SODIUM IODIDE 1
R
R
Sodium Iodide1
NaI (excess)
acetone, "
Br
I
(2)
NaI
high yield
H
H
O
O
[7681-82-5] INa (MW 149.89)
NaI (5 equiv)
InChI = 1/HI.Na/h1H;/q;+1/p-1/fI.Na/h1h;/q-1;m
KCN (5 equiv)
O
O
InChIKey = FVAUCKIRQBBSSJ-OJCLKTPSCN NaHCO3 (10 equiv)
(3)
H
H O
O
DMSO, 80 °C
65%
(source of iodide ion for nucleophilic displacement reactions in
CN
OTs
the preparation of alkyl iodides4 10 and aryl iodides11 13 from
halides and sulfonates; in combination with Zn, reduces sulfo- NaI reacts with electron-deficient aryl halides in a formal
nates;14,15 converts vic-dihalides and vic-disulfonates to al- SNAr reaction (e.g. with 2,4-dinitrochlorobenzene)11 to give aryl
kenes;16 20 dehalogenates Ä…-halo ketones21 23 and Ä…-bromo iodides; however, with aryl diazonium compounds the reaction
enones;27 converts acyl chlorides to acyl iodides;24 cleaves aryl proceeds via electron transfer and involves an aryl radical.12
methyl25,26 and some dialkyl ethers;27 32 deoxygenates epo- The latter process has been applied to the Pschorr phenanthrene
xides;31 in combination with TMSCl/MeCN, generates TMSI in synthesis13 (eq 4).13b
situ;33 35 catalyzes phosphorylations;36 reduces ene dicarbonyl
OMe
compounds;37 converts acetylenic ketones to vinyl iodides;38 in
MeO
combination with TMSCl/MeCN/0.5 H2O, generates  anhydrous
HI 40 with various co-reagents, reduces sulfoxides41 43 and N-
1. H2SO4, i-C5H11ONO (2 equiv)
oxides;43a,44,45 with oxidizing agents, iodinates organoboranes,46 2. NaI (4 equiv)
NH2
MeO
phenols,47,48 and aromatic compounds49)
CO2H acetone, 0 °C
ć% ć%
Physical Data: mp 661 C; bp 1304 C; d 3.667 g cm-3.
RO
ć%
Solubility: very sol cold H2O (184 g/100 mL, 25 C), hot H2O
OMe
ć% ć%
(302 g/100 mL, 100 C), alcohol (42.57 g/100 mL, 25 C), ace-
OMe
OMe
ć%
tone (39.9 g/100 mL, 25 C); sol glycerin.2 Also sol acetic acid,
MeO
MeO
acetonitrile, DMF, DMSO, formic acid, HMPA, methyl ethyl
ketone.
Form Supplied in: white solid (crystalline, granular, or powder); + (4)
I
MeO MeO
widely available.
CO2H CO2H
ć%
Drying: can be dried under vacuum at 70 C.3
RO RO
Handling, Storage, and Precautions: deliquescent in moist air
OMe OMe
(gradually absorbs up to ca. 5% (0.5 mol) H2O in air), and
R = CH2Ph 20% 45%
upon long exposure to air will turn brown due to liberation of
R = SO2Ph few % 71%
iodine; storage in a dry or inert atmosphere is recommended.
Reductive Cleavage of Sulfonates. NaI/Zinc has been used to
Introduction. Sodium iodide and potassium iodide are used
reduce alkyl tosylates and mesylates to the corresponding alkanes
in organic synthesis as sources of iodide. NaI is more commonly
(eq 5).14 This procedure complements Lithium Aluminum Hy-
used due to greater solubility in organic solvents and slightly lower
dride reductions of sulfonates since, in some cases, LiAlH4 pro-
cost. Tetraalkylammonium iodides have also been used as organic-
duces both the alkane and the alcohol. However, with secondary
soluble sources of iodide. See also Potassium Iodide and Tetra-
mesylates and tosylates a large amount of the alkene elimination
butylammonium Iodide.
