
(CCLXII) was isolated.
2I2 + O2 + 4C3H6 + 2H2O 4C3H6(OH)I
(CCLXII)(CCLXI)
Antonioletti et al.31 reported the formation of iodohydrins by
oxidation of olefin-iodine complexes with pyridinium dichromate.
(CCLXIII)
C5H11 IOHC5H11
(CCLXX)
(CCLXIV)
C10H21
(CCLXXI)
IOHC10H21
Ph
(CCLXV) (CCLXXII)
IOHPh
152
(CCLXVI)
C9H19
t-Bu
IOHC9H19
t-Bu
(CCLXXIII)
Ph
t-Bu
(CCLXVII) (CCLXXIV)
IOHPh
t-Bu
OAc
(CCLXVIII)
OAc
I
OH
(CCLXXV)
(CCLXIX)
OAc
(CCLXXVI)
OAc
I
OH
153
Acton et al.32 reported that functionalization of ring A of
compound (CCLXXVII) was achieved by treatment with
CF3COOAg/I2. The compound (CCLXXVII) regio and
stereospecifically yielded corresponding iodohydrin (CCLXXVIII).
O
O
OH
OH HCH2R
O
O
OH
OH HCH2R
I
OH
O
CH
Me
HO NHTFA
where R =
(CCLXXVII) (CCLXXVIII)
Masuda et al.33 reported a new synthetic method of
preparing iodohydrins from various alkenes through in situ
generation of hypohalous acids from H5IO6 in the presence of
NaHSO3
(CCLXXIX)
I
OH
(CCXCI)
(CCLXXX)
I
OH
(CCXCII)
154
(CCLXXXI) I
OH
(CCXCIII)
(CCLXXXII)
OH
I
+(CCXCIV)
I
OH
(CCXCV)
(CCLXXXIII)
I
OH
(CCXCVI)
(CCLXXXIV)
OH
OH
OH
I(CCXCVII)
(CCLXXXIV)
OH
OH
I
OH
(CCXCVIII)
155
OH
(CCLXXXV)
OH
OH
I
(CCXCIX)
(CCLXXXVI)
OH OH
OH
I
(CCXCVIII)
(CCLXXXVII)
OH
(CCC)
OH
I
OH
(CCLXXXVIII)
O OOH
I
(CCCI)
O
(CCLXXXIX) (CCCII)
OHO
I
(CCXC)OH
I
(CCCIII)
156
Mattos and Sanseverino34 reported the synthesis of iodohydrins
from various alkenes using diverse metal salts.
(CCLXXXIII)(CCXCVI)
I
OH
(CCCIV)
IHO
(CCCVIII)
(CCCV)
(CCCIX)
I
OH
(CCCVI)
OH
I
(XCVI)
(CCCVII) (CCCX)
IOH
158
Asensio et al.35 reported the synthesis of iodohydrins
from olefins by electrophilic addition of hypoiodous acid
(IOH) generated by oxidation of iodomethane (IMe) with
dimethyldioxirane (DMDO).
(CCLXXXIII)(CCXCVI)
I
OH
(CCCXI)
CH3
(CCCXXII)
ICH3OH
(CCCXII)
C2H5C5H11
C5H11C2H5
I
OH
(CCCXXIII)
(CCCXIII) (CCCXXIV)
I
OH
OH
I
+
(CCCXXV)
ICH3 + DMDOCH3COCH3
−70oC[IOH]
olefin
−40oC or r.t.HO
R1
R4
I
R3
R2
158
(CCCXIV)
I
OH
(CCCXXVI)
C6H5
(CCCVI)
(XCVI)
C6H5I
OH
(CCCVII)
C6H5
CH3
C6H5I
OH
CH3
(CCCX)
p−CH3−O−C6H4
(CCCXV)p−CH3−O−C6H4
I
OH
(CCCXXVII)
(CCCXVI)
p−Cl−C6H4
p−Cl−C6H4I
OH
(CCCXXVIII)
(CCCXVII)
p−CH3−C6H4
(CCCXXIX)
p−CH3−C6H4I
OH
159
(CCCXVIII)
p−CF3−C6H4
p−CF3−C6H4I
OH
(CCCXXX)
(CCCXIX)(CCCXXXI)
I
OH
CH3H3C
H3C CH3 CH3
I
HO
H3C
CH3H3C
O
CH3CH3H3C
H3C
(CCCXX) (CCCXXXII)
(CCCXXXIII)(CCCXXI)
C6H5
I
HO
HH5C6
HHH
H5C6 C6H5
H5C6
H
H5C6
O
H
Costantino et al.36 reported that glycals (CCCXXXIV-
CCCXXXVI) can be converted to corresponding 2-deoxy
sugars (CCCXXXVIII) using N-iodosuccinimide and obtained
2-deoxy-2-iodo sugar (CCCXXXVII-CCXXXIX and CCCXL)
as an intermediate.
