HYDROGEN IODIDE 1
Aqueous HI has been used with a phase-transfer catalyst to
Hydrogen Iodide1
hydriodinate alkenes (eq 2).8 Similarly, it has been used to convert
dialkylalkynes to the corresponding (Z)-vinyl iodides (eq 4).9
HI
Et2PhN · BI3
AcOH
I (3)
[10034-85-2] HI (MW 127.91)
82%
InChI = 1/HI/h1H
InChIKey = XMBWDFGMSWQBCA-UHFFFAOYAO
57% HI
I
80 °C, 4 h
Pr Pr Pr (4)
(electrophilic hydriodination of alkenes and alkynes;3 10 cleav-
92%
Pr
age of epoxides,1b,11,12 ethers, and acetals;13 conversion of
alcohols to iodides;14 17 reducing agent for many groups includ-
ing quinones,24,25 Ä…-diketones,23 Ä…-ketols,23 Ä…-halo ketones,19 A particularly convenient method for generating HI in situ in-
volves the use of various inorganic and organic iodides in the pres-
Ä…-diazo ketones,22 and sulfoxides;30 reductive cyclization of keto
ence of appropriately prepared silica gel or alumina (eq 2).10 These
acids27,28)
adsorbents also facilitate the addition process. Surface-mediated
Alternate Name: hydriodic acid.
hydriodination of phenylalkynes affords the (E) isomers, result-
ć%
Physical Data: 57% aqueous solution: bp 127 C; d 1.70 g cm-3.
ing from syn addition (eq 5).10 The regiochemical course of these
Solubility: sol most common organic solvents.
hydroiodinations follows Markovnikov s rule.
Form Supplied in: compressed gas; colorless 57% aq solution;
PI3, CH2Cl2, Al2O3
widely available.
I
25 °C, 0.3 3 h
Preparative Methods: from the reaction of tetrahydronaphtha-
Ph R Ph (5)
76 85%
lene with I2;2 can be generated in situ (a) from Me3SiCl and NaI
R = Me, Ph or t-Bu
R
in the presence of water,3 (b) from I2 and activated alumina,4
(c) from KI and H3PO4,5 and (d) from Et2PhN·BI3 and AcOH.6
Purification: distillation of the aqueous azeotrope; concentrated
Cleavage of Epoxides to Iodohydrins. The addition of HI
solutions can be regenerated after long storage by treatment
to epoxides to give iodohydrins proceeds readily using either
with hypophosphorous acid.
aqueous HI or anhydrous HI in organic solvents.1b,11 Because
Handling, Storage, and Precautions: store protected from air and
of the difficulty of preparing anhydrous HI, aqueous solutions
light at or below rt. Highly corrosive and toxic. This reagent
have most often been used for this transformation. The stereo-
should be handled in a fume hood.
and regioselectivity of the addition process is similar to the gen-
eral trends discussed for the corresponding additions with HCl (see
Hydrogen Chloride). Trimethylsilyl-substituted epoxides give the
Hydriodination of Alkenes and Alkynes. Being a stronger corresponding iodohydrins with particularly high stereo- and re-
acid, HI undergoes addition more readily than Hydrogen Chloride giospecificity (eq 6).12
or Hydrogen Bromide to most alkenes and alkynes.1a Moreover,
57% HI, Et2O
OHex OH
there is no competing radical addition as with HBr. However,
0 °C
TMS TMS (6)
because of the difficulty in generating and transferring anhydrous
Hex 100%
Hex I Hex
HI, addition of HI has received less attention than addition of
HCl and HBr. As mentioned above, several techniques have been
developed for generating HI in situ. These include the use of KI and
Cleavage of Ethers and Acetals. HI readily cleaves ethers
H3PO4 (eq 1);5 Me3SiCl and NaI in the presence of water (eq 2);3
to alcohols and/or iodides13 and is an attractive reagent for this
I2 and activated Al2O3 (eq 2);4 and the Et2PhN·BI3 complex and
transformation from the standpoint of economy and convenience.
AcOH (eq 3).6 Alternatively, I(py)2BF4 has been used with the
Primary and secondary alkyl methyl ethers are cleaved to afford
hydride donor Et3SiH (eq 1).7
alcohols (or derivatives), while benzyl and tertiary alkyl ethers
often yield iodides. Acetals react in a similar fashion to produce
I
ketones, although this deprotection method rarely offers advan-
(1) tages over more common procedures.