product is often obtained using NaI/Zn. NaI/Zn/D2O (or T2O) in
dimethoxyethane has been used to replace primary and secondary
Displacement Reactions. NaI reacts with alkyl chlorides, bro-
hydroxyl groups with deuterium (or tritium).15
mides, and sulfonates (e.g. mesylates and tosylates4) to provide the
corresponding alkyl iodides.5 The conversion of alkyl halides to
O O
iodides using NaI in acetone is known as the Finkelstein reaction.6
(5)
Though usually an SN2 displacement, radicals have been impli-
cated in some cases.6b Displacement reactions using NaI are
MsO R
numerous in the literature, and representative examples (eqs 1
LiAlH4, ether R = H, 41%; R = OH, 50%
and 2)7,8 are shown below. In some cases the iodo compound is
NaI + Zn, glyme HMPA, 83 °C R = H, 70%
not isolated but reacts with another nucleophile present (eq 3).9
NaI has been used catalytically in such reactions.10
Conversion of vic-Halides and vic-Sulfonates to Alkenes.
NaI (1.6 equiv)
NaI reacts with vic-dibromides, vic-bromochlorides, and vic-di-
MEK
chlorides to give the corresponding alkenes.16 This reaction
87 °C, 24 h
Cl I
(1)
PhCO2 PhCO2
can be utilized for alkene cis/trans isomerization (eq 6).17 vic-
78 81%
Avoid Skin Contact with All Reagents
2 SODIUM IODIDE
O O
Bromochlorides and vic-dichlorides give predominantly cis-
1. NaI , MeCN
I
products while dibromides give predominantly trans-alkenes. rt
Cl O
(9)
vic-Dimesylates17 and vic-ditosylates18,19 also give alkenes when
2. ethylene oxide
0 °C
treated with sodium iodide, via initial displacement of one sul-
70%
Cl Cl
fonate group followed by attack of iodide on the iodine of the
vic-iodosulfonate. This reaction has been carried out under phase-
NaI, NaOAc
acetone
transfer conditions.20 O
O
O 20 °C
O (10)
1. HCl, NBS, CH2Cl2
97%
 78 to  20 °C
O
Pr
(6) OH
(CH2)7OAc Pr (CH2)7OAc
2. NaI (excess)
DMF, 85 °C
93% cis
95%
In Situ Generation of Trimethylsilyl Iodide. NaI/Chlorotri-
methylsilane/MeCN has been widely used as a convenient sub-
Dehalogenation of Ä…-Halo Ketones. NaI will reductively de- stitute for Iodotrimethylsilane.33 35 For example, this reagent
halogenate some Ä…-halo ketones in acidic aqueous THF or dioxane removes benzylic hydroxyl groups,34 cleaves methoxyethoxy-
(eq 7)21 or in AcOH.22 This reaction may not be general for all Ä…- methyl (MEM),35 aryl methyl, and aryl ethyl ethers, deoxygenates
halo ketones.21 NaI/Sulfur Trioxide Pyridine in acetonitrile has sulfoxides (and N-oxides in the presence of zinc), converts some
also been used to carry out this transformation.23 alcohols to iodides, and dehalogenates Ä…-halo ketones.33a
O O
Catalysis of Phosphorylation. NaI catalyzes the phosphory-
NaI (4 equiv)
X
H2O dioxane (1:1)
lation of nucleosides by chlorophosphates, pyrophosphates, and
(7)
triazolides.36 The rate of phosphorylation is greatly enhanced by
"
addition of 1 or 2 equiv of NaI. For example, 3 -O-benzoylthymi-
X = Cl, 55%
dine is phosphorylated over 10 times faster with Diethyl Phospho-
X = Br, 78%
rochloridate when 1 equiv of NaI is added, and over 300 times
faster when 2 equiv of NaI are added.
Preparation of Acyl Iodides. NaI reacts with acyl chlorides in
anhydrous acetonitrile to give acyl iodides in high yield.24 Diacyl
Ä… ²-Unsaturated Carbonyl Compounds.
1,4-Addition to Ä… ²
Ä…,²
diiodides24b and iodoformates24c have also been prepared in this
NaI has been used to reduce the carbon carbon double bond of
fashion.