160
R = TIPS/trityl
(CCCXL)
O
I
OBnOBn
BnO
OH
OOROBn
BnO
(CCCXXXVI)
R = Bn/TIPS
OOR
OHBnO
BnO
I
(CCCXXXIX)
OOR
BnO
BnO
(CCCXXXV)
Na2S2O4H2O,DMF, r.t.
(CCCXXXVIII)
OOBnOBn
BnO
OH
(CCCXXXVII)(CCCXXXIV)
O
I
OBnOBn
BnO
OH
OOBnOBn
BnO
161
Smietana et al.37 reported that iodohydrins can be prepared in one
step procedure by treating the corresponding alkenes at –20oC with
N-iodosuccinimide in a mixture of H2O and DME.
(CCLXXXIII)
I
OH
(XIV)
(CCCVI)
C6H5
C6H5I
OH
(XCVI)
OH
(CCCXLI)
OH
I
OH
(CCCL)
(CCCXLII)
O
(CCCLI)
O
I
OH
O
(CCCXLIII)
(CCCLII)
O
I
OH
(CCLXXXVIII)
O
(CCCI)
OOH
I
162
O
(CCCXLIV)
O
IOH
(CCCLIII)
O
(CCCXLV) (CCCLIV)
O
IOH
OEt
O
(CCCXLVI) (CCCLV)
OEt
OOH
I
(CCCXLVII)
OEt
O
OEt
O
IOH
(CCCLVI)
(CCCXLVIII)
OH
O
OH
OOH
I(CCCLVII)
OH
O
(CCCXLIX)
8
(CCCLVIII)
OH
O
HO
I
8
163
Corso et al.38 isolated the iodohydrins from alkenes studied
earlier also using a mixture of molecular iodine and phenyliodine
(III) bis(trifluoroacetate) (BTI), in CH3CN-H2O as solvent at –15oC.
(CCCVI)
Ph
PhI
OH
(XCVI)
(CCCXIV)(CCCXXVI)
I
OH
(CCLXXIX) (CCXCI)
I
OH
(CCCLIX)
I
OH
(CCCLXVI)
(CCLXXXIII)
I
OH
(CCXCVI)
(CCCLX)
I
OH
(CCCLXVII)
164
(CCCLXI)
OCOCH3
IHO
OCOCH3
(CCCLXVIII)
(CCCXLIII)
O O
I
OH
(CCCLII)
OH
O
(CCCLXII) (CCCLXIX)
OH
O
I
OH
(CCLXXXVIII)
O
O OH
I
(CCCI)
(CCCXLII)
OO
I
OH
(CCCLI)
(CCCLXIII)
O
OBn
BnO
BnO
O
OBn
BnO
BnO I
OH
(CCCLXX)
165
O
OAc
AcO
AcO
(CCCLXIV) (CCCLXXI)
O
OAc
AcO
AcO I
OH
(CCCLXV)
OAcO
AcO
(CCCLXXII)
OAcO
AcO I
OH
Chen et al.39 reported the synthesis of iodohydrins from alkenes
using polystyrene-supported phenyliodine(III)bis (trifluoroacetate)
(CCLXXXIII) (CCXCVI)
I
OH
(CCCXIV)
I
OH
(CCCXXVI)
I(OOCCF3)2R1
R2
+ I2+CH3CN,H2O
R1 I
R2HO
r.t.
+
I
166
(CCCVII)
IOH
(CCCX)
Ph
(CCCVI)
(XCVI)
PhI
OH
(CCLXXIX)
I
OH
(CCXCI)
OC2H5
O
(CCCXLVI) (CCCLV)
OC2H5
O
I
OH
Villegas et al.40 reported the preparation of iodohydrins by the
reaction of alkenes with iodine and water at room temperature in
presence of acid commercial clays (K-10 and KSF) and natural Brazilian
clays (F-101 and F-117).
(CCLXXXIII) (CCXCVI)
I
OH
Ph
(CCCVI)
(XCVI)
PhI
OH
167
(CCCVII)
IOH
(CCCX)
(CCLXXIX)
I
OH
(CCXCI)
Urankar et al.41 reported the synthesis of halohydrins from
deactivated alkenes by the use of N-Bromo and N-Iodosaccharin.
