A method of synthesis of alkyl iodides and bromides

Full text of DOI:10.1134/S1070363208120207

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 12, pp. 2407–2408. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © A.O. Kolodyazhnaya, V.P. Kukhar’, O.I. Kolodyazhnyi, 2008, published in Zhurnal Obshchei Khimii, 2008, Vol. 78, No. 12,
pp. 2061–2062.
LETTERS
TO THE EDITOR
A Method of Synthesis of Alkyl Iodides and Bromides
A. O. Kolodyazhnaya, V. P. Kukhar’, and O. I. Kolodyazhnyi
Institute of Bioorganic and Petroleum Chemistry, National Academy of Sciences of Ukraine,
ul. Murmanskaya 1, Kiev, 02094 Ukraine
e-mail: oikol123@rambler.ru
Received July 3, 2008
DOI: 10.1134/S1070363208120207
Iodine or bromine substitution for OH group in a
C–OH fragment is an ordinary reaction in organic
chemistry [1]. In the case of complex compounds it is
commonly carried out by tosylate method which is
disadvantageous due to low yield of alkyl halide [2].
We found that complex alkyl iodides were conveni-
ently prepared by the treatment of alcohols I with bis(di-
akylamino)chlorophosphine and then by lower alkyl
iodide or bromide. This procedure results in higher
yield of alkyl halides IV and V as compared with the tosy-
late protokol, therewith the reaction is not complicated
by rearrangements, isomerizations and racemization of
the carbon backbone of the initial alcohol. We applied
this procedure to the synthesis of precursors of the C–P
analogs of natural lysophosphatide acid [3] whose
complete synthesis would be published elsewhere.
(
Et N) PCl
EtX
2
2
_
+
ROH
(Et N) POR
[(Et N) P(Et)OR] X
RX
2
2
2
2
Et N
_
3
(Et N) P(O)Et
2 2
_
_
Ia Ic
II
III
IVa, Va Vc
O
O
O
O
X = Br (IV), I (V); R = O
(a);
O
CH2 (b);
(c).
CH2
CH2
CH2
The conversion of alcohols to alkyl halides was
carried out by a one-pot procedure. Initially, alcohol
was treated with bis(diethylamino)chlorophosphine
and then with ethyl iodide or bromide. The reaction of
obtained phosphates with ethyl iodide proceeds
exothermally, with ethyl bromide is completed in a
few hours at room temperature or at light heating. The
reaction resulted in the formation of a mixture of alkyl
halide and ethylphosphonic acid which could be easily
separated by vacuum distillation or column
chromatography. By the data of NMR spectroscopy of
the reaction mixtures the yields of alkyl halides were
quantitative. Pure alkyl halides were isolated in 70–
iodide can be used to achieve greater difference in
boiling points of the reaction products for better
separation. Intermediate compounds II and III were
3
1
registered by P NMR spectroscopy. Phosphonium
salt III was isolated pure from the reaction mixture
obtained at 0°C that allowed its characterization by
1
31
means of H and P NMR spectroscopy. At room
temperature this salt decomposes quantitatively into
alkyl iodide and phosphonate. The purity of the alkyl
1
iodides was confirmed by H NMR spectroscopy,
analytical chromatography, and elemental analysis.
4-Bromomethyl-2,2-dimethyl-1,3-dioxolane (IVa).
To a solution of 0.01 mol of isopropylideneglycerol
and 0.01 mol of triethylamine in 10 ml of anhydrous
diethyl ether at 0°С was added while stirring 0.01 mol
of bis(diethylamino)chlorophosphine in 10 ml of the
8
0% yield due to certain losses at distillation. When
necessary, instead of bis(diethylamino)chlorophos-
phine pairs bis(dimethylamino)chlorophosphine–metyl
iodide or bis(dipropylamino)chlorophosphine–butyl
2407