2-ene-1,4-dicarbonyl compounds, presumably via conjugate ad-
dition of iodide followed by reduction of the newly formed Ä…-
Demethylation of Aryl Methyl Ethers. NaI reacts with aryl
iodo carbonyl compound (eq 11).37 The reaction is specific to
methyl ethers in acetic or formic acid to give the corresponding
1,4-diketones or keto aldehydes, and fails with 1,4-diacids, 1,4-
phenolic derivatives and methyl iodide.25 In one study, KI was
diesters, and Ä…,²-unsaturated monocarbonyl compounds. How-
found to give slightly higher yields (eq 8).26 See also NaI/Me3 ever, NaI apparently does add to enones under some conditions
SiCl/MeCN below.
since NaI/BF3·OEt2 dehalogenates Ä…-bromo enones (via the vic-
bromoiodide).27c Furthermore, NaI in TFA reacts with Ä…,²-ace-
OMe
OMe
NaI (2 equiv)
tylenic ketones to give (E)-²-iodovinyl ketones, while NaI in
O
O
O
O
HCO2H
AcOH gives predominantly the (Z)-isomer (eq 12).38 The reac-
100 °C
(8)
tion tolerates both terminal and substituted alkynes.
90%
O OMe
O OH
C12H25 NaI (2.2 equiv) C12H25
HCl (2.2 equiv)
O O
acetone
rt, 5 min
Other Ether Cleavage Reactions. NaI/Boron Trifluoride
(11)
quantitative
Etherate cleaves some alkyl ethers27 and acetals,27b and converts
OHC OHC
keto epoxides to enones.27c Some primary and secondary alkyl
methyl ethers are cleaved by NaI/Boron Tribromide/15-Crown-
O O I O
5 in CH2Cl2.28 Cyclic (e.g. THF and THP) and acyclic dialkyl
+ (12)
C5H11 C5H11 C5H11 I
ethers are cleaved at the less substituted carbon by NaI in the pres-
ence of acyl chlorides.29 For example, 2-methyltetrahydrofuran
NaI, TFA 30 min  95%
gives the pivalate derivative of 5-iodo-2-pentanol when treated
NaI, AcOH 30 min 70% 17%
with NaI/t-BuCOCl in acetonitrile. Similarly, 2-iodoethyl esters
NaI, AcOH 21 h  94%
are produced from acyl chlorides, Ethylene Oxide, and NaI
(eq 9).30 NaI/Trifluoroacetic Anhydride has been used to deoxy-
genate epoxides with retention of configuration: trifluoroacetyl Conversion of Allylic, Benzylic, and Tertiary Alcohols to
iodide is generated in situ and reacts with the epoxide in the pres- Iodides. NaI/BF3·OEt2 in acetonitrile converts allylic, benzylic,
ence of NaI to give a vic-iodo trifluoroacetate, which decomposes and tertiary alcohols to iodides in good yield.39,40 NaI/Me3SiCl/
in the presence of excess NaI to give the alkene.31 NaI/NaOAc has MeCN/0.5 H2O ( anhydrous HI ) has been used to convert allylic
been reported to reduce Ä…,²-epoxy ketoses to ²-hydroxy ketoses, alcohols to allylic iodides, with allylic rearrangement if the alcohol
presumably via the Ä…-iodo-²-hydroxy ketone (eq 10).32 is secondary or tertiary.40
A list of General Abbreviations appears on the front Endpapers
SODIUM IODIDE 3
Reduction of Sulfoxides. NaI/(CF3CO)2O in acetone,41 NaI/ 14. Fujimoto, Y.; Tatsuno, T., Tetrahedron Lett. 1976, 37, 3325.
BF3·OEt2 in acetonitrile,42 NaI/I2/Hexamethylphosphorous 15. Turecek, F.; Veres, K.; Kocovsky, P.; Pouzar, V.; Fajkos, J., J. Org. Chem.
Triamide in acetonitrile,43a NaI/Oxalyl Chloride in aceto- 1983, 48, 2233.
nitrile,43b NaI/Me3SiCl in acetonitrile,43c NaI/I2/Me2NEt·SO3 in 16. Sonnet, P. E.; Oliver, J. E., J. Org. Chem. 1976, 41, 3284.
acetonitrile,43d and NaI/pyridine·SO3 in acetonitrile43d all reduce 17. Slates, H. L.; Wendler, N. L., J. Am. Chem. Soc. 1956, 78, 3749.
sulfoxides to sulfides in high yield. 18. Foster, A. B.; Overend, W. G., J. Chem. Soc. 1951, 3452.