YPh
NBSaC
or NISaC
YPh
OR
Br
YPh
OR
I
or
Ph Me
O
or Ph
OH
I
Me
O
Ph
OH
Br
Me
O
(CCCLVI) (CCCLXII) (CCCLXIII)
(CCCLXV)(CCCLXIV)(CCCLVII)
Ph
OH
Br
Ph
O
Ph
OH
I
Ph
O
orPh Ph
O
168
(CCCLXIX)(CCCLXVIII)(CCCLIX)
Ph
OH
Br
OMe
O
Ph
OH
I
OMe
O
orPh OMe
O
or CNPh
OH
I
CNPh
OH
Br
CNPh
(CCCLX) (CCCLXX) (CCCLXXI)
(CCCLXI) (CCCLXXIII)
O
Br
OH
O
(CCCLXXII)(CCLXXXIX)
OHO
Br
O
169
Discussion
Iodohydrins are interesting synthetic intermediates whose
preparation has been the subject of several recent reports.
However the direct synthesis of iodohydrins from olefins is
usually difficult to achieve.
We have made an attempt to synthesize iodohydrins from
some easily accessible steroidal olefins such as 3β-
hydroxycholest-5-ene (CCCLXXIV), 3β-acetoxycholest-5-ene
(CCCLXXV), cholest-5-ene (CCCLXXVI). 3β-acetoxystigmast-5-
ene (CCCLXXVII) and stigmasterol (CCCLXXVIII) using
aqueous 1,4-dioxane and diverse metal salts.
C10H19
HO
(CCCLXXVIII)
(CCCLXXVII)R = OH (CCCLXXIV)
= OAc (CCCLXXV)= H (CCCLXXVI)
C10H21
AcO
C8H17
R
170
These reactions were carried out at room temperature by
stirring together 2-3 mol. equivalent of steroidal olefins, 31.5
mol. equivalent of iodine and 40 mol. equivalent of the metal
salt, led to iodohydrins as the unique organic product along with
the metal iodide which is generally produced almost
quantitatively as an insoluble solid. No significant amount of
diol, epoxide or diiodide compound was detected in the crude
product. Iodohydrins obtained are characterized by comparison of
its spectral data (IR, 1HNMR and C13NMR).
It is observed that the ease of formation of iodohydrins
varies with the metal ion change and the anion change as shown
in Table-I. The study clearly shows that the formation of
iodohydrins takes place in presence of transition metal ions.
Cu(OAc)2 was observed to be most efficient giving highest yield,
while Fe2(SO4)3 is in close contest with it. The proposed
methodology is simple, the reagents employed are cheap and
easily available and further more, there is no need of special
techniques.
The results of the reaction of steroidal olefins and iodine in
aqueous 1,4-dioxane in the presence of diverse metal salts and a
counter ion of low nucleophilicity are summarized in Table-I.
The detailed discussion and characterization of compounds
is illustrated with I2-H2O-Cu(OAc)2-1,4-dioxane combination as
the suitable representative example.
171
Table-I
Formation of iodohydrins by the reaction of steroidal alkene with iodine in aqueous 1,4-dioxane
Metal salts
3-hydroxycholest
-5-ene (CCCLXXIV)
3-acetoxycholest
-5-ene (CCCLXXV)
Cholest-5-ene(CCCLXXVI)
3-acetoxystigmast
-5-ene (CCCLXXVII)
Stigmasterol(CCCLXXVIII)
Reaction
time (hr)
%yield
Reaction
time (hr)
%yield
Reaction
time (hr)
%yield
Reaction
time (hr)
%yield
Reaction
time (hr)
%yield
Cu(OAc)2
2 65 1 91 1 75 4 90 4 68
NaOAc
2 31 2 38 2 35 4 42 5 32
Pb(OAc)2
3 30 3 40 3 40 5 35 4 30
CuSO4
2 40 1 30 1 35 5 38 6 38
CdSO4
2 36 1 42 2 45 5 45 4 35
ZnSO4
2 30 1 32 2 38 6 37 5 20
FeSO4
120
10 120
20 120
15 120
22 120
10
Fe2(SO4)3
2 60 1 90 1 70 4 89 4 65
AgNO3
5 22 6 28 8 20 6 30 5 25
172
Reaction of 3-hydroxycholest-5-ene (CCCLXXIV) with iodine in
aqueous dioxane in presence of Cu(OAc)2.
To a stirred solution of steroidal substrate (CCCLXXIV) and
Cu(OAc)2 in 1,4-dioxane and water, I2 in small portions is added at
room temperature. After completion of reaction, it was worked up and
chromatographed over silica gel column which furnished pure
compound (CCCLXXIX) having m.p. = 109oC.
(CCCLXXIX)
C8H17
HO
(CCCLXXIV)
HOHO
I
HOHO
I
(CCCLXXIXa)
HOHO
I
(CCCLXXIXb)
(CCCLXXIXc)
HOHO
I
173
Characterization of the compound M.P. = 109oC as 3,5-dihydroxy-
6-iodo-5-cholestane (CCCLXXIX).