KI, H3PO4, 80 °C, 3 h 88 90%
Conversion of Alcohols and Chlorides to Iodides. The re-
I(py)2BF4, HBF4, Et3SiH, 20 °C, 1 h 50%
action of 57% aqueous HI with saturated primary and secondary
alcohols at elevated temperatures leads in fair to high yield to the
corresponding iodides.14 Tertiary iodides have been synthesized
C5H11 in good to high yields from the corresponding alcohols under es-
(2)
C5H11
I pecially mild conditions by 55% aqueous HI in the presence of
Lithium Iodide.15 Allylic alcohols are transformed to allylic io-
98%
TMSCl, NaI, H2O, 25 °C, 1 h
dides by HI generated in situ from Me3SiCl/NaI.16 Benzylic alco-
83%
I2, Al2O3, 36 °C, 2 h
97%
57% HI, C16H33(Bu)3PBr, 115 °C, 0.25 h
hols are subject to conversion to the saturated system, presumably
98%
TMSI, SiO2, 25 °C, 1 h
via iodine substitution and ensuing reduction (eq 7).17
Avoid Skin Contact with All Reagents
2 HYDROGEN IODIDE
OH
O
48% HI
", 6 h
HI
(7)
(11)
OH 73%
AcOH
O
Alkyl iodides can also be synthesized via treatment of sec-
O
OH
ondary and tertiary alkyl chlorides with anhydrous HI in the pres-
MeI HI
ence of catalytic amounts of FeI3.18
AcOH
Reduction ofÄ…-Substituted Ketones. Treatment of various
OH
O
Ä…-substituted ketones with HI leads to reductive scission of the
Ä…-substituent. Reductive dehalogenation of Ä…-halo ketones can
thus be accomplished with HI to furnish the corresponding ketones (12)
in high yield (eq 8).19 Reaction occurs readily even with sterically
hindered substrates. Related procedures employing cat. NaI or
57% aq HI and phosphorous acid in acetonitrile20 or NaI in concd
H2SO421 require long reaction times, high temperatures, and/or
A method for the construction of fused polyarenes entails re-
reactive substrates and are less satisfactory.
action of a smaller aromatic ring system with phthalic anhydride
followed by reductive cyclization of the keto acid product with
HI in acetic acid to form a polyarene with two additional rings
O
O
HI
(eq 13).27,28 This method conveniently combines three steps (re-
(8)
duction of the carbonyl group, cyclodehydration, and reduction)
Br
into one step.
57% HI
HO2C O
Ä…-Diazo ketones are reduced to methyl ketones by 47% aqueous red phosphorus
(13)
HI in CHCl3 (eq 9).22 The reaction with HI differs from that of HBr
AcOH
and HCl, which give halomethyl ketones as products. Presumably,
", 24 h
80%
the initially formed iodomethyl ketone is reduced to the saturated
ketone under the reaction conditions.
Reductive Deoxygenation of Aryl Ketones. The com-
O
O
bination HI/P/HOAc effectively deoxygenates aryl ketones
N2 47% HI
(eq 14).27 29 While this method is utilized infrequently, it rep-
(9)
CHCl3
resents a useful alternative to the better known Wolff Kishner
97%
and Clemmensen reduction methods.
O
HI
R CO2H (14)
Ä…-Diketones and Ä…-ketols are reduced to the corresponding sat-
R CO2H
AcOH
urated ketones in good yields by aqueous HI in acetic acid at reflux
(eq 10).23
Reduction of Sulfoxides to Sulfides. Sulfoxides are readily
deoxygenated by HI without the complicating halogenation that
Et
OH 47% HI
often accompanies reduction using HBr or HCl.30
AcOH
Et (10)
Et
", 2 h
Et
O
O 80%
Reduction of Alkenylsilanes. Hydriodic acid reacts with
vinylsilanes with replacement of R3Si by hydrogen (eq 15).31 A
small amount of I2 and water (or D2O) is also effective. These
reactions usually occur with retention of configuration.
Reduction of Quinones and Phenols to Arenes. Polycyclic
Hex Hex Hex
57% HI
quinones may be reduced to polyarenes by HI in HOAc at re-
(15)
+
flux (eq 11).24,25 In resistant cases, concentrated aqueous HI may
PhH
TMS
0.25 h
be employed; addition of phosphorus often results in cleaner re-
85% 6%
action by removing the I2 formed. Large excess of HI or pro-
longed reaction time may lead to overreduction. Since hydro-
quinones and phenols are intermediates in these reactions, they
are also readily reducible with this reagent. Reductive methyla- 1. (a) Larock, R. C.; LeLong, W. W., Comprehensive Organic Synthesis
1991, 4, 269. (b) Parker, R. E.; Isaacs, N. S., Chem. Rev. 1959, 59, 737.
tion of quinones can be accomplished in high yield by reaction
2. Hoffman, C. J., Inorg. Synth. 1963, 7, 180.
of polycyclic quinones with excess Methyllithium followed by
reduction with HI (eq 12).26 3. Irifune, S.; Kibayashi, T.; Ishii, Y.; Ogawa, M., Synthesis 1988, 366.
A list of General Abbreviations appears on the front Endpapers
HYDROGEN IODIDE 3
4. Pagni, R. M.; Kabalka, G. W.; Boothe, R.; Gaetano, K.; Stewart, L. J.; 15. Masada, H.; Murotani, Y., Bull. Chem. Soc. Jpn. 1980, 53, 1181.
