IODINE 1
Iodine elements except sulfur, selenium, and the noble gases, although
it does not react directly with carbon, nitrogen, or oxygen.15
Its applications in organic chemistry range from detection of
I2
organic molecules in TLC, to addition reactions with unsaturated
molecules, to reactions as an electrophilic agent with nucleophilic
[7553-56-2] I2 (MW 253.80)
species. Iodine is used not only as an agent for incorporating an
InChI = 1/I2/c1-2
iodine atom but also as an oxidizing agent, a dehydrogenation
InChIKey = PNDPGZBMCMUPRI-UHFFFAOYAF
agent, and as a radiolabel in many biologically important systems.
One of the most common uses of iodine is as a spotting agent
(electrophilic reagent that adds to alkenes1 and alkynes2 to give
for the detection of organic molecules in TLC.11 Many organic
diiodides; alkenyl carboxylic acids react to give iodolactones3
molecules either adsorb iodine vapors or react with iodine vapor
and alkenyl amides lead to iodolactams;4 dehydrogenates amines5
to produce a visible  spot on the TLC plate. In general, basic
and reacts with ketones, in the presence of base, to give
compounds and reducing compounds pick up iodine vapors
ą-iodo ketones;6 carboxylic acids are converted to ą-iodo acid
very well, but acidic compounds and oxidizing compounds do
derivatives7 and carbanions react to give the substituted iodides;8
not.11 Many natural products can be detected via TLC, including
organoboranes can give alkyl iodides9 and vinylboranes lead
steroids,17 phenolic compounds,18 and alkaloids.19
to substituted alkenes;10 important spotting reagent for TLC
analysis11)
Addition to Alkenes. Iodine is a highly polarizable molecule
ć% ć%
that behaves as electrophilic iodine (I+) in the presence of a suit-
Physical Data: mp 113.6 C; bp 185.24 C; d 4.930 g cm-3;
ć%
able Lewis base, such as an alkene or an alkyne. When an alkene
vapor pressure 0.31 mmHg at 25 C.
reacts with molecular iodine, a characteristic iodonium ion is
Solubility: the solubility of iodine, expressed in g/kg of solvent
ć%
formed, and subsequent reaction with the nucleophilic gegenion
at 25 C is: H2O, 0.34; benzene, 164.0; CCl4, 19.2; CHCl3,
(I-) leads to the vicinal diiodide. There are many examples of this
49.7; ethyl acetate, 157; ethanol, 271.7; diethyl ether, 337.3;
type of reaction. Addition of iodine to cyclohexene to give trans-
n-hexane, 13.2; toluene, 1875.12 Soluble glacial acetic acid;
1,2-diiodocyclohexane is a simple example (eq 1).1 The reaction
relatively insol dichloromethane.
127
is believed to involve a radical intermediate, evidenced by for-
Form Supplied in: the natural abundance isotope is I. It is
mation of dimeric coupling products in many alkene iodination
a massive bluish-black solid. When sublimed it forms near
reactions. Reaction of styrene with iodine (neat), for example,
opaque, doubly refractory orthorhombic crystals that have a
gives not only 1,2-diiodo-2-phenylethane but also 1,4-diiodo-2,
metallic luster. Heating iodine generates a violet-colored va-
3-diphenylbutane as a minor product (eq 2).20
por. Commercially available in >99.5% purity, with bromine
and chlorine the primary contaminants. Natural abundance
I
iodine is diatomic, I I.
I2
(1)
Preparative Methods: commercially available but can be pre-
I
pared by the reaction of potassium iodide and copper(II)
sulfate.13 It is also prepared by chlorination of natural brines or
by treatment of brine with silver nitrate and then iron(II) iodide, The iodine reaction can be modified by addition of other
followed by addition of chloride to liberate iodine.14 reagents, such as methanol, to produce iodo ethers. When
Purity: vacuum sublimation. iodine in methanol is reacted with cyclohexene, in the pres-
Handling, Storage, and Precaution: somewhat corrosive.15 It is ence of Cerium(IV) Ammonium Nitrate (CAN), a 92% yield of
stored in a dark bottle or jar, at ambient temperatures. Iodine 2-methoxy-1-iodocyclohexane is obtained (eq 3).21a Similar re-
vapors have a sharp characteristic odor and they are irritating to sults are obtained when iodine and Copper(II) Acetate are
eyes, skin, and mucous membranes (lachrymatory). Prolonged used.21b
exposure should be avoided. Ingestion of large quantities can
I
cause abdominal pain, nausea, vomiting, and diarrhea. If 2 3 g
Ph
of iodine are ingested, death may occur. Ph
Ph I2
+ (2)
neat
I I
Ph
I
Original Commentary
OMe
I2, CAN, MeOH
(3)
Michael B. Smith
50 �C, 6 h
I
92%
University of Connecticut, Storrs, CT, USA
Introduction. Diatomic iodine (I2) is a member of the halo- Iodine reacts with dienes to form a mixture of 1,2-diiodoalkenes
gen family that is widely used in organic chemistry. Iodine is less
and 1,4-diiodoalkenes. When done in the presence of Cop-
electronegative than the other halogens, and iodides are generally
per(I) Cyanide, the 1,4-addition product predominates and 1,
less stable than other halides.16 Oxides of iodine and compounds
3-butadiene thus reacts to give an 84% yield of 1,4-dicyano-
where iodine is in a positive valence state are much more stable
2-butene (eq 4).22 Allenes react with iodine to give diiodides.
than the other halogens. Iodine forms binary compounds with all
When 2,3-pentadiene reacts with iodine in carbon tetrachloride, 2,
Avoid Skin Contact with All Reagents
2 IODINE
O
O
1. Me3SiOTf, NEt3
3-diiodo-3-pentene is formed (eq 5).23 When the reaction is
2. I2, THF
done in methanol, however, 3-methoxy-2-iodo-3-pentene is the
NH2 NH (9)
3. aq Na2SO3
product.