The elemental analysis of the compound corresponded to
the molecular composition of C27H47O2I (positive Beilstein test)
which indicated the incorporation of (OH+I) during the course of
reaction, suggesting that iodohydrin is formed. The band at 3401
and 3603 cm -1 in IR spectrum suggested the presence of two
hydroxy groups, other band at 530 cm -1 is ascribable to C-I.
Therefore, the molecular composition and IR spectral values
suggested the presence of iodohydrin in the compound and hence
four isomeric structures (CCCLXXIX), (CCCLXXIXa),
(CCCLXXIXb) and (CCCLXXIXc) could be formulated.
A clear distinction between these four isomers is
possible with the help of its NMR spectrum. The 1H NMR
spectrum of the compound displayed a multiplet centered at
δ 3.9 (W ½ =16 Hz, axial) can be ascribed to C3-αH which
suggested that ring junction A/B is trans. Since A/B ring
junction is trans so the structure (CCCLXXIXa) and
(CCCLXXIXc) could be discarded wherein A/B ring junction
is cis and C3-αH (equatorial) would have given a peak with
J value less than 10 cps. A doublet of a doublet at δ 2.7 (W
½ = 12 Hz, axial) can be taken as on carbon having iodine,
this suggested that the compound is 6-iodo. The W ½ for C6-
H clearly shows that it is axial, β-oriented thus rendering
the iodine as α-equatorially oriented. This discarded the
structure (CCCLXXIXb). Other NMR values can be easily
explained on the basis of structure (CCCLXXIX) as given.
Two singlets for two hydroxy protons appear at δ2.9 and δ
174
3.1. Methyl protons appeared at δ 1.15 (C10-CH3), δ 0.70
(C13-CH3), 0.95 and 0.81 (other methyl protons). C1 3NMR
spectrum of compound showed peaks at δ 77.33 for C5 and δ
32.40 for C6 carbons. Thus on the basis of above discussion
compound m.p. = 109oC may be best characterized as 3β ,5-
dihydroxy-6α-iodo-5α-cholestane (CCCLXXIX).
Reaction of 3-acetoxycholest-5-ene (CCCLXXV) with iodine in
aqueous dioxane in presence of Cu(OAc)2.
To a well stirred solution of steroidal substrate (CCCLXXV) and
Cu(OAc)2 in 1,4-dioxane and water, iodine in small portions was added
at room temperature. After completion of reaction, the mixture was
worked up and chromatographed over silica gel to get a pure compound
having m.p. = 202-204oC (CCCLXXX).
(CCCLXXX)
C8H17
AcO
(CCCLXXV)
AcOHO
I
AcOHO
I
(CCCLXXXa) (CCCLXXXb)
AcOHO
I
AcOHO
I
(CCCLXXXc)
175
Characterization of the compound, M.P. = 202-204oC as 3-
acetoxy-5-hydroxy-6-iodo-5-cholestane (CCCLXXX).
The compound with m.p. = 202-204oC was analyzed for
C29H49O3I (positive Beilstein test). IR spectrum of the compound
exhibited absorption bands at 1709 (CH3COO), 3412 (C-OH), 1048
(C-O) and 520 cm-1 (C-I). This shows that iodohydrin is formed and
the acetoxy group is intact. 1H NMR spectrum displayed a multiplet
centered at δ 5.2 for one proton can be ascribed to C3-αH (W ½ = 15
Hz). A doublet of a doublet centered at δ 2.16 for one proton can be
ascribed to C6-βH (W ½ = 13 Hz) which suggested the ring junction
A/B is trans. A sharp singlet for the methyl protons of acetoxy
moiety was appeared at δ 2.02 and singlet for hydroxy proton
appeared at δ 3.54. These NMR values are compatible with the NMR
spectrum of the earlier compound (CCCLXXIX) discussed and
hence with the same reasoning structure (CCCLXXX) is preferred
over the other possible structures (CCCLXXXa), (CCCLXXXb) and
(CCCLXXXc). C13NMR spectrum showed peaks at δ 76.69 for C5, δ
32.12 for C6, δ71.30 for C3 carbons and δ 170.96 for (COO). On the
basis of foregoing discussion the compound with m.p. = 202-204oC
may be regarded as 3β-acetoxy-5-hydroxy-6α-iodo-5α-cholestane
(CCCLXXX).
Reaction of cholest-5-ene (CCCLXXVI) with iodine in aqueous
dioxane in presence of Cu(OAc)2.
To a solution of steroidal substrate (CCCLXXVI) and Cu(OAc)2
in 1,4-dioxane and water, I2 in small portions was added with stirring
at room temperature. After completion of reaction, it was worked up
176
and chromatographed over silica gel column to furnished pure
compound (CCCLXXXI) having m.p. = 140oC.
Characterization of the compound, M.P. = 140oC as
5-hydroxy-6-iodo-5-cholestane (CCCLXXXI).
