ethyl iodide eros.re092, biotransformation, Dokumenty
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1
ETHYL IODIDE
Ethyl Iodide
1
N
PhMgBr, THF
1. EtI, THF, rt
PPh
3
N
Ph
N
rt
2. NaOH, H
2
O
reflux
N
PPh
3
(
1
)
N
EtI
Ph
NHEt
(2)
[75-03-6]
C
2
H
5
I
(MW 155.97)
Pyrroles were
N
-ethylated (DMSO, KOH, 60% yield) during
the synthesis of novel 2-azafulvenes.
8
In a related reaction, thioethers were prepared in the presence
ofaPt
II
catalyst in 80–90% yield.
9
This reaction was developed as
an alternative to the more traditional method demonstrated by Ono
(DBU/benzene).
10
In a similar fashion, alcohols can be converted
to the corresponding ethyl ethers.
InChI = 1/C2H5I/c1-2-3/h2H2,1H3
InChIKey = HVTICUPFWKNHNG-UHFFFAOYAT
acids;
1
amines,
6
,
8
(esterification
of
carboxylic
alkylation
of
alkoxides, thiolates
9
and enolates;
17
,
21
preparation of Grignard
reagents
22
)
Alternate Name:
iodoethane.
Physical Data:
mp
−
108
◦
C; bp 70–73
◦
C,
d
1.941 g cm
−
3
.
Solubility:
sol water (with decomposition), alcohol, most organic
solvents.
Form Supplied in:
heavy, clear, very refractive liquid; colorless
when pure, becomes red on exposure to light and air due to
iodine liberation; common impurities are ethanol and iodine.
Preparative Methods:
prepared by reaction of ethanol and iodine
in the presence of red phosphorus.
Purification:
purified by shaking with dilute solution of sodium
bisulfite or sodium thiosulfate until colorless; wash with water,
dry (CaCl
2
), and distill. May also be purified by passing through
a column of silica gel or alumina followed by distillation.
Handling, Storage, and Precautions:
store colorless solution over
silver leaf or copper wire in brown bottle away from light. Avoid
storing over mercury as ethylmercury(II) iodide, the byproduct
of decomposition, is extremely poisonous. Harmful if swal-
lowed, inhaled, or absorbed through the skin. Extremely harm-
ful to mucous membranes, upper respiratory tract, eyes, and
skin. Exposure can cause spasms, inflammation of contact area,
coughing, nausea, and vomiting. Use in a fume hood.
C
-Alkylations.
Alkylation of carbon nucleophiles with ethyl
iodide is a convenient method for introducing an ethyl group at a
carbon center. The substrates are treated with base (
t
-BuOK,
11
NaOEt,
12
n
-BuLi,
13
NaHMDS,
14
LiHMDS,
15
LDA,
16
etc.)
followed by quenching with ethyl iodide. The solvent is usually,
but not limited to, THF or diethyl ether. Temperatures and reaction
times vary depending on the specific substrate. Yields also vary
but most appear to be good to excellent (
>
80%). A variety of com-
pounds have been prepared including introduction of quaternary
chiral centers at bridgehead positions (eq 3).
17
O
H
1. LDA, THF, –78 °C
2. EtI, HMPA
H
OTBDMS
O
OTBDMS
Et
H
(3)
OTBDMS
OTBDMS
Esterifications.
Ethyl iodide has seen widespread use as a
reagent for conversion of carboxylic acids to ethyl esters.
1
The
procedure involves treatment of a carboxylic acid with base fol-
lowed by addition of ethyl iodide. The method is particularly use-
ful with substrates containing acid-sensitive protecting groups.
Conditions are varied: HMPA/NaOH (yields
>
95%),
2
DMSO/
KOH (
>
90%),
3
NaHCO
3
/DMF (
>
95%),
4
CsF/DMSO or DMF
(92–100%).
5
The latter method was particularly useful in the di-
rect conversion of organotin carboxylates, commonly employed
to protect carboxylic acids in the presence of amines in pep-
tide synthesis, to esters. The conversion proceeds in excellent
yields (85–91%) at mild temperatures with no racemization
(eq 1).
Asymmetric alkylation reactions have also taken advantage
of the versatility of this reagent. Such chiral enolate systems
as oxazolidinones,
18
dihydropyrimidinones,
19
camphorsulfona-
mides,
20
and chiral lactams
21
have been alkylated in high che-
mical and optical yields. Meyers et al. utilized chiral lactams in a
general preparation of cyclohexenones bearing a tertiary or qua-
ternary chiral center at the C-4 position (eq 4).