I
CN
I2, CuCN, 85 �C
Addition to Alkynes. Iodine undergoes addition reactions
(4)
Parr reactor, heptane
with alkynes as well as alkenes, although the reaction is gen-
84%
erally more sluggish. Reaction of 1,4-dichloro-2-butyne with
CN
iodine, for example, requires 1,2-dichloroethane as a solvent
ć%
and heating to 83 C for 120 h to give (E)-1,4-dichloro-2,
MeO I
3-diiodo-2-butene (eq 10).27 Treatment of this alkene with 1,
I2, MeOH I2, CCl4 8-Diazabicyclo[5.4.0]undec-7-ene leads to formation of iodo-
(5)
"
dienes. Another example is 1-hexyne, which reacts with iodine
I I
in methanol to produce (E)-1,2-diiodo-1-hexene (eq 11).2 When
Silver(I) Nitrate is added to this mixture, however, a mixture of
There are two very interesting and useful variations of the
1,1-diiodo-2-hexanone, 1-iodo-1-hexyne, and (E)-1,2-diiodo-1-
fundamental addition reactions to alkenes: iodolactonization3 (to
hexene is formed (31%, 46%, 23% yields).15
form iodolactones) and iodolactamization (to produce iodolac-
I
tams). When an alkenyl acid reacts with iodine in the presence
Cl Cl I2, ClCH2CH2Cl
DBU, PhH
Cl
of a base (such as sodium bicarbonate), the initially formed iodo-
Cl
83 �C, 120 h 20 �C, 71%
nium ion reacts with the carboxylate anion (generated in situ) to
I
86%
form the iodolactone (eq 6).
Cl
I
O
O
(10)
I2, NaHCO3
I
O
OH
I+
Cleavage of Cyclopropanes. Iodine also reacts with cyclo-
O
propanes, leading to ring opening and formation of a diiodide.28
O
(6)
The cyclopropane ring in benzocyclopropanes, for example, reacts
I
with iodine to produce the diiodide (eq 12). Cyclopropylcarbinyl
systems are opened by iodine, and when a leaving group is avail-
Lactones are also formed when iodine reacts with alkenyl
able, such as trimethyltin, an alkenyl iodide is formed (eq 13).
amides or alkenyl carbamates. In initial studies, amides led to the
formation of lactones whereas carbamates gave oxazolidinones.
I
I2
When N-(S)-phenethyl-2-allyl-4-pentenamide reacts with 3 equiv
of iodine in aqueous THF, a 77% yield of 2-allyl-5-iodomethyl- MeOH
�-butyrolactone is obtained (16% optical purity) (eq 7).24 Simi- I
larly, reaction of N-Cbz-N-methyl-2-propenamine with iodine in
Bu
dichloromethane leads to a 95% yield of N-methyl-4-iodomethyl-
2-oxazolidinone (eq 8).25
MeOH
(11)
AgNO3
3 equiv I2, aq THF 89%
(7)
O I
77% (16% optical yield)
O
O
(S)
HN I
O
+ I Bu +
Ph I
I I
O
O 31 : 46 : 23
1. I2, rt, CH2Cl2
Me
N O Ph N O (8)
2. Na2S2O3
I2, rt
I
Me
(12)
I
I
The more difficult lactam forming reaction (iodolactamization)
can be accomplished by treatment of primary alkenyl amides with
I2, CDCl3, 20 �C
Me3Sn I
SnMe3 I + (13)
Trimethylsilyl Trifluoromethanesulfonate, followed by iodina-
>90%
tion, as in the conversion of 4-pentenamide to 5-iodomethyl-2-
pyrrolidinone in 68% yield (eq 9).4 There are several other cy-
clization reactions that are initiated by the reaction of iodine with Conversion of Alcohols to Iodides. Alcohols react with io-
an alkene, in the presence of a nucleophilic atom elsewhere in the dine and red phosphorus to produce a phosphorus iodide, in situ.
molecule.26 Phosphorus iodides have poor shelf lives (they are unstable and
A list of General Abbreviations appears on the front Endpapers
IODINE 3
decompose under mild conditions) and are prepared immediately concentration of the ketone substrate is increased, the yield of
prior to use. An example is the conversion of cetyl alcohol to cetyl the hydroxy ketone is diminished and a dimer is formed, 1,2,3,
iodide in 85% yield (eq 14).29 This is the most common method 4-tetraphenyl-1,4-butanedione (47% yield at 0.2 M).34
for the conversion of aliphatic alcohols to aliphatic iodides.
O
2 equiv P (red)
3 equiv I2
I
(14)
C15H31 OH C15H31 I
150 �C
HO
I2
NaOMe
Reaction with Amines. Dehydrogenation is another impor-
O
0 �C, N2
MeOH
tant reaction of iodine, and it is particularly useful for generation
of enamines. Reaction of nuciferine with iodine, in dioxane con-
O
taining sodium acetate, leads to an 87% yield of the enamine
2 equiv I2
dehydronuciferine (eq 15).30 Amines in general lead to enamines, NaOMe, N2
I
HO
0 �C
as in the conversion of triethylamine to N,N-diethylvinylamine
I
MeOH
(eq 16).5 This reaction can be applied to many systems.31 For
systems that do not contain an amino moiety, e.g. arenes such
HO (18)
ć%
as ethylbenzene, a flow reactor and high temperatures (650 C)
are required for dehydrogenation. This particular example uses
Ph
a molten Lithium Iodide reactor to convert ethylbenzene to the
OH
O
I2, NaOMe
alkene product, styrene, in 96% yield (eq 17).32
Ph Ph Ph
Ph Ph ++ PhCO2Me
Ph
25 �C
O O
O
MeO MeO
(19)
Ph
N N
trace trace
0.0071 M 99%
I2, dioxane
MeO
MeO Me Me
47% 3%
0.2 M 46%
(15)
reflux, NaOAc
The iodoform reaction clearly shows that iodine behaves as
an electrophile in the presence of enolate anions, particularly
enolate anions of carboxylic acid derivatives. When 6-heptenoic
acid is treated with 2 equiv of Lithium Diisopropylamide, and
I2
(16)
N N N
then quenched with iodine, a 70% yield of 2-iodo-6-heptenoic
+
acid is obtained (eq 20).7 In this particular reaction, 12% of the
dicarboxylic acid 2,3-di-4-pentenyl-1,4-butanedioic acid is also
I2, 650 �C, O2
obtained, leading to the belief that radical anions are produced
(17)
molten LiI
in this reaction.7 Such coupling reactions are also observed with
flow apparatus
esters which form succinic acid ester derivatives, as in the reac-
tion of ethyl 2-methylpropanoate with 2 equiv of LDA and subse-
quent reaction with iodine to give an 85% yield of diethyl 2,2,3,
Reactions with Ketones, Aldehydes, and Carboxylic Acid
3-tetramethyl-1,4-butanedioate (eq 21).35
Derivatives. Iodine reacts with ketones as well as with alkenes.
