Detection of Aryl Radicals in Hydrodediazoniations

Article abstract of DOI:10.1021/jo962128y

Iodoacetic acid, an effective aryl radical trapping agent, was employed to investigate the reactive intermediates in several hydrodediazoniations. Isolation of an aryl iodide constitutes a positive result in the test for aryl radicals. Equally as important is the lower yield of the reduction product when the trap diverts radicals from their usual reaction path. Hydrodediazoniations performed in MeOH, EtOH, i-PrOH, benzyl alcohol, THF, tetramethylurea, formamide, and hypophosphorous acid all involve aryl radical intermediates. Ferrocene was found to be an effective initiator in most of these reactions; through its action as an electron donor, it serves to shorten reaction times and to improve yields of hydrodediazoniation products. All hydrodediazoniations examined, whether initiated or not, involve radical intermediates.

Full text of DOI:10.1021/jo962128y

8304
J . Org. Chem. 1997, 62, 8304-8308
Detection of Ar yl Ra d ica ls in Hyd r od ed ia zon ia tion s†
Frederick W. Wassmundt* and William F. Kiesman‡
Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-4060
Received November 13, 1996 (Revised Manuscript Received September 9, 1997X)
Iodoacetic acid, an effective aryl radical trapping agent, was employed to investigate the reactive
intermediates in several hydrodediazoniations. Isolation of an aryl iodide constitutes a positive
result in the test for aryl radicals. Equally as important is the lower yield of the reduction product
when the trap diverts radicals from their usual reaction path. Hydrodediazoniations performed in
MeOH, EtOH, i-PrOH, benzyl alcohol, THF, tetramethylurea, formamide, and hypophosphorous
acid all involve aryl radical intermediates. Ferrocene was found to be an effective initiator in most
of these reactions; through its action as an electron donor, it serves to shorten reaction times and
to improve yields of hydrodediazoniation products. All hydrodediazoniations examined, whether
initiated or not, involve radical intermediates.
In tr od u ction
radical traps (eqs 1 and 2). Evidently, iodine transfer is
Many investigators have sought to determine the
mechanisms by which the diazonium group is replaced
by hydrogen from a variety of organic substances.1 In
some of the more prominent reduction methods, careful
consideration of the complex mechanistic evidence sup-
ports the intermediacy of radicals. What is lacking in
these cases is a single simple yet convincing piece of
evidence. In contrast, identification of the reactive
intermediates in less prominent hydrodediazoniation
methods has received scant attention. Unfortunately,
very few generalizations have been made about the
behavior of diazonium salts in these hydrodediazoniation
reactions. Herein, we describe the systematic application
of a simple aryl radical trap to a variety of hydrodedia-
zoniation methods.
In general, a good radical trapping agent must be
soluble, stable to the reaction conditions, inert to ionic
reactions, and easily separable from the other products
of the reaction. In addition, it should not foster the
formation of radicals or substantially alter the original
conditions of the reaction. Alkyl iodides have long been
used as traps for alkyl radicals.2 Bunnett and co-workers
first demonstrated that aryl radicals abstract iodine from
substituted iodobenzenes.3 Iodobenzoic acid4 and io-
doacetic acid5,6 have also been successfully employed as
Ar• + IC6H4CO2H f ArI + •C6H4CO2H
Ar• + ICH2CO2H f ArI + •CH2CO2H
(1)
(2)
a reaction unique to radicals. Therefore, the replacement
of the diazonium group by iodine from such sources
demonstrates the presence of an aryl radical. For our
investigations iodoacetic acid served as the iodine source.7
The use of this functionalized trapping agent simplified
the analysis of the product, because any surplus agent
could be removed easily by washing with base.