The compound showed molecular composition C27H47OI
(positive Beilstein test). From the molecular composition, it is
evident that iodine and hydroxy group were added to the parent
compound and the bands at 3516 cm-1 and 547 cm-1 in its IR
spectrum suggested the presence of hydroxy group and carbon
iodine bond respectively. In the 1H NMR spectrum of the
compound a band at δ 2.75 C6-βH (W ½ = 13 Hz, axial), δ 3.4 for
hydroxy proton was observed. In the absence of substituent at C3
it is difficult to say that ring junction A/B is trans and 5OH is α-
axially oriented. But because in the earlier two cases this ring
junction is proved to be trans, the same is anticipated for this
compound also. C13NMR spectrum showed peaks at δ 79.11 for C5
and δ 35.73 for C6 carbons. From these observations, the
compound having m.p. = 140oC was characterized as 5-hydroxy-
6α-iodo-5α-cholestane (CCCLXXXI).
(CCCLXXVI)
C8H17 C8H17
HOI
(CCCLXXXI)
177
Reaction of 3-acetoxystigmast-5-ene (CCCLXXVII) with
iodine in aqueous dioxane in presence of Cu(OAc)2.
To a well s t irred solution steroidal substrate
(CCCLXXVII) and Cu(OAc) 2 in 1,4-dioxane and water,
iodine in small port ions was added at room temperature.
After completion of reaction, the reaction mixture was
worked up and chromatographed over si l ica gel column.
A compound (CCCLXXXII) melting at 135 oC was
obtained.
Characterization of the compound, M.P. = 135oC as 3-
acetoxy-5-hydroxy-6-iodo-5-stigmastane (CCCLXXXII) .
The elemental analysis of the compound m.p. = 135oC
corresponded to the molecular composition of C31H53O3I
(positive Beilstein test) which indicated the incorporation of
(CCCLXXXII)
C10H21
AcO
(CCCLXXVII)
HOI
AcO
HOI
AcO
(CCCLXXXIIa) (CCCLXXXIIb)
HOI
AcO HOI
AcO
(CCCLXXXIIc)
178
(OH+I) during the course of reaction, suggesting that
iodohydrin is formed. The IR spectrum exhibited band at
1732 (OCOCH3), 3442 (C-OH), 1035 (CO) and 530 cm -1 (C-
I). Therefore, the molecular composition and IR spectral
values suggested the presence of iodohydrin and the acetoxy
group is intact in the compound and hence four isomeric
structures (CCCLXXXII), (CCCLXXXIIa), (CCCLXXXIIb)
and (CCCLXXXIIc) could be formulated.
A clear distinction between these four isomers is
possible with the help of the its NMR spectrum. The 1H NMR
spectrum of the compound displayed a multiplet centered at δ
4.95 for one proton (W ½ = 14 Hz) can be ascribed to C3-αH
which suggested that ring junction A/B is trans. Since A/B
ring junction is trans so the structure (CCCLXXXIIa) and
(CCCLXXXIIc) could be discarded wherein A/B ring junction
is cis and C3-αH (equatorial) would have given a peak with J
value less than 10 cps. A triplet for one proton at δ 2.19 can
be taken as on carbon having iodine, this suggested that the
compound is 6-iodo. The W ½ = 5.4 Hz for C6-H clearly
shows that it is equatorial, α-oriented, thus rendering the
iodine as β-axially oriented. This discarded the structure
(CCCLXXXIIb). Other NMR values can be easily explained
on the basis of structure (CCCLXXXII) as given. A sharp
singlet for three proton appeared at δ 2.0 for methyl protons
of acetoxy group. A peak at δ 3.1 can be ascribed for hydroxy
proton. C13NMR shows peak at δ 71.40 for C5, δ 33.66 for
C6, and δ 170.20 for (COO) carbons. Therefore, on the basis
179
of these evidences the compound m.p. = 135oC can best be
characterized as 3β-acetoxy-5-hydroxy-6β-iodo-5α-
stigmastane (CCCLXXXII).
Reaction of stigmasterol (CCCLXXVIII) with iodine in
aqueous dioxane in presence of Cu(OAc)2.
To a solution of steroidal substrate (CCCLXXVIII) and
Cu(OAc)2 in 1,4-dioxane and water, iodine in small portions
was added with stirring at room temperature. After work up
and column chromatography over silica gel a compound was
obtained having m.p. = 145oC (CCCLXXXIII).
(CCCLXXVIII)
C10H19
HO
(CCCLXXXIII)
HOI
HO
HOI
HO
(CCCLXXXIIIa) (CCCLXXXIIIb)
HOI
HOHO
I
HO
(CCCLXXXIIIc)
180
Characterization of the compound M.P. = 145oC as 3,5-
dihydroxy-6-iodo-5-stigmast-22-ene (CCCLXXXIII).