19. Semmelhack, M. F.; Foos, J. S.; Katz, S., J. Am. Chem. Soc. 1972, 94,
Reduction of N-Oxides and Nitrones. NaI/(CF3CO)2O in 8637.
acetonitrile deoxygenates various heteroaromatic N-oxides and 20. Landini, D.; Quici, S.; Rolla, F., Synthesis 1975, 397.
nitrones in very high yield.44 NaI/pyridine·SO3 deoxygenates di- 21. Gemal, A. L.; Luche, J. L., Tetrahedron Lett. 1980, 21, 3195.
N-oxides of quinoxalines and phenazines.45 NaI/I2/(Me2N)3Pin
22. Bowers, A.; Ringold, H. J., J. Am. Chem. Soc. 1958, 80, 3091.
acetonitrile deoxygenates azoxides.43a
23. Olah, G. A.; Vankar, Y. D.; Fung, A. P., Synthesis 1979, 59.
24. (a) Hoffmann, H. M. R.; Haase, K., Synthesis 1981, 715. (b) Hoffmann,
Iodinations of Phenols and Organoboranes. NaI/Chlora- H. M. R.; Haase, K.; Geschwinder, P. M., Synthesis 1982, 237.
mine-T has been used as an in situ source of Iodine Monochlo- (c) Hoffman, H. M. R.; Iranshahi, L., J. Org. Chem. 1984, 49, 1174.
ride for iodinations of organoboranes46 and phenols.47 For 25. Ulbricht, T. L. V., J. Chem. Soc. 1961, 3345.
example, methyl 5-iodosalicylate is prepared from methyl salicy- 26. Mustafa, A.; Sidky, M. M.; Mahran, M. R., Justus Liebigs Ann. Chem.
1967, 704, 182.
late in 78% yield.47 Iodinated carbohydrates have been prepared
27. (a) Mandal, A. K.; Soni, N. R.; Ratman, K. R., Synthesis 1985, 274.
via iodination of organoboranes (eq 13).46b Recently, NaI/Sodium
(b) Mandal, A. K.; Shrotri, P. Y.; Ghogare, A. D., Synthesis 1986, 221.
Hypochlorite in methanol has been used to iodinate phenols in
(c) Mandal, A. K.; Mahajan, S. W., Tetrahedron 1988, 44,
high yield with good regioselectivity.48 The yield and regioselec-
2293.
tivity with phenol (80% para, 10% ortho, 4%ortho,para) are dif-
28. Niwa, H.; Hida, T.; Yamada, K., Tetrahedron Lett. 1981, 22, 4239.
ferent than those obtained with ICl or NaI/Chloramine-T. Simple
29. Oku, A.; Harada, T.; Kita, K., Tetrahedron Lett. 1982, 23, 681.
aromatic hydrocarbons are iodinated with NaI/O2/cat. Nitroso-
30. Belsner, K.; Hoffmann, H. M. R., Synthesis 1982, 239.
nium Tetrafluoroborate in CH2Cl2/TFA.49 This iodination fails
31. Sonnet, P. E., J. Org. Chem. 1978, 43, 1841.
with electron-deficient aromatics.
32. Paulsen, H.; Eberstein, K.; Koebernick, W., Tetrahedron Lett. 1974,
1. Cy2BH I 4377.
O O
2. NaI (2 equiv)
33. (a) Morita, T.; Okamoto, Y.; Sakurai, H., Yuki Gosei Kagaku Kyokaishi
MsO Chloramine-T MsO
1981, 39, 973. (b) Groutas, W. C.; Felker, D., Synthesis 1980, 861.
O O
NaOAc (2 equiv)
(c) Olah, G. A.; Narang, S. C., Tetrahedron 1982, 38, 2225.
(13)
O O
91%
34. Sakai, T.; Miyata, K.; Tsuboi, S.; Takeda, A.; Utaka, M.; Torii, S., Bull.
Chem. Soc. Jpn. 1989, 62, 3537.
Related Reagents. Sodium Iodide Copper; Trifluoroacetic
35. Rigby, J. H.; Wilson, J. Z., Tetrahedron Lett. 1984, 25, 1429.
Anhydride Sodium Iodide.
36. Strömberg, R.; Stawinski, J., Nucleosides Nucleotides 1987, 6,
815.