Isolation of an aryl iodide from the reaction mixture
constitutes a positive result in the primary, qualitative
test for the presence of aryl radicals. A second confirma-
tory portion of the test involves an examination of the
change in yield of the hydrodediazoniation product when
the trap is added. If the normal product is formed
through an aryl radical intermediate, then the yield of
the normal radical product must decrease as the radicals
are diverted toward aryl iodide formation. Thus a
decrease of the normal product accompanying the aryl
iodide formation confirms that the radical trap was
interrupting the product-forming step.
Resu lts a n d Discu ssion
† Part of the Ph.D. Thesis of W. F. Kiesman, University of Con-
necticut, 1995.
For the investigation of hydrodediazoniations, which
are usually performed under neutral or acidic conditions,
iodoacetic acid functioned as the trap because of its
excellent solubility in a wide range of solvents. First we
wanted to test the effect that the presence of the trap
had upon a reaction of known mechanism. The Schi-
emann reaction served as an ionic test reaction for
iodoacetic acid.8 A mixture of 2 equiv of iodoacetic acid
and 4-bromobenzenediazonium tetrafluoroborate was
boiled in CH2Cl2 for 14 days. The normal ionic product
of the Schiemann reaction (4-bromofluorobenzene) was
formed in 30% yield while no iodine transfer product (4-
bromoiodobenzene) was detected in the reaction mixture.
This simple experiment served to demonstrate that,
‡ NSF Predoctoral Fellow (1993-1995). Present address: Biogen,
Inc., 14 Cambridge Center, Cambridge, MA 02142.
X Abstract published in Advance ACS Abstracts, November 1, 1997.
(1) (a) Kornblum, N. A.; Cooper, G. D.; Taylor, J . E. J . Am. Chem.
Soc. 1950, 72, 3013. Kornblum, N. Org. React. 1944, 2, 262. (b)
Wulfman, D. S. The Chemistry of Diazonium and Diazo Groups. In
The Chemistry of the Functional Groups; Patai, S., Ed.; Wiley: New
York, 1978; pp 286-287. (c) Hegarty, A. F., ref 1b, pp 564-565. (d)
Saunders, K. H.; Allen, R. L. M. Aromatic Diazo Compounds, 3rd ed.;
Edward Arnold: London, 1985; pp 537-548. (e) Zollinger, H. Diazo
Chemistry I: Aromatic and Heteroaromatic Compounds; VCH: New
York, 1994.
(2) Walling, C. Free Radicals in Solution; Wiley: New York, 1957;
p 155, 255.
(3) Bunnett, J . F.; Wamser, C. C. J . Am. Chem. Soc. 1966, 88, 5534.
Brydon, D. L.; Cadogen, J . I. G. J . Chem. Soc. C. 1968, 819. Broxton,
T. J .; Bunnett, J . F.; Paik, C. H. J . Org. Chem. 1977, 42, 643.
(4) Wassmundt, F. W.; Kiesman, W. F. J . Org. Chem. 1995, 60, 1713.
(5) (a) Werner, R.; Ru¨chardt, C. Tetrahedron Lett. 1969, 28, 2407.
(b) Ru¨chardt, C.; Merz, E.; Freudenburg, B.; Opgenorth, H. J .; Tan, C.
C.; Werner, R. Free-radical Reactions of Aromatic Diazonium Salts.
In Essays on Free-radical Chemistry, Spec. Publ. 24; The Chemical
Society: London, 1970; pp 56-66.
(7) In unpublished work, phenylacetic acid was isolated from the
reaction mixtures of trapping experiments during the examination of
Gomberg-Bachmann arylations in benzene. This result traces the fate
of the alkyl radical generated in eq 2.
(6) Besse, J .; Zollinger, H. Helv. Chim. Acta 1981, 64, 532, 537.
(8) Swain, C. G.; Rogers, R. J . J . Am. Chem. Soc. 1975, 97, 799.