Elemental analysis of the compound showed the molecular
composition C29H49O2I (positive Beilstein test). The IR spectrum
of the compound exhibited bands at 3439 and 3673 for 2(OH), 532
cm-1 (C-I). The 1H NMR showed a multiplet centered at δ 4.1
integrating for one proton can be ascribed to C3-αH (W ½ = 16
Hz) and a triplet at δ 2.9 can be ascribed to C6-αH (W ½ = 4.4
Hz) for one proton. Two broad singlets appear at δ 4.9 and δ 5.9
for two hydroxy proton. These NMR values are compatible with
the NMR spectrum of the earlier compound (CCCLXXXII)
discussed and hence with the same reasoning structure
(CCCLXXXIII) is preferred over the other possible structures
(CCCLXXXIIIa), (CCCLXXXIIIb) and (CCCLXXXIIIc).
C13NMR showed peaks at C5=68.75, C6=32.40, C22=129.32 and
C23=138.22 indicating the presence of double bond at C22. On the
basis of foregoing discussion, the compound can best be
characterized as 3β,5-dihydroxy-6β-iodo-5α-stigmast-22-ene
(CCCLXXXIII).
181
Experimental
Reaction of 3-hydroxycholest-5-ene (CCCLXXIV) with iodine in
aqueous dioxane in presence of Cu(OAc)2: 3,5-dihydroxy-6-iodo-
5-cholestane (CCCLXXIX).
To a stirred solution of 3β-hydroxycholest-5-ene
(CCCLXXIV) (1 gm; 2.5 mmol) and Cu(OAc)2 (8 gm; 40 mmol)
in 1,4-dioxane (20 ml) and water (20 ml), I2 (8 gm; 31.5 mmol)
was added in small portion at room temperature. After 2 hr,
insoluble Cu2I2 was filtered off, CHCl3 (20 ml) was added and
the organic layer was washed with a saturated solution of
Na2S2O3 (3×5 ml) and brine (5 ml). After drying over anhydrous
sodium sulphate, the organic solvent was filtered off and
evaporated under reduced pressure. The crude product obtained
was chromatographed over silica gel. Each fraction of 25 ml was
taken. Elution with light petroleum (60-80oC)/ether (90:10) gave
the unreacted 3β-hydroxycholest-5-ene (CCCLXXIV) (0.01 gm).
Further elution with light petroleum/ether (80:20) gave a solid
which was recrystallized from methanol to give 3β,5-dihydroxy-
6α-iodo-5α-cholestane (CCCLXXIX) having m.p. = 109 oC, yield
= 0.65 gm.
Molecular formula =C27H47O2I
Molecualr weight =529
IR (vma x) =3401 and 3603 cm-1 (2OH group),
530 cm-1 (C-I)
1H NMR (CDCl3) =3.9 (m, 1H, C3-αH, W ½ = 16 Hz,
axial), 2.7 (dd, 1H, C6-βH, W ½ =
12 Hz, axial), 2.9 and 3.1 (2s,2-
OH proton), 1.15 (C10-CH3), 0.70
=
=
=
=
182
(C13-CH3), 0.95 and 0.81 (other
methyl protons)
C13 NMR (CDCl3) =C1=27.98, C2=29.88, C3=62.98
C4=42.33, C5=77.33, C6=32.40
C7=35.74, C8=35.70, C9=51.33
C10=42.20, C11=20.63, C12=39.95
C13=42.56, C14=56.22, C15=24.17
C16=28.13, C17=56.84, C18=12.15
C19=11.75, C20=29.68, C21=18.63
C22=39.48, C23=23.82, C24=39.84
C25=28.80, C26=22.79, C27=22.53
Reaction of 3-acetoxycholest-5-ene (CCCLXXV) with iodine
in aqueous dioxane in presence of Cu(OAc) 2: 3-acetoxy-5-
hydroxy-6-iodo-5-cholestane (CCCLXXX) .
To a well stirred solution of 3β-acetoxycholest-5-ene
(CCCLXXV) (1g; 2.3 mmol) [Prepared as described in chapter
one] and Cu(OAc)2 (8gm; 40 mmol) in 1,4-dioxane (20 ml) and
water (20 ml), I2 (8 gm; 31.5 mmol) was added in small portion
at room temperature. After 1 hr, insoluble Cu2I2 was filtered off,
CHCl3 (20 ml) was added and the organic layer was washed with
a saturated solution of Na2S2O3 (3×5ml) and brine (5 ml). After
drying over anhydrous sodium sulphate, the organic solvent was
filtered off and evaporated under reduced pressure. The crude
product obtained, was chromatographed over silica gel. Each
fraction of 25 ml was taken. Elution with light petroleum (60-
=
183
80oC)/ether (95:5) gave the unreacted 3β-acetoxycholest-5-ene
(0.02 gm). Furtehr elution with light petroleum/ether (90:10)
gave a solid which was recrystallized from methanol to give 3β-
acetoxy-5-hydroxy-6α-iodo-5α-cholestane (CCCLXXX) having
m.p. = 202-204oC, yield = 0.91 gm.