Conaway, R.; Dial, C.; Gray, D.; Larson, S.; Luidhardt, T., J. Org. Chem.
16. (a) Kanai, T.; Irifune, S.; Ishii, Y.; Ogawa, M., Synthesis 1989, 283.
1988, 53, 4477.
(b) Kanai, T.; Kanagawa, Y.; Ishii, Y., J. Org. Chem. 1990, 55, 3274.
5. (a) Stone, H.; Shechter, H., Org. Synth., Coll. Vol. 1963, 4, 543.
17. Parham, W. E.; Sayed, Y. A., Synthesis 1976, 116.
(b) Kropp, P. J.; Adkins, R., J. Am. Chem. Soc. 1991, 113, 2709.
18. Yoon, K. B.; Kochi, J. K., J. Org. Chem. 1989, 54, 3028.
6. Reddy, C. K.; Periasamy, M., Tetrahedron Lett. 1990, 31, 1919.
19. Penso, M.; Mottadelli, S.; Albanese, D., Synth. Commun. 1993, 23, 1385.
7. Barluenga, J.; Gonzalez, J. M.; Campos, P. J.; Asensio, G., Angew. Chem.,
20. Mandal, A. K.; Nijasure, A. M., Synlett 1990, 554.
Int. Ed. Engl. 1985, 24, 319.
21. Gemal, A. L.; Luche, J. L., Tetrahedron Lett. 1980, 21, 3195.
8. Landini, D.; Rolla, F., J. Org. Chem. 1980, 45, 3527.
22. (a) Wolfrom, M. L.; Brown, R. L., J. Am. Chem. Soc. 1943, 65, 1516.
9. Hudrlik, P. F.; Kulkarni, A. K.; Jain, S.; Hudrlik, A. M., Tetrahedron
(b) Pojer, P. M.; Ritchie, E.; Taylor, W. C., Aust. J. Chem. 1968, 21, 1375.
1983, 39, 877.
23. (a) Reusch, W.; LaMahieu, R., J. Am. Chem. Soc. 1964, 86, 3068.
10. (a) Kropp, P. J.; Daus, K. A.; Crawford, S. D.; Tubergen, M. W.; Kepler,
(b) Hoeger, C. A.; Johnston, A. D.; Okamura, W. H., J. Am. Chem. Soc.
K. D.; Craig, S. L.; Wilson, V. P., J. Am. Chem. Soc. 1990, 112, 7433.
1987, 109, 4690.
(b) Kropp, P. J.; Daus, K. A.; Tubergen, M. W.; Kepler, K. D.; Wilson,
24. Konieczny, M.; Harvey, R. G., J. Org. Chem. 1979, 44, 4813.
V. P.; Craig, S. L.; Baillargeon, M. M.; Breton, G. W., J. Am. Chem. Soc.
25. Konieczny, M.; Harvey, R. G., Org. Synth., Coll. Vol. 1990, 7, 18.
1993, 115, 3071. (c) Kropp, P. J., Crawford, S. D., J. Org. Chem., 1994,
59, 3102. 26. Konieczny, M.; Harvey, R. G., J. Org. Chem. 1980, 45, 1308.
11. (a) Buchanan, J. G.; Sable, H. Z. In Selective Organic Transformations; 27. Platt, K. L.; Oesch, F., J. Org. Chem. 1981, 46, 2601.
Thyagarajan, B. S., Ed.; Wiley: New York, 1972; Vol. 2, p 1. (b)
28. Harvey, R. G.; Leyba, C.; Konieczny, M.; Fu, P. P.; Sukumaran, K. B., J.
Armarego, W. L. F. In Stereochemistry of Heterocyclic Compounds;
Org. Chem. 1978, 43, 3423.
Taylor, E. C.; Weissberger, A., Eds.; Wiley: New York, 1977; Vol. 2, p
29. Ansell, L. L.; Rangarajan, T.; Burgess, W. M.; Eisenbraun, E. J.; Keen,
23. (c) Bártok, M.; Láng, K. L. In The Chemistry of Functional Groups.
G. W.; Hamming, M. C., Org. Prep. Proced. Int. 1976, 8, 133.
Supplement E: The Chemistry of Ethers, Crown Ethers, Hydroxyl Groups
30. (a) Madesclaire, M., Tetrahedron 1988, 44, 6537. (b) Ookuni, I.; Fry, A.,
and Their Sulfur Analogues, Patai, S., Ed.; Wiley: New York, 1980; Part
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1383.
Gary W. Breton & Paul J. Kropp
13. (a) Bhatt, M. V.; Kulkarni, S. U., Synthesis 1983, 249. (b)
University of North Carolina, Chapel Hill, NC, USA
Deulofeu, V.; Guerrero, T. J., Org. Synth., Coll. Vol. 1955, 3,
586.
Ronald G. Harvey
14. Vogel, A. I., J. Chem. Soc 1943, 636.
University of Chicago, Chicago, IL, USA
Avoid Skin Contact with All Reagents