S0022-3263(96)02128-7 CCC: $14.00 © 1997 American Chemical Society

Detection of Aryl Radicals in Hydrodediazoniations
J . Org. Chem., Vol. 62, No. 24, 1997 8305
hydrogen atom source. Hodgson and Kershaw11 found
that byproducts of the abstraction of the hydrogen from
the alcohols are the carbonyl compounds. One result
confirmed their observation. We found in BnOH that
benzaldehyde was formed in 42% yield in both the
catalyzed and uncatalyzed reactions. These observations
coincide with bond strength data which show that the
weakest C-H bond in the alcohol involves the bond
between the hydrogen atom R to the oxygen (the carbinyl
hydrogen) and the carbinyl carbon. The results support
the following general free-radical mechanism.1a
Ta ble 1. P r od u cts fr om Tr a d ition a l Rea ction of
4-Br om oben zen ed ia zon iu m Tetr a flu or obor a te in
Selected Alcoh ols
products (% yield)c
reagenta
MeOH
conditionsb
BrC6H4H
BrC6H4OR
BrC6H4I
no trap
ICH2CO2H
no trap
ICH2CO2H
no trap
ICH2CO2H
no trap
46
2
70
4
61
13
54
18
20
16
4
11
0
0
0
0
49
58
64
56
EtOH
i-PrOH
BnOH
ICH2CO2H
a
The reactions were carried out with 0.37 mmol of diazonium
b
salt in 2 mL of reagent. Two equivalents of iodoacetic acid were
employed in the trapping experiments. c Yields were determined
by GC analysis versus an internal standard.
under standard conditions, iodoacetic acid did not induce
a radical reaction or interfere in any way with the normal
course of the ionic reaction of the diazonium salt.
Red u ction w ith H3P O2. A common method em-
ployed to replace a diazonium group by hydrogen uses
hypophosphorous acid both as an electron donor and as
a hydrogen atom source.1a-d,5b EPR9 and CINDP10 were
used to study the mechanism of the reaction. Beckwith
observed in the initiation stage of the reaction EPR
An important competing reaction in the more polar
MeOH and EtOH is the formation of an ether by an ionic
process (eq 7). The overall result is an increase in the
amount of the ether product simultaneous with a de-
crease in reduction in the presence of iodoacetic acid.
•-
signals which he assigned to the HPO2 species. The
extremely short lifetime of the aryl radical precludes its
direct observation by EPR. However, in the presence of
maleic acid signals were observed that were attributed
to the product of reaction of the aryl radical and maleic
acid. We thought it worthwhile to apply the iodoacetic
acid trap to this reaction to intercept aryl radicals.
Addition of iodoacetic acid to the hydrodediazoniation of
4-bromobenzenediazonium tetrafluoroborate in H3PO2
solution resulted in the formation of 4-bromoiodobenzene
in 33% yield. This result confirms the existence of aryl
radicals in the reaction and provides additional support
for Kornblum’s free-radical mechanism.1a
-N2
8 Ar+ ROH8 ArOR + H+
(7)
+
ArN2
In contrast to other diazonium salt reactions, no
obvious catalyst is employed to initiate a radical mech-
anism. Apart from operations in base, there are two
possible initiation pathways for the hydrodediazoniations
in alcohols. In one, Bunnett and Yijima12 proposed that
in MeOH a direct oxidation of the alcohol by the diazo-
nium salt occurs (eqs 8 and 9). Diazonium salts have
Hyd r od ed ia zon ia tion s in Alcoh ols. Methanol, eth-
anol, isopropyl alcohol, and benzyl alcohol (BnOH) have
all been used as reagents for hydrodediazoniations.1d
Previous investigators found that the speed of the reac-
tion is enhanced in basic methanol solutions but is
retarded in acidic or neutral conditions.3 We decided to
investigate the hydrodediazoniations of 4-bromobenzene-