The reaction is usually done in the presence of base and proceeds 1. 2 equiv LDA
CO2H
via the enolate anion. This is the fundamental process that occurs
2. I2
in the Lieben iodoform reaction,33 in which a methyl ketone reacts
CO2H
I
with iodine and sodium hydroxide to give iodoform (CHI3) with
+ (20)
oxidative cleavage of the methyl group to produce a carboxylic
CO2H
CO2H
acid. The H3C C bond of methyl carbinols [RCH(OH)Me] is also
70% 12%
cleaved with this reagent to give the corresponding acid and iod-
1. 2 equiv LDA, THF
CO2Et
oform. The iodoform reaction constitutes a classical test for the
 78 �C
CO2Et (21)
presence of a methyl ketone moiety or a methyl carbinol moiety
2. I2,  78 �C
CO2Et
in an unknown molecule.
85%
Oxidative cleavage is not always the case in this reaction, espe-
cially when sodium methoxide is substituted for sodium hydrox- Carboxylic acid derivatives can react with iodine without an
ide. Steroidal ketones react with iodine and sodium methoxide to intermediary enolate anion to produce ą-iodocarboxylic acids.
give a 58% yield of the ą-iodo ketone, when air is excluded from ą-Iodocarboxylic acid chlorides can also be produced, as when
ć%
the reaction (eq 18).6 When oxygen is introduced, an 85% yield hexanoic acid reacts with iodine and Thionyl Chloride, at85 C, to
of the ą,ą-diiodo ketone is produced.6 Reaction of aryl ketones give an 80% yield of 2-iodohexanoyl chloride (eq 22).36 Similarly,
can lead to a different result. 1,2-Diphenyl-1-ethanone reacts with butanoic acid reacts with Chlorosulfonic Acid and iodine to give
iodine and sodium methoxide at low concentrations to give a 99% a 94% yield of 2-iodobutanoic acid (eq 23).37 These examples are
yield of 1,2-diphenyl-2-hydroxy-2-ethanone (eq 19).34 When the nothing more than the iodine analog of the Hell Volhard Zelinsky
Avoid Skin Contact with All Reagents
4 IODINE
reaction.38 The silver salt of pentanoic acid reacts with iodine to butyllithium and iodine, to give a 71% yield of the 4-iodofuran-
produce 1-iodobutane in 67% yield, where decarboxylation occurs 3-carboxylic acid (eq 29).44
under the reaction conditions (eq 24).39 In general, alkyl iodides
are formed from silver carboxylates. This is the iodine version
CO2H I CO2H
1. 2.2 equiv BuLi
of the Hunsdiecker reaction.40 Similar reaction occurs when mer-
 20 �C, 1 h
(29)
cury(II) oxide is added, although the yield is lower.
TBDMS TBDMS
2. I2, THF, MgBr2
O O
3. 10% HCl
O O
1. I2, SOCl2, 85 �C 71%
90 min
OH Cl (22)
2. Na2S2O3
I Simple aromatic derivatives can be iodinated to generate iodo-
substituted aromatic compounds, if activating substituents are
O O
present on the aromatic ring. 1,3-Dicyanobenzene, for example,
0.5 equiv I2, ClSO3H
OH Cl (23)
reacts with LDA and iodine to give a 79% yield of 2-iodo-1,3-
ClCH2CH2Cl, 80 �C
I
dicyanobenzene (eq 30).45 In general, unactivated aromatics are
94%
less useful since formation of the requisite carbanion is somewhat
I2 67%
more difficult.
CO2 Ag+ I (24)
I2, HgO 36%
CN CN
CN
I2
LDA, THF
Li (30)
I
 96 �C, 3 min 79%
Iodination of Aromatic and Heteroaromatic Compounds.
CN CN
Just as enolate anions react with the electrophilic iodine, so also CN
other carbanions react. Iodoimidazoles can be formed, as when
N-tritylimidazole reacts with Butyllithium and then with iodine,
Conversion of Organoboranes to Iodides. Another impor-
to give a 41% yield of 2-iodo-N-tritylimidazole (eq 25).8
tant area of chemistry where iodine reactions are important in-
1. BuLi volves organoboranes. When an alkene is reacted with a borane
Ph Ph
N N N N
(25)
2. I2, THF to produce a trialkylborane, subsequent reaction with iodine and
Ph Ph
Ph Ph
41%
I
sodium hydroxide leads to an iodoalkane. 1-Decene reacts with
tri-n-butylborane and then basic iodine to give a 65% yield of
Iodoindoles can also be produced by this approach. Reaction
1-iododecane (eq 31).9
of indole with n-butyllithium and quenching with iodine first pro-
duces an N-iodoindole, but this is unstable and rearranges un-
1. Bu3B
I
der the reaction conditions to 3-iodoindole, in near quantitative
2. I2, NaOH
(31)
yield (eq 26).41 When this iodo derivative is converted to the
65%
N-phenylsulfonyl derivative, reaction with LDA and then iodine
gives a 98% yield of 2,3-diiodo-N-phenylsulfonylindole.41
Substituted alkenes can also be prepared from vinylboranes
by reaction with iodine and sodium hydroxide. Reaction of dicy-
I I
clohexylborane with 1-hexyne gives the vinylborane, and subse-
1. BuLi
(26)
PhSO2Cl
1. BuLi quent reaction with basic iodine, in THF, gives a 93:7 cis:trans
I
2. I2 2. LDA, THF mixture of 1-cyclohexyl-1-hexene in 85% yield (eq 32).10 When
N N N
 78 �C
the reaction is done in dichloromethane, a 77:23 cis:trans mix-
H H
SO2Ph
3. I2
ture is produced, but in only 13% yield.10a The poor yield
is probably due to the poor solubility of iodine in dichloro-
Iodopyridine derivatives can also be generated with this tech-
methane.