37. D Auria, M.; Piancatelli, G.; Scettri, A., Synthesis 1980, 245.
1. (a) Merrell, P. H.; Peters, E. M. In Kirk Othmer Encyclopedia of
38. (a) Taniguchi, M.; Kobayashi, S.; Nakagawa, M.; Hino, T.; Kishi, Y.,
Chemical Technology, 3rd ed.; Wiley: New York, 1983; Vol. 21, p 226. (b)
Tetrahedron Lett. 1986, 27, 4763. (b) TMSI reacts similarly to NaI/TFA:
Anderson, F. N. In Kirk-Othmer Encyclopedia of Chemical Technology,
Cheon, S. H.; Christ, W. J.; Hawkins, L. D.; Jin, H.; Kishi, Y.; Taniguchi,
2nd ed.; Wiley: New York, 1969; Vol. 18, p 485.
M., Tetrahedron Lett. 1986, 27, 4759.
2. CRC Handbook of Chemistry and Physics, 73rd ed.; Lide, D. R., Ed.;
39. Mandal, A. K.; Mahajan, S. W., Tetrahedron Lett. 1985, 26, 3863.
CRC Press: Boca Raton, FL, 1992.
40. Kanai, T.; Irifune, S.; Ishii, Y.; Ogawa, M., Synthesis 1989, 283.
3. Perrin, D. D.; Armarego, W. L. F.; Perrin, D. R., Purification of
41. Drabowicz, J.; Oae, S., Synthesis 1977, 404.
Laboratory Chemicals, 2nd ed.; Pergamon: New York, 1980; p 530.
42. Vankar, Y. D.; Rao, C. T., Tetrahedron Lett. 1985, 26, 2717.
4. Tipson, R. S.; Clapp, M. A.; Cretcher, L. H., J. Org. Chem. 1947, 12,
43. (a) Olah, G. A.; Balaram Gupta, B. G.; Narang, S. C., J. Org. Chem.
133.
1978, 43, 4503. (b) Olah, G. A.; Malhotra, R.; Narang, S. C., Synthesis
5. Chambers, R. D.; James, S. R. In Comprehensive Organic Chemistry;
1979, 58. (c) Olah, G. A.; Narang, S. C.; Balaram Gupta, B. G.; Malhotra,
Barton, D.; Ollis, W. D., Eds.; Pergamon: New York, 1979; Vol. 1, p 513.
R., Synthesis 1979, 61. (d) Olah, G. A.; Vankar, Y. D.; Arvanaghi, M.,
6. (a) Finkelstein, H., Chem. Ber. 1910, 43, 1528. (b) Smith, W. B.; Branum,
Synthesis 1979, 984.
G. D., Tetrahedron Lett. 1981, 22, 2055.
44. Balicki, R., Gazz. Chim. Ital. 1990, 120, 67.
7. Ford-Moore, A. H., Org. Synth., Coll. Vol. 1963, 4, 84.
45. Demirdji, S. H.; Haddadin, M. J.; Issidorides, C. H., J. Heterocycl. Chem.
8. Rosenkranz, G.; Mancera, O.; Gatica, J.; Djerassi, C., J. Am. Chem. Soc.
1983, 20, 1735.
1950, 72, 4077.
46. (a) Kabalka, G. W.; Gooch, E. E., J. Org. Chem. 1981, 46, 2582. (b) Hall,
9. Jung, M. E.; Shaw, T. J., J. Am. Chem. Soc. 1980, 102, 6304.
L. D.; Neeser, J.-R., Can. J. Chem. 1982, 60, 2082.
10. Rorig, K.; Johnston, J. D.; Hamilton, R. W.; Telinski, T. J., Org. Synth.,
47. Kometani, T.; Watt, D. S.; Ji, T., Tetrahedron Lett. 1985, 26, 2043.
Coll. Vol. 1963, 4, 576.
48. Edgar, K. J.; Falling, S. N., J. Org. Chem. 1990, 55, 5287.
11. Bunnett, J. F.; Conner, R. M., Org. Synth., Coll. Vol. 1973, 5, 478.
49. Radner, F., J. Org. Chem. 1988, 53, 3548.
12. Kumar, R.; Singh, P. R., Tetrahedron Lett. 1972, 613.
13. (a) Chauncy, B.; Gellert, E., Angew. Chem., Int. Ed. Engl. 1969, 22, 993.
James J. Kowalczyk
(b) Duclos, R. I., Jr.; Tung, J. S.; Rapoport, H., J. Org. Chem. 1984, 49,
Eisai Research Institute of Boston, Andover, MA, USA
5243.
Avoid Skin Contact with All Reagents