diazonium tetrafluoroborate not only in methanol but in
all of the above alcohols. Under typical reaction condi-
tions the diazonium salt was added to the alcohol and
the solution boiled until the starting material was
consumed. The reactions were performed both in the
absence and presence of iodoacetic acid. The results are
shown in Table 1. Even the slowest of these reactions
was complete in about 2 h. In the absence of the trap,
the reduction product (bromobenzene) is formed in
preference to the aryl ethers in MeOH and EtOH. No
ethers could be detected in the reactions performed in
the less polar alcohols, i-PrOH and BnOH, and reduction
remained the major reaction. Upon addition of the trap,
the aryl iodide was formed and the amount of hydrod-
ediazoniation product dropped sharply. Both the primary
test and the confirmatory test indicated the presence of
radical intermediates. The alcohol is undoubtedly the
ArN2+ + HOCH3 f ArN2• + [HOCH3]•+
ArN2• f Ar• + N2
(8)
(9)
been shown to oxidize, by a direct electron transfer,
polycyclic aromatics13 and tertiary amines.5b The oxida-
tion potential of MeOH (ca. 0.8 V)14 is certainly within
the range that makes this transfer possible. Equally
reasonable is an alternative initiation. Here, joining of
the diazonium cation to the oxygen of the solvent is
followed by proton loss and homolytic bond cleavage (eq
10). What results are the diazenyl radical and an alkoxy
radical. Initiations involving this linkage-homolysis
pathway in diazonium salt reactions have been postu-
lated before.15 A diazoether intermediate has been
proposed in the reaction between alkyl nitrites and
(11) Hodgson, H. H.; Kershaw, A. J . Chem. Soc. 1930, 2784.
(12) Bunnett, J . F.; Yijima, C. J . Org. Chem. 1977, 42, 639.
(13) Andersen, M. L.; Handoo, K. L.; Parker, V. D. Acta Chem.
Scand. 1991, 45, 983.
(14) Bagotzky, V. S.; Vasilyev, Y. B. Electrochim. Acta 1964, 9, 869.
(15) Tro¨ndlin, F.; Ru¨chardt, C. Chem. Ber. 1977, 110, 2494.
(9) Beckwith, A. L. J . Aust. J . Chem. 1972, 25, 1887.
(10) Levit, A. F.; Kiprianova, L. A.; Gragerov, I. P. Zh. Org. Khim.
1975, 11, 2351; Chem. Abstr. 1975, 84, 42954d.

8306 J . Org. Chem., Vol. 62, No. 24, 1997
Wassmundt and Kiesman
Ta ble 3. P r od u cts fr om Rea ction s of
Ta ble 2. P r od u cts fr om F er r ocen e-P r om oted Rea ction s
of 4-Br om oben zen ed ia zon iu m Tetr a flu or obor a te in
Selected Alcoh ols
4-Br om oben zen ed ia zon iu m Tetr a flu or obor a te in THF
products (% yield)c
products (% yield)c
catalyst
conditionsa,b
BrC6H4H
BrC6H4I
reagenta
MeOH
conditionsb
BrC6H4H
BrC6H4OR
BrC6H4I
none
none
no trap
ICH2CO2H
no trap
65
20
68
21
no trap
ICH2CO2H
no trap
ICH2CO2H
no trap
ICH2CO2H
no trap
65
3
82
8
82
10
67
18
0
0
0
0
0
0
0
0
41
55
72
72
81
57
ferrocene
ferrocene
EtOH
ICH2CO2H
a
The reactions were carried out with 0.37 mmol of diazonium
i-PrOH
BnOH
b
salt in 2 mL of THF. Two equivalents of iodoacetic acid were
employed in the trapping experiments. c Yields were determined
by GC analysis versus an internal standard.
ICH2CO2H
a
Interestingly, in the presence of iodoacetic acid, the
yields of reduction product in the catalyzed reactions are
almost identical with those found for the reactions
performed in the absence of a promoter (Table 1). The
use of a promoter speeds the radical reaction to the point
where competing ionic reactions become negligible, and
ether formation is thereby suppressed. In addition,
benzaldehyde is a byproduct of the ferrocene promoted
reactions performed in BnOH. This result mirrors that
obtained in the reactions performed in the absence of a
promoter.