nique. 3-Fluoropyridine reacts with LDA and iodine to give a 50%
yield of 4-iodo-3-fluoropyridine (eq 27),42 and 2-chloropyridine
reacts with n-butyllithium and then iodine to give a 60% yield of I2, NaOH
B
2-chloro-3-iodopyridine (eq 28).43
THF
85%
I
F F
1. LDA, THF,  78 �C
(27)
2. I2
N N + (32)
50%
I
1. t-BuLi, THF,  70 �C
7 : 93
(28)
2. I2,  70 �C
N Cl N Cl
60%
Miscellaneous Reactions. There are several specialized re-
Iodofuran derivatives can be formed, as in the reac- actions of iodine that are useful in certain applications. Io-
tion of 2-(dimethyl-t-butylsilyl)furan-3-carboxylic acid with n- dine induces coupling of sodium cyclopentadienide to form
A list of General Abbreviations appears on the front Endpapers
IODINE 5
CO2Me
9,10-dihydrofulvalene.46 Iodine has also been used to cleave CO2Me
1. Ti(Oi-Pr)4, CH2Cl2
iron carbon bonds in organoiron species.47 Iodine reacts with hy-
CO2Me
2. 1.5 equiv I2, rt, 2 h
CO2Me
drazone derivatives to give vinyl iodides.48
I
74%
Reaction with Organic Halides. An important reaction of io-
(33)
dine is exchange with an alkyl iodide. The most common method
for exchanging an iodide is the Finkelstein reaction,49 which in-
Iodine reacts with an alkene and an alcohol, in the presence
volves treatment of alkyl halides with Sodium Iodide to produce
of cupric acetate in dioxane, to give an iodohydrin.65 In the
alkyl iodides via an SN2 reaction. Reaction of 1-bromobutane and
presence of Ce (IV) triflate, alkenes react with I2 and an alco-
sodium iodide in dry acetone, for example, gives 1-iodobutane.
hol to give the iodohydrin.66 Cyclohexene reacts with methanol
This exchange also occurs with alkyl iodides. The metal io-
and iodine, for example eq 34, to give an 80% yield of trans-
dides used in this reaction are commercially available, but can be
methoxyiodocyclohexane. In the absence of Ce(OTf)4, the re-
prepared from iodine.
action gave only 10% of product after 5 days. Iodohydrins
Iodine itself is capable of exchanging the halide atom in alkyl
are also formed when alkenes react with a mixture of I2 and
halides, including alkyl iodides, to produce alkyl iodides. The re-
phenyliodine(III) bis(trifluoroacetate) in aqueous acetonitrile at
ć%
action temperatures required are usually greater than 150 C.50
-15ć%C.67
Aryl iodides undergo this exchange reaction at even higher tem-
ć%
peratures (150 190 C).51 ą-Iodo ketones also react with iodine,
I
but this occurs at ambient temperatures.52 The product of these
0.75% I2, MeOH, rt
(34)
reactions is, of course, another iodide but this is very important
0.25% Ce(OTf)4, dixane
OMe
in radiolabeling using radioactive iodine isotopes. All of the re-
actions of iodine involve the use of the natural abundance stable
80%
127
isotope of iodine, I. Radiolabeled molecules can be incorpo-
Iodination of alkynes generally gives primarily the trans-diio-
rated in a wide range of biological and mechanistic studies. There
dide,68 but the reaction is sometimes slow, giving poor yields.
are at least 10 available isotopes of iodine, but only three are
123 125 131
Iodination of terminal alkynes in methanol has been reported,69
commonly used for labeling: I, I, and I. If these isotopic
and Al2O3 can catalyze the iodination of electron-rich alkynes
iodines are used in the preceding reactions, radiolabeled iodides
are produced. In the case of the Finkelstein reaction, sodium io- such as 1-hexyne.70 This latter variation does not work well for
electron-deficient alkynes. Cuprous iodide is a good catalyst for
dide or Potassium Iodide can be produced by synthesizing those
the iodination of terminal alkynes.71 Treatment of 1-phenylethyne
salts with radiolabeled iodine. A variety of organic molecules
with I2 and CuI in eq 35, for example, gave a 95% yield of the
have been radiolabeled for use in biological studies. These include
diiodide.71
fatty acids,53 aniline derivatives,54 quinolines,55 nucleic acids,56
steroids,57 alkyl iodides,58 aryl iodides,59 carboxylic acids,60 and
Ph I
I2, CuI, 3.5 h
carbohydrates.61
Ph C C H (35)
MeCN, 60 �C
I H
95%
First Update
Iodine reacts with dienes to form a mixture of 1,2-diiodoalkenes
and 1,4-diiodoalkenes. Iodine adds to allenes to give iodomethyl
Michael B. Smith
vinyl iodides, and addition to 1,1-disubstituted allenes gives
University of Connecticut, Storrs, CT, USA
the more highly substituted and thermodynamically more stable
alkene.72 This addition is solvent dependent, and equilibration
Iodine is known to form polyvalent I2 compounds, and a variety
of chemical transformation are available from these compounds.62 occurs to give the more stable product. In the example shown in
eq 36, addition of I2 and equilibration over 3 h gave a 13:1 Z:E
The focus of this review is on I2 itself, sometimes in conjunction
mixture from a 0.8:1 Z:E mixture of the initial addition product.73
with additives, to initiate chemical transformations.
Addition to Alkenes and Alkynes. In the presence of an
TBDMSO TBDMSO I
I2, 3 h
electron-donating alkene or alkyne, I2 reacts to form an inter- (36)
C I
CDCl3
C7H15 C7H15
mediate iodonium ion, which reacts with the iodide counterion
to give a vicinal diiodide. The addition of I2 to cyclic alkenes
gives the trans-diiodide. Addition of I2 to cyclohexene to give A variation of the iodination reaction generates an iodonium
trans-1,2-diiodocyclohexane is a simple example (eq 1).63 Such intermediate in the presence of a nucleophilic atom, generating
iodination reactions can be used in conjunction with other reac- five- and six-membered ring heterocyclic compounds. Alkene
tions. Alkenyl and alkynylmalonate derivatives undergoes reac- precursors can be used as well as alkyne precursors. Iodopyrro-