Molecular formula =C29H49O3I
=Molecualr weight =572
IR (vma x) =1709 cm -1 (CH3COO), 3412 cm -1
(C-OH), 1048 cm -1 (C-O) and 520
cm -1 (C-I)
1H NMR (CDCl3) =5.2 (m, 1H, C3-αH, W ½ 15 Hz,
axial), 2.16 (dd, 1H, C6-βH, W = ½
13 Hz, axial), 2.02 (s, 3H,
CH3COO), 3.54 (s, proton of
hydroxy group), 1.2 (C10-CH3), 0.69
(C13-CH3), 0.97 and 0.81 (other
methyl protons).
C13 NMR (CDCl3) =C1=26.67, C2=27.98, C3=71.30
C4=36.91 C5=76.69, C6=32.12
C7=34.57, C8=35.82, C9=45.37
C10=42.73, C11=21.44, C12=39.48
C13=39.90, C14=55.82, C15=23.92
C16=28.69, C17=56.29, C18=16.68
C19=12.13, C20=29.19, C21=18.65
C22=36.16, C23=24.13, C24=38.28
C25=28.21, C26=22.79, C27=22.54
C1'=170.96, C2'=21.07
=
=
=
=
184
Reaction of cholest-5-ene (CCCLXXVI) with iodine in aqueous
dioxane in presence of Cu(OAc)2: 5-hydroxy-6-iodo-5-
cholestane (CCCLXXXI) .
To a stirred solution of cholest -5-ene (CCCLXXVI) (1g;
2.7 mmol) [Prepared as described in chapter one] and Cu(OAc) 2
(8gm; 40 mmol) in 1,4-dioxane (20 ml) and water (20 ml), I2 (8
gm; 31.5 mmol) was added in small portion at room temperature.
After 1 hr, insoluble Cu2I2 was filtered off, CHCl3 (20 ml) was
added and the organic layer was washed with a saturated solution
of Na2S2O3 (3×5ml) and brine (5 ml). After drying over
anhydrous sodium sulphate, the organic solvent was filtered off
and evaporated under reduced pressure. The crude product
obtained, was chromatographed over silica gel. Each fraction of
25 ml was taken. Elution with light petroleum (60-80oC) gave the
unreacted cholest-5-ene (0.03 gm). Further elution with light
petroleum/ether (90:10) gave a solid which was recrystallized
from methanol to give 5-hydroxy-6α-iodo-5α-cholestane
(CCCLXXXI) having m.p. = 140oC, yield = 0.75 gm.
Molecular formula =C27H47OI
Molecualr weight =514
IR (vma x) =3516 cm -1 (C-OH), 547 cm -1 (C-I)
1H NMR (CDCl3) =2.75 (dd, 1H, C6-βH, W = ½ 13 Hz,
axial), 3.4 (s, proton of hydroxy
group), 1.10 (C10-CH3), 0.68 (C13-
CH3), 0.91 and 0.80 (other methyl
protons).
C13 NMR (CDCl3) =C1=30.52, C2=22.81, C3=19.93
=
=
=
=
=
185
C4=42.24, C5=79.11, C6=35.73
C7=37.39, C8=36.09, C9=44.99
C10=42.97, C11=20.37, C12=34.63
C13=43.07, C14=56.11, C15=23.84
C16=26.82, C17=56.45, C18=13.86
C19=12.00, C20=28.06, C21=18.62
C22=39.46, C23=23.89, C24=39.63
C25=27.99, C26=22.55, C27=21.01
3-acetoxystigmast-5-ene (CCCLXXVII).
A mixture of β-sitosterol (100 gm), pyridine (150 ml) and
freshly distilled acetic anhydride (100 ml) was heated on a water
bath for 2 hr. A brown solution was obtained which after cooling
was poured onto crushed ice water mixture with stirring. The
white precipitate thus obtained was filtered under suction,
washed with water and air-dried. The crude acetate was
recrystallized from acetone, yield = 90 gm, m.p. = 120oC
(reported m.p. = 120oC)42 .
Reaction of 3-acetoxystigmast-5-ene (CCCLXXVII) with
iodine in aqueous dioxane in presence of Cu(OAc) 2: 3-
acetoxy-5-hydroxy-6-iodo-5-stigmastane (CCCLXXXII) .