2
408
KOLODYAZHNAYA et al.
same solvent. Stirring was continued for 30 min, then
the triethylamine hydrochloride was filtered off and
the solvent was evaporated in a vacuum. To the
phosphate was added 0.03 mol of ethyl bromide, and
the mixture was heated at slow boiling for 2 h. Then
volatile products were evaporated at a reduced
pressure and the residue was distilled in a vacum.
Hz): 1.26 s (3H, СН ), 1.31 s (3H, СН ), 1.8 m (2H,
3 3
3
CH CH I), 3.2 т (2H, J 7, CH I), 3.20–3.70 m (1H,
2
2
HH
2
CHO), 3.80–4.10 m (2H, CH O). Found I, %: 49.56.
2
C H IО . Calculated I, %: 49.56 [4].
7
13
2
(R,R)-4,5-Bis(iodomethyl)-2,2-dimethyl-1,3-dioxo-
lane (Vc) was prepared like (Vb). Yield 75%. Color-
less liquid. It was purified by column chromatography
on silica gel, eluent hexane–ethyl acetate, 10:1.
1
Yield 75%, bp 75°C (10 mm Hg). Н NMR spectrum
(
CDСl ), δ, ppm (J, Hz): 1.34 s (3H, CH ), 1.43 s (3H,
1
3
3
Colorless liquid, bp 90°С (0.1 mm Hg). Н NMR
3
4
CH ), 3.30 d.d (1H, J 5.6, J 5.6, CHBr), 3.42 d.d
(
4
3
HH
HH
spectrum (CDСl ), δ, ppm (J, Hz): 1.50 s (6Н, CH ),
3
4
4
3
3
3
1H, J 3, J 3, CHBr), 3.86 d.d (1H, J 5.5, J
HH HH HH HH
3
2
2
.40 m (4H, СН I), 3.89 m (2H, СНО). Found, %: C
3
4
2
.5, CHO), 4.12 d.d (1H, JHH 4.5, J 5.5, CHO),
HH
2.01; H 3.17; I 66.40. C H I O . Calculated, %: C
7
12 2
2
4
.33 m (1H, CHO). Found Br, %: 40.5. C H BrO
6
11
2.
1.91; H 3.18; I 66.10.
Calculated Br, %: 40.96.
The NMR measurements were performed on a
4
-Iodomethyl-2,2-dimethyl-1,3-dioxolane (Va).
1
Varian-300 instrument, references TMS ( Н) and 85%
To a solution of 0.01 mol of isopropylideneglycerol
and 0.01 mol of triethylamine in 10 ml of diethyl ether
at 0°С while stirring was added 0.01 mol of bis
31
Н РО in D O ( Р).
3
4
2
ACKNOWLEDGMENTS
This work was carried out in the framework of the
Program for supporting young scientists of the
National Academy of Sciences of Ukraine.
(
diethylamino)chlorophosphine in 10 ml of the same
solvent. Stirring was continued for 30 min, then the
triethylamine hydrochloride was filtered off and the
solvent was evaporated in a vacuum. To the residue
was added 0.02 mol of ethyl iodide and the mixture
was left standing for 12 h at room temperature. The
pure iodide was isolated by distillation in a vacuum.
REFERENCES
Colorless liquid, yield 80%, bp 85–90°C (10 mm Hg).
1
. Sasson, Y., Formation of Carbon–Halogen Bonds (Cl,
Br, I). The Chemistry of Halides, Pseudo-Halides and
Azides, Patai, S. and Rappoport, Z., Eds., Chichester;
New York: Wiley, part 1, 1995, p. 536.
1
Н NMR spectrum (CDСl ), δ, ppm (J, Hz): 1.34 s
3
3
4
(
5
3H, CH ), 1.43 s (3H, CH ), 3.30 d.d (1H, J 5.6, J
3 3 HH
3
4
.6, CHI), 3.42 d.d (1H, J 3, J 3, CHI), 3.86 d.d
HH HH
4
3
3
(
1H, J 5.5, J 4.5, CHO), 4.12 d.d (1H, J 4.5,
HH HH HH
2. Comprehensive
Organic
Functional
Group
4
JHH 5.5, CHO), 4.33 m (1H, CHO). Found I, %: 52.2.
C H IO . Calculated I, %: 52.43.
Transformations, Katritzky, A.R., Meth-Cohn, O., and
Rees, C.W., Eds., Oxford: Elsevier Science, 1995, vol. 2,
part 1.
6
11
2
(
S)-(–)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dixolane
3. Moolenaar, W.H., J. Biol. Chem., 1995, vol. 270, p. 12949.
(
Vc) was prepared similarly. Yield 75%. Colorless
liquid, bp 100°С (10 mm Hg). n 1.4958, [α] –22.5
c 2.0, CHC1 ). Н NMR spectrum (CDСl ), δ, ppm (J,
2
0
20
D
4. Mori, K. and Watanabe, H., Tetrahedron, 1986, vol. 42,
D
1
p. 295.
(
3
3
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 12 2008