tion with transition metal compounds, and subsequent reaction lines,74 iodopyrrolidines,75 iodopyrrolidinones,76 and iodote-
with I2 leads to iodocarbocyclization.64 In eq 33, initial reaction trahydrofuran derivatives77 have been prepared by iodine-induced
with tetrakis(isopropoxy)titanium in CH2Cl2, followed by reac- cyclization. An example of the latter reaction is treatment of keto
tion with 1.5 equiv of I2 at ambient temperatures gave a 74% yield esters, such as the one shown in eq 37, with I2 in the presence
of the iodomethylcyclopentane derivative.64 of sodium carbonate.77 Cyclization via the enol or enolate form
Avoid Skin Contact with All Reagents
6 IODINE
H
of the keto ester in eq 37 gave the iodotetrahydrofuran in 84%
H
yield.77 Similar cyclization of alkene acetals led to the transfor-
I2, MeCN, rt
I
(41)
O
mation of 1,2-diols to the iodomethyltetrahydrofuran derivative
O
(86% yield) in eq 38.78 Cyclization of 3-alkynyl-1,2-diols with SO2Np
O
O
3 equiv of I2 and NaHCO3 gave good yields of 3-iodofurans.79
Cyclization of o-acetoxy and o-benzyloxyalkynylpyridines with
I2 and NaHCO3 gave 2,3-disubstituted furopyridines.80 The ap-
proach has been used to synthesize 4-iodoisoquinolines81 via an
Iodoaziridines can be prepared by a modification of the cy-
alkyne derivative. Reaction of the imine-alkyne in eq 39 with ex-
clization strategy just shown. Treatment of N-tosylallylamine with
cess I2 led to the vinyl diiodide. In the presence of the base, a 68%
potassium tert-butoxide and then iodine in toluene gave a 94%
yield of the isoquinoline was obtained.81 Homopropargylic sul-
yield of the iodoaziridine (eq 42).88 Another aziridination reaction
fonamides undergoes iodine-induced cyclization to give 4-iodo-
involves the iodine-catalyzed reaction of alkenes with chloramine-
2,3-dihydropyrroles.82
T.89 In eq 43, 1-octene reacted with Chloramine-T and I2 to give
a 67% yield of the N-tosylaziridine.89
O
CO2Et
I2, Na2CO3, CH2Cl2 O
t-BuOK
NHTs
I
toluene
rt, 9 h CO2Et
84%
(37)
I2
- NTs
I
NTs K (42)
OH
HO
I2, Na2CO3, MeCN Ts
O
HO
I
0.5 equiv Chloramine-T, 10% I2 N
0 �C, 15 min
C6H13
MeCN, rt, 1 d
OBn C6H13
OBn
(43)
67%
(38)
86%
Yet another variation of this iodocyclization procedure prepared
N 8 equiv I2, MeCN phosphaisocoumarins.90 Reaction of the alkynyl phosphonate in
N
(39)
eq 44 with 2 equiv of iodine in chloroform at ambient temperatures
3 equiv NaOCO2Me
Ph
30 min, 25 �C gave an 83% yield of the phosphaisocoumarin.90
Ph 68% I
Ph
I
Iodolactonization83 is an often used variation of this ring-
Ph
2 equiv I2, CHCl3
forming protocol (eq 6) that continues to be important. In a synthe-
(44)
OEt
rt, 12 h
sis of (-)-cinatrin B,84 alkene-acid (eq 40) formed an iodonium
P
P
carboxylate during the course of the reaction with I2 and NaHCO3, OEt
OEt
O
O
leading to a 97% yield of the iodolactone with 88% ds. A vari-
83%
ation of this cyclization reaction used an ester. In a synthesis of
( + )-epoxyquinol A,85 the ester shown in eq 41 was treated with
iodine, and an 81% yield of the iodolactone was obtained (>99%
ee after crystallization). Iodolactonization of allene-acids leads
Reaction with Arenes. Iodination of aromatic compounds is
to �-iodobutenolides.86 Another related reaction treated alkenyl
possible (eqs 25 30). In some cases, direct iodination is possible
carbonates (OCO2t-Bu) with I2 to produce iodomethyl cyclic
without the need for additives. In a synthesis of demethylaster-
carbonates.87
riquinone B1 by Pirrung and co-workers,91 the indole unit reacted
with I2 faster than the trisubstituted alkene substituent to give a
69% yield of the iodoindole (eq 45) after Boc protection of the
OBn
BnO
I2, NaHCO3
nitrogen.
ether-H2O
C9H19
MeO
O
OH
I
O
OBn
BnO
I
(45)
1. I2
N
N
C9H19 (40)
2. Boc2O, DMAP
MeO
O H
H
O
O
69%
A list of General Abbreviations appears on the front Endpapers
IODINE 7
In most cases, an additive is required to convert arenes to the of aryl iodides. When 1-phenyl-3-pyrrolidinetriazine reacted with
ć%
corresponding aryl iodide. In combination with nitrogen diox- I2 in diiodomethane at 8 C, in eq 50, >98% of iodobenzene was
ide, I2 converts arenes to the aryl iodide.92 As shown in eq 46, obtained.99 Dialkyltriazenes of this type are prepared from the cor-
toluene was converted to a 60:40 mixture of 4-iodotoluene and responding aryldiazonium salt.101 Aniline derivatives and other
2-iodotoluene with I2 and NO2 catalyzed by sulfuric acid in 60% aromatic amines are treated with nitrous acid (typically formed
yield.92 A mixture of I2 and HgO can be used for the prepa- in situ with NaNO2 and HCl) to give the aryldiazonium salt.
ration of aryl iodides,93 and mercuric nitrate can be used as Subsequent reaction with a secondary amine gives the triazene.
well.94 The triazene used in eq 50 was prepared from benzenediazonium
chloride and pyrrolidine.99,101
Me Me
Me
I
0.5 equiv I2, excess NO2 CHCl3
+ I2, CH2I2, 80 �C, 4 h
5% H2SO4, 60 �C, 4 h
N N N I
I (46)
>98%
(50)
60% 40%
In the presence of certain oxidants, I2 reacts with arenes to
give the corresponding aryl iodide. Potassium permanganate and
Cleavage of Epoxides. The reaction of I2 and an epoxide
manganese dioxide have been used95 as well as tetrabutylammo-
in the presence of certain catalysts leads to the corresponding
nium peroxydisulfate.96 In eq 47, this latter reagent converted
iodohydrin. Iodine and a crown ether open epoxides to give the
dimethoxybenzene to the 2-iodo derivative in 92% yield.96
iodohydrin.102 Both phenylhydrazine103 and 2,6-bis[2-o-amino-
phenoxy)methyl]-4-bromo-1-methoxybenzene104 have been used
as catalyst. In eq 51, cyclohexene oxide reacted with I2 in the
O
O
presence of 10% phenylhydrazine to give a 95% yield of the
O +NBu4
OMe OMe
O S
S O
iodohydrin.103 Iodine also opens epoxides in combination with
Bu4N+  O
I
O
O manganese(salen) complexes.105