To a well stirred solution of 3β-acetoxystigmast-5-ene
(CCCLXXVII) (1g; 2.2 mmol) and Cu(OAc)2 (8gm; 40 mmol) in
1,4-dioxane (20 ml) and water (20 ml), I2 (8 gm; 31.5 mmol) was
added in small portion at room temperature. After 4 hr, insoluble
Cu2I2 was filtered off, CHCl3 (20 ml) was added and the organic
186
layer was washed with a saturated solution of Na 2S2O3 (3×5ml)
and brine (5 ml). After drying over anhydrous sodium sulphate,
the organic solvent was filtered off and evaporated under reduced
pressure. The crude product obtained, was chromatographed over
silica gel. Each fraction of 25 ml was taken. Elution with light
petroleum (60-80oC)/ether (95:5) gave the unreacted 3β-
acetoxystigmast-5-ene (0.02 gm). Further elution with light
petroleum/ether (90:10) gave a solid which was recrystallized
from methanol to give 3β-acetoxy-5-hydroxy-6β-iodo-5α-
stigmastane (CCCLXXXII) having m.p. = 135oC, yield = 0.90
gm.
Molecular formula =C31H53O3I
Molecualr weight =600
IR (vma x) =1732 cm -1 (CH3COO), 3442 cm -1
(C-OH), 1035 cm -1 (C-O) and 530
cm -1 (C-I)
1H NMR (CDCl3) =4.95 (m, 1H, C3-αH, W ½ = 14 Hz,
axial), 2.19 (t, 1H, C6-αH, W = ½
5.4 Hz, equatorial), 2.0 (s, 3H,
CH3COO), 3.1 (s, proton of hydroxy
group), 1.15 (C10-CH3), 0.65 (C13-
CH3), 0.95 and 0.82 (other methyl
protons).
C13 NMR (CDCl3) =C1=27.22, C2=28.08, C3=65.16
C4=38.82, C5=71.40, C6=33.66
C7=34.99, C8=35.87, C9=45.83
C10=42.32, C11=21.33, C12=39.77
=
=
=
=
=
187
C13=42.44, C14=56.17, C15=24.05
C16=29.15, C17=56.78, C18=15.36
C19=11.85, C20=26.11, C21=18.70
C22=36.13, C23=23.05, C24=50.97
C25=28.76, C26=20.58, C27=20.19
C28=21.92, C29=11.96, C1'=170.20
C2'=17.58
Reaction of stigmasterol (CCCLXXVIII) with iodine in
aqueous dioxane in presence of Cu(OAc)2: 3 ,5-dihydroxy-6-
iodo-5-stigmast-22-ene (CCCLXXXIII).
To a stirred solution of stigmasterol (CCCLXXVIII) (1 gm;
2.4 mmol) and Cu(OAc)2 (8 gm; 40 mmol) in 1,4-dioxane (20 ml)
and water (20 ml), I2 (8 gm; 31.5 mmol) was added in small
portion at room temperature. After 4 hr, insoluble Cu 2I2 was
filtered off, CHCl3 (20 ml) was added and the organic layer was
washed with a saturated solution of Na2S2O3 (3×5 ml) and brine
(5 ml). After drying over anhydrous sodium sulphate, the organic
solvent was filtered off and evaporated under reduced pressure.
The crude product obtained was chromatographed over silica gel.
Each fraction of 25 ml was taken. Elution with light petroleum
(60-80oC)/ether (90:10) gave the unreacted stigmasterol
(CCCLXXVIII) (0.02 gm). Further elution with light petroleum/
ether (80:20) gave a solid which was recrystallized from
methanol to give 3β,5-dihydroxy-6β-iodo-5α-stigmast-22-ene
(CCCLXXXIII) having m.p. = 145oC, yield = 0.68 gm.
188
Molecular formula
=
C29H49O2I
Molecualr weight =556
IR (vma x) =3439 and 3673 cm -1 (2OH group),
532 cm -1 (C-I)
1H NMR (CDCl3) =4.1 (m, 1H, C3-αH, W ½ = 16 Hz,
axial), 2.9 (t, 1H, C6-αH, W ½ = 4.4
Hz, equatorial), 4.9 and 5.1 (brs,
protons of hydroxy group), 1.14
(C10-CH3), 0.71 (C13-CH3), 0.96
and 0.81 (other methyl protons)
C13 NMR (CDCl3) =C1=29.89, C2=31.87, C3=65.66
C4=40.47, C5=68.75, C6=32.40
C7=34.87, C8=39.30, C9=55.62
C10=42.22, C11=24.12, C12=39.87
C13=42.59, C14=56.95, C15=25.40
C16=28.81, C17=59.28, C18=15.93
C19=12.05, C20=29.71, C21=18.97
C22=129.32,C23=138.22, C24=51.21
C25=31.10, C26=21.16, C27=20.63
C28,=25.39, C29=12.24
=
=
=
=
=
189
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193