21
O
O
HO
HO
LDA, EtI
Red-Al
N
N
LDA, RX
Bu
4
NH
2
PO
4
Et
R
O
O
NHAc
NHAc
O
EtI, CsF, DMF
(1)
R
2
H
R
2
Et
30 °C
(4)
R = Ph,
i
-Pr
REt
Heteroatom Alkylation.
Various heteroatoms react with ethyl
iodide.
N
-Ethylamines, hydrazines,
6
and amides have been pre-
pared. Secondary
N
-ethylamines were prepared by Katritzky et al.
in 55–65% yield via the reaction of (
1
) with ethyl iodide followed
by treatment with NaOH/H
2
O (eq 2).
7
Grignard Reagent.
Conversion of ethyl iodide to its Grig-
nard reagent proceeds easily (Mg, Et
2
O, 0
◦
C). An example of
the utilization of this reagent can be found in the synthesis of a
debromoaplysin analog (eq 5).
22
Avoid Skin Contact with All Reagents
2
ETHYL IODIDE
O
Et
12.
Bishop, J. E.; Nagy, J. O.; O’Connell, J. F.; Rapoport, H.,
J. Am. Chem.
Soc.
1991
,
113
, 8024.
HO
EtMgI, Et
2
O
(5)
13.
Golec, J. M. C.; Hedgecock, C. J. R.; Kennewell, P. D.,
Tetrahedron Lett.
1992
,
33
, 547.
0 °C to rt
93%
O
O
14.
Chu, K. S.; Negrete, G. R.; Konopelski, J. P.; Labner, F. J.; Woo, N.-T.;
Olmstead, M. M.,
J. Am. Chem. Soc.
1992
,
114
, 1800.
15.
Amoroso, R.; Cardillo, G.; Tomasini, C.,
Tetrahedron Lett.
1992
,
33
,
2725.
1.
Haslam, E.,
Tetrahedron
1980
,
36
, 2409.
16.
deJong, J. C.; Feringa, B. L.,
Tetrahedron Lett.
1989
,
30
, 7239.
2.
(a) Shaw, J. E.; Kunerth, D. C.; Sherry, J. J.,
Tetrahedron Lett.
1973
, 689.
(b) Shaw, J. E.; Kunerth, D. C.,
J. Org. Chem.
1974
,
39
, 1968.
17.
Wu, H. Y.; Walker, K. A. M.; Nelson, J. T.,
J. Org. Chem.
1990
,
55
, 5074.
18.
Yan, T. H.; Chu, V. V.; Lin, T. C.; Wu, C. H.; Liu, L. H.,
Tetrahedron
Lett.
1991
,
32
, 4959.
3.
Johnstone, R. A. W.; Rose, M. E.,
Tetrahedron
1979
,
35
, 2169.
4.
Sato, T.; Otura, J.; Nozaki, H.,
J. Org. Chem.
1992
,
57
, 2166.
19.
Negrete, G. R.; Konopelski, J. P.,
Tetrahedron: Asymmetry
1991
,
2
, 105.
5.
Knapp, S.; Gibsen, F. S.,
J. Org. Chem.
1992
,
57
, 4802.
20.
Yen, K. F.; Uang, B. J.,
Tetrahedron: Asymmetry
1992
,
3
, 697.
6.
Barluenga, J.; Merino, I.; Vina, S.; Palacious, F.,
Synthesis
1990
, 398.
21.
(a) Wunsch, T.; Meyers, A. I.,
J. Org. Chem.
1990
,
55
, 4233. (b) Meyers,
A. I.; Berney, D.,
Org. Synth.
1990
,
69
, 55.
7.
Katritzky, A. R.; Jiang, J.; Urozdi, L.,
Synthesis
1990
, 565.
8.
Taheri, S. A. N.; Jones, R. A.; Badesha, S. S.; Harria, M. M.,
Tetrahedron
1989
,
45
, 7717.
22.
Nath, A.; Ghosh, A.; Venkateswaran, R. V.,
J. Org. Chem.
1992
,
57
,
1467.
9.
Page, C. B.; Klair, S. S.; Brown, M. P.; Smith, C. S.; Maginn, J. J.; Mulley,
S.,
Tetrahedron
1992
,
48
, 5933.
Brian A. Roden
Abbott Laboratories, North Chicago, IL, USA
10.
Ono, N.; Miyake, H.; Saito, T.; Kaji, A.,
Synthesis
1980
, 952.
11.
Curran, D. P.; Liu, H.,
J. Am. Chem. Soc.
1992
,
114
, 5863.
A list of General Abbreviations appears on the front Endpapers
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