(47)
I2, MeCN, 3 h, 20 �C
92%
OH
OMe OMe
I2, 10% PhNHNH2
O (51)
CH2Cl2, 25 �C, 2.5 h
I
95%
In combination with sodium periodate and sulfuric acid, I2 re-
acts with arenes to form the corresponding aryl iodide. Benzene
reacted as shown in eq 48, for example, to give a 65% yield of
iodobenzene.97 Similarly, carbazole reacted with I2 under these Cleavage of Cyclopropanes. Iodine reacts with cyclo-
conditions to give a 75% yield of the aryl iodide (eq 49).98 propanes (eq 13), leading to ring opening and formation of a
diiodide.106 An interesting example of this reaction involved I2
with hexafluorocyclopropane.107 As shown in eq 52, heating I2
ć%
I2, NaIO4, H2SO4
and hexafluorocyclopropane to 155 C in a Shaker rube gave
I
(48)
AcOH, Ac2O
an 80% yield of the mixed halide 1,1,2,2,3,3-hexafluoro-1,3-
diiodopropane.107
65%
F
F F
F
I2, 155 �C
F F
F
F (52)
I I I
F F
F F
I2, NaIO4, cat H2SO4
80%
EtOH, 65 �C, 1 h
N
N
H (49)
H
The reaction is not restricted to simple cyclopropane deriva-
tives. Cyclopropylcarbene chromium complexes react with I2 to
75%
form 1,4-diiodo-1-alkenes.108 Two examples are shown that illus-
trate the diversity of the process. In eq 53, the bicyclo[4.1.0]hept-
Iodine has been shown to promote the decomposition of 1- anethiocarbene complexes were opened with I2 to give the
aryl-3,3-dialkyltriazenes.99 Previous work reported the thermal diiodo compound shown in 87% yield as a 78:28 Z:E vinyl sul-
decomposition of triazines,100 but there were problems associated fide mixture.108 In the second example (eq 54), opening the cy-
with the requisite high temperatures. The addition of I2 diminished clopropyl(methoxy)carbene complex gave an intermediate that
the reaction temperature, and increased the yield of the aryl io- generated methyl 4-iodobutanoate as the final product in 41%
dide. This protocol constitutes a mild procedure for the synthesis yield.108
Avoid Skin Contact with All Reagents
8 IODINE
H
SPh
I2, CH2Cl2, -20 �C
Ph3BiBr2, I2
Cr(CO)5 OH
+
45 �C, 3 h
H
I
Ph Ph
Ph
I
(58)
(53)
73%
8%
SPh
A related reaction converts 1,2-diols to the corre-
87% (78:28 Z:E)
sponding alkene. Pedro and co-workers, in a synthesis
I
OMe of plagiochiline N,114 reacted a diol unit (eq 59) with
O
I2, CH2Cl2,  20 �C
chlorodiphenylphosphine iodine115 followed by hydrogen
(54)
Cr(CO)5
peroxide acetic acid/THF, and obtained a 70% yield of the
OMe
alkene.
41%
Reaction of Alcohols with Iodine. Alcohols are converted
OTBS
directly to the corresponding alkyl iodides in poor to moderate
H
1. Ph2PCl I2
yield by simply heating the alcohol with I2 in an alkane solvent.109
2. H2O2, AcOH-THF
TBDMSO
2(S)-Octanol was heated with I2 (eq 55), but 2(R)-iodooctane was
obtained in only 25% yield. The reaction proceeds largely with
H
OH
inversion of configuration, although the inversion does not appear OH
OTBS
to be complete.
H
I2, Pet. ether, reflux, 6 h
TBDMSO (59)
25%
OH
I
H
(55) 70%
Another useful protocol involves conversion of alcohols to
Iodine and Amines. Iodine catalyzes the reduction of diaryl
iodides with triphenylphosphine and iodine. In a synthesis of
alkenes in the presence of 50% aq H3PO2 in acetic acid.116 In
( + )-discodermolide,110 Smith and co-workers treated the alcohol
eq 60, dibenzosuberenone was reduced to dibenzocycloheptane,
shown in eq 56 with triphenylphosphine, imidazole, and iodine in
and this reagent reduced both the alkene unit and also deoxy-
1:2 benzene:ether and obtained a 95% yield of the primary iodide.
genated the ketone moiety.117 The active reducing agent for this
system was reported to be hydrogen iodide.117 This observation
OH I
was extended to include diaryl alkenes such as trans-stilbene,
PPh3, imidazole, I2
which gave a 99% yield of 1,2-diphenylethane under these
O O OTBS PhH:ether (1:2) O O OTBS
reaction conditions.116
PMP PMP
O
95%
(56)
H3PO2, AcOH, heat
cat I2
Modification of this procedure allows the formation of alkenes
from cyclopropylcarbinyl alcohols. In a synthesis of (-)-doli- (60)
culide,111 Ghosh and Liu treated the cyclopropylcarbinyl alco-
hol shown in eq 57 with triphenylphosphine, imidazole, and I2
Iodination Involving Carbonyl Compounds. Iodine reacts
to give the corresponding iodide.111 Subsequent treatment with
with ketones to produce ą-iodoketones. ą-Iodoenones can be pre-
n-butyllithium in the presence of TMEDA and molecular sieves
ć%
pared, but a catalytic amount of amine must be added,118 although
at -78 C gave a 72% yield of the alkene. This protocol was
ammonium salts can also be used. Solvent plays a significant role
reported earlier by Charette and co-workers.112
in this reaction.119 In the presence of the activating salt shown in eq
HO
61, I2 reacts with 4-hydroxyacetophenone to give the iodomethyl
compound in 78% yield when methanol was used as the solvent.
1. PPh3, imidazole, I2
When the same reaction was performed in acetonitrile, however,
2. BuLi,  78 �C
(57)
a 72% yield of 3-iodo-4-hydroxyacetophenone was recorded.
BnO BnO
Cl
F N N
O
72% O 2 BF4
HO
HO
I2, MeOH
I
A general application of this dehydration sequence treats sec-
78%
ondary and tertiary alcohols with Ph3BiBr2 and I2 to give the
(61)
more stable alkene in good yield.113 Reaction of the cyclohexanol
derivative in eq 58, for example, gave a 73% yield of the cyclo- Iodination has been accomplished with I2-(NH4)2
hexane derivative with only 8% of the cyclohexylidene derivative Ce(NO3)6.120 This reagent converted cyclohexanone to 2-
being formed.113 iodocyclohexanone in 94% yield as shown in eq 62.120 ą-Iodo
A list of General Abbreviations appears on the front Endpapers
IODINE 9
aldehydes have been prepared in good yield by treatment of silyl the 3-iodopyridine derivative.127 This reaction is shown in
enol ethers with I2 and AgOAc.121 eq 67.
O O
I
LiN(i-Pr)2, I2, -78 �C
I
(67)
CAN, AcOH/H2O
O O
(62)
I2, 50 �C N N
N(i-Pr)2 N(i-Pr)2
94%
80%
In 1962, Barton and co-workers described reactions of hydra-
Another example, taken from a synthesis of caerulomycin E,128
zones with iodine. Ketone hydrazones reacted with I2 to give vinyl
treated the pyridine oxide in eq 68 with LDA and then I2 to give
iodides, but aldehyde hydrazones gave gem-diiodides.122 A later
a 70% yield of the 6-iodo compound.
study by Pross and Sternhell showed that the relative amounts of
amine and ether solvents played a significant role in the product
distribution.123 In 1983, Barton and co-workers introduced an im-
provement to this procedure that greatly improved the yield and
N
N
1. LDA, THF, -70 �C
N+
I N+
selectivity of the reaction.124 The reaction of the ketone hydrazone (68)
2. I2
O
in eq 63 (from the reaction of the ketone with hydrazine) with the O
- -
azine base in ether gave an 89% yield of the vinyl iodide.124 When
70%
isobutyraldehyde was subjected to the same conditions, however,
a 70% yield of the gem-diiodide was obtained (eq 64).124
Organoboranes are converted to the corresponding iodide with
These procedures have found their way into the synthesis of
iodine, as in the reaction of 1-decene with tri-n-butylborane and
natural products. In a synthesis of ( + )-norrisolide by Theodorakis
then basic I2, to give a 65% yield of 1-iododecane (eq 31).129
and co-workers,125 the bicyclic ketone in eq 65 was treated with
(2-Stannylalkenyl)boranes are similarly converted to the vinyl io-
hydrazine to give an 88% yield of the hydrazone, and then reaction
dide by treatment with I2 in THF and then with acetic acid.130
with I2 and NEt3 gave a 62% yield of the vinyl iodide.
When alkenylcatecholboranes are treated with a Grignard reagent,
I
O
subsequent treatment with iodine induces rearrangement and
Nt-Bu
oxidation to give Z-alkenes.131 In eq 69, conversion of 1-decyne
3.5 equiv
Me2N NMe2
to the vinyl catecholborane was followed by reaction with butyl-
I2, ether, rt
magnesium bromide and then I2/NaOH to give a 60% yield of
MeO
MeO
Z-5-tetradecene.131 Substituted alkenes can also be prepared from
89%
vinylboranes by reaction with I2 and NaOH. Reaction of dicyclo-
(63)
hexylborane with 1-hexyne gives the vinylborane, and subsequent
Nt-Bu
reaction with basic I2 in THF gives a 93:7 cis:trans mixture of
O I
1-cyclohexyl-1-hexene in 85% yield.132
3.5 equiv Me2N NMe2
(64)
H I
I2, ether, rt
O
B H
70%
O
O
I
C8H17
Me Me
1. N2H4
(65)
2. I2, NEt3
C8H17
H H
C8H17 Bu
B 1. BuMgBr, THF
62% O
(69)
O 2. I2, NaOH, THF
60%
Formation of gem-diiodides has also been used in synthesis. In
a sphingosine synthesis by Griengl and co-workers,126 tetrade-
canal was converted to the hydrazone with hydrazine hydrate
in eq 66, and subsequent treatment with I2 and NEt3 gave 1,
Acyliron complexes are converted to esters upon treatment with
1-diiodotetradecane, but in only 25% yield.
I2 in alcohol solution.133 In eq 70, addition of I2 and benzyl alcohol
to the acyliron complex gave a 59% of the corresponding benzyl
H I
1. N2H4 hydrate
C12H25 C12H25
ester.133
(66)
2. I2, NEt3
O I
PhCH2OH, I2, MeCN
Fe(CO)[(NO)dppe]
25%
rt, 3 h
O
Iodination of Organometallic Compounds. In a synthe-
OCH2Ph
(70)
sis of carerulomycin C, treatment of the pyridine amide shown
O
with lithium diisopropylamide generated the ortho-lithiated com-
59% (66:34 E:Z)
pound, which reacted with I2 to produce an 80% yield of
Avoid Skin Contact with All Reagents
10 IODINE
Zirconacyclopentenes are converted to iodoalkenes upon treat- nitriles.156 Thiols were converted to disulfides by treatment with
ment with I2, in what is known as the Negishi zirconation iodin- I2 and morpholine.157
ation protocol.134 In a synthesis of furanocembranolides,135 Pa-
Me
Me
quette and co-workers added a metal and a methyl group to the
MeO2C
MeO2C
alkyne in eq 71, using dichlorobis(cyclopentadienyl)zirconium
6 equiv NaOEt, 2 equiv I2
and trimethylaluminum, and then reacted the vinylzirconate with
EtOH,  78 �C
I2 to give the vinyl iodide. O
OH
I
1. Cp2ZrCl2, AlMe3
Me
66%
ClCH2CH2Cl, 0 �C
Me3Si Me3Si I (71)
(73)
2. I2, THF, -30 �C
In the presence of an excess of sodium ethoxide and 2
This sequence is highly selective for reaction of alkynes rather
equiv of iodine, 2-cyclohexenones that contain an electron-
than alkenes, as illustrated by a synthesis of curacin A,136 in which
withdrawing group undergoes aromatization to the corresponding
White and co-workers treated the terminal alkyne shown in eq
iodophenol.158 In eq 73, the cyclohexenone derivative shown was
72 with dichlorobis(cyclopentadienyl)zirconium and trimethyl-
converted to the iodophenol in 66% yield.158
aluminum. Subsequent reaction with I2 gave a 69% yield of the
In the presence of 2 equiv of indium, I2 promoted radical cy-
vinyl iodide without disturbing the terminal alkene moiety.
clization of certain substrates.159 In eq 74, the iodo allyl ether
1. Cp2ZrCl2, AlMe3 reacted with I2 and indium in methanol, via radical cyclization,
Me
CH2Cl2
to give an 87% yield of benzofuran after a second step involving
I
2. I2, THF
reaction with 2 equiv of H2O2.159
OMe
OMe
69%
(72)
I
I
1. 2 equiv In, I2, DMF, rt, 4 h
(74)
2. 2 equiv H2O2, rt, 0.5 h
Iodine in the Protection/Deprotection of Various Functional O
O
Groups. Alcohols are converted to the O-acetate with catalytic
87%
I2,137 and acetals are produced from aldehydes.138 Acetals139 and
dithioacetals140 have been produced with this protocol. However,
dithioacetals are converted back to the carbonyl compound by
Related Reagents. Dimethyl Sulfoxide Iodine; Iodine Alu-
treatment with I2 silver nitrite.141 Dithioacetals can be converted
minum(III) Chloride Copper(II) Chloride; Iodine Cerium(IV)
to the corresponding dioxolane with I2 in 1,2-ethanediol.142 In ad-
Ammonium Nitrate; Iodine Copper(II) Acetate; Iodine
dition, I2 was shown to catalyze esterification of carboxylic acids
Copper(I) Chloride Copper(II) Chloride; Iodine Copper(II)
as well as transesterification of esters.143 3-Methyl-2-butenyl es-
Chloride; Iodine Nitrogen Tetroxide; Iodine Potassium Iodate;
ters are converted to the carboxylic acid and alcohol precursors
Iodine Silver Acetate; Iodine Silver Benzoate; Iodine Silver(I)
with I2 at ambient temperatures, although simple allylic esters
Fluoride; Iodine Silver Trifluoroacetate; Lead(IV) Acetate
do not react.144 Prenyl ethers can be cleaved to the correspond-
Iodine; Mercury(II) Oxide Iodine; Thallium(I) Acetate Iodine;
ing alcohol in the presence of I2,145 as are trityl ethers with
Triphenylphosphine Iodine.
I2 in methanol.146 In a similar manner, prenyl carbamates are
deprotected to regenerate the original amine compound.147 p-
Methoxybenzyl ethers are cleaved with I2 in methanol, but sim-
ple benzyl ethers are not.148 Alkyl tert-butyldimethylsilyl ethers
1. Field, K. W.; Wilder, D.; Utz, A.; Kolb, K. E., J. Chem. Educ. 1987,
are selectively cleaved in the presence of the analogous aryl silyl
64, 269.
ether by I2 in methanol.149 Iodine is used under microwave ir-
2. Heasley, V. L.; Shellhamer, D. F.; Heasley, L. E.; Yeager, D. B.; Heasley,
radiation to facilitate the reaction of 1,2-diols with dihydropyran
G. E., J. Org. Chem. 1980, 45, 4649.
to give the monotetrahydropyranyl ether.150 Iodine catalyzes the
3. (a) Klein, J., J. Am. Chem. Soc. 1959, 81, 3611. (b) van Tamelen, E.
formation of tetrahydropyranyl ethers from alcohols, as well as
E.; Shamma, M., J. Am. Chem. Soc. 1954, 76, 2315. (c) House, H. O.;
the conversion (in methanol) to the original alcohol.151 Oximes
Carlson, R. G.; Babad, H., J. Org. Chem. 1963, 28, 3359. (d) Corey, E.
are converted back to the carbonyl precursor by heating with I2 in
J.; Albonico, S. M.; Koelliker, U.; Schaaf, T. K.; Varma, R. K., J. Am.
acetonitrile.152
Chem. Soc. 1971, 93, 1491. (e) Dowle, M. D.; Davies, D. I., Chem. Soc.
Rev. 1979, 8, 171. (f) Cardillo, G.; Orena, M., Tetrahedron 1990, 46,
3321.
Miscellaneous Reactions. Iodine is an oxidizing agent under
the proper conditons. Iodine, in conjunction with DMSO and hy- 4. Knapp, S.; Rodriques, K. E.; Levorse, A. T.; Ornaf, R. M., Tetrahedron
Lett. 1985, 26, 1803.
drazine monohydrate in aqueous acetonitrile, efficiently oxidized
5. Wadsworth, D. H.; Detty, M. R.; Murray, B. J.; Weidner, C. H.; Haley,
secondary alcohols to the corresponding ketone.153 Photochem-
N. F., J. Org. Chem. 1984, 49, 2676.
ical oxidative cleavage of styrenes gave carboxylic acids upon
6. Freiberg, L. A., J. Am. Chem. Soc. 1967, 89, 5297.
treatment with mesoporous silica FSM-16 iodine.154 Aldehydes
were produced from allylic and benzylic alcohols under simi- 7. Renaud, P.; Fox, M. A., J. Org. Chem. 1988, 53, 3745.
lar conditions.155 Iodine and NH4OH converted aldehydes into 8. Kirk, K. L., J. Org. Chem. 1978, 43, 4381.
A list of General Abbreviations appears on the front Endpapers
IODINE 11
9. (a) Brown, H. C.; Rathke, M. W.; Rogić, M. M.; DeLue, N. R., 37. Ogata, Y.; Watanabe, S., J. Org. Chem. 1980, 45, 2831.
Tetrahedron 1988, 44, 2751. (b) DeLue, N. R.; Brown, H. C., Synthesis
38. (a) Hell, C., Chem. Ber. 1881, 14, 891. (b) Volhard, J., Liebigs Ann.
1976, 114.
Chem. 1887, 242, 141. (c) Zelinsky, N., Chem. Ber. 1887, 20, 2026.
10. (a) Zweifel, G.; Fisher, R. P.; Snow, J. T.; Whitney, C. C., J. Am. Chem. (d) Watson, H. B., C. R. Hebd. Seances Acad. Sci., Ser. C 1930, 7, 180.
Soc. 1972, 94, 6560. (b) Zweifel, G.; Arzoumanian, H.; Whitney, C. C.,
39. Bunce, N. J., J. Org. Chem. 1972, 37, 664.
J. Am. Chem. Soc. 1967, 89, 3652.
40. (a) Hunsdiecker, H.; Hunsdiecker, C., Chem. Ber. 1942, 75, 291.
11. Dittrich, S., J. Chromatogr. 1967, 31, 628.
(b) Borodine, A., Justus Liebigs Ann. Chem. 1861, 119, 121.
12. Kirk-Othmer Encyclopedia of Chemical Technology, 3rd ed.; Wiley: (c) Johnson, R. G.; Ingham, R. K., C. R. Hebd. Seances Acad.
New York, 1978; Vol. 13, p 649 (see p 652).
Sci., Ser. C 1956, 56, 219. (d) Wilson, C. V., Org. React. 1957, 9,
341.
13. Schmeisser, M. In Handbook of Preparative Inorganic Chemistry, 2nd
ed.; Brauer, G., Ed.; Academic: New York, 1963; Vol. 1, p 277.
41. Saulnier, M. G.; Gribble, G. W., J. Org. Chem. 1982, 47, 757.
14. Reference 12, p 655.
42. Gribble, G. W.; Saulnier, M. G., Tetrahedron Lett. 1980, 21, 4137.
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R. E.; Smith, R. P.; Hodge, H. C., Eds.; Williams and Wilkins:
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Baltimore, 1984; Section III, p 213. (b) Reference 12, p 657,
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659.
46. (a) Doering, W. v E. In Theoretical Organic Chemistry, the Kekule
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18. Brown, W.; Turner, A. B., J. Chromatogr. 1967, 26, 518.
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