The reactions were carried out with 0.37 mmol of diazonium
b
salt in 2 mL of reagent. Two equivalents of iodoacetic acid were
employed in the trapping experiments. c Yields were determined
by GC analysis versus an internal standard.
arylamines and was thought to undergo homolytic bond
cleavage to form a diazenyl radical and an alkoxy radical
(eq 11).16
ArNH2 RONO8 ArN2sOR f ArN2• + •OR (11)
-H2O
THF . Hydrodediazoniations in THF share many of the
traits of the reactions performed in alcohols. Whether
the THF reductions were performed in the presence of
an initiator or not, the addition of iodoacetic acid inter-
cepted the aryl radical and interrupted the hydrogen
atom abstraction (Table 3). These results concur with
those obtained by Ru¨chardt et al. in their study of
reductions performed in 1,3-dioxolane.5 In the ferrocene-
initiated reactions, the reaction time was greatly dimin-
ished and the yields were increased. Therefore, in THF
as in the alcohols, the replacement of the diazonium
group by hydrogen is a free-radical process.19
Hyd r od ed ia zon ia t ion s in Am id es. In a previous
paper the synthetic utility and mechanisms of hydrod-
ediazoniations of diazonium salts in dimethylformamide
and dimethylacetamide were described in detail.4 The
following discussion addresses separately the mechanistic
investigations of hydrodediazoniations performed in the
related amide solvents tetramethylurea (TMU) and for-
mamide.
In itia ted Hyd r od ed ia zon ia tion s in Alcoh ols. The
preceding discussion focused solely upon hydrodediazo-
niations performed in the absence of an initiator. In
previous investigations of diazonium salt reactions we
have used soluble electron donors to initiate free-radical
reactions.4,17,18 The donor gives up an electron to the
diazonium cation (eq 12). The resulting diazenyl radical
releases nitrogen, and the reactive aryl radical interme-
diate is formed (eq 13). The radical hydrodediazoniations
in alcohols should benefit from the use of a promoter such
as ferrocene. The effectiveness of the initiator was
demonstrated by the results displayed in Table 2. In the
presence of 10 mol % of ferrocene, the reactions were
completed within 20 min, as compared with the uncata-
lyzed reactions which took several hours. This dramatic
decrease in reaction time from only a small amount of
ferrocene was attributed to more efficient initiation.
ArN2+ + Fc f ArN2• + Fc+
ArN2• f Ar• + N2
(12)
(13)
Tetr a m eth ylu r ea . Rutherford and Redmond20 found
that hydrodediazoniations could be performed in TMU
and noted that the reactivity of the diazonium salts in
this medium parallels that seen in EtOH and THF.
Several years earlier DeTar21 and Meerwein22 had pro-
posed that the latter reductions resulted from hydride
abstraction by aryl cation intermediates. From the
observed similarity, Rutherford and Redmond suggested
that the reaction in TMU also followed an ionic pathway.
They attempted to support this mechanistic choice by the
Addition of the ferrocene also increased the yields of
the reduction products as a comparison of the yields in
Table 2 with those in Table 1 shows. Furthermore,
ferrocene, in the cases of MeOH and EtOH, suppressed
the formation of the aryl ether products entirely. Clearly
our introduction of an electron donor improved the
efficiency of the radical hydrodediazoniation reactions.
These improved reactions also warrant mechanistic
investigation. Upon the addition of the trap to the
promoted reactions, the aryl iodide was formed and the
yield of the reduction product dropped. Similar to the
results of the uncatalyzed reactions, the primary and
confirmatory tests both demonstrate that the ferrocene-
initated reaction follows a radical pathway.
-
unsubstantiated assertion that the PF6 counterion
would not survive in a free-radical reaction. We and
others1a,19 have demonstrated that hydrodediazoniations
in alcohols and THF follow radical pathways. Hence, this
reaction is an attractive candidate for our radical test.
(19) The product-forming and chain-propagating steps of the hy-
drodediazoniations in THF are best accommodated by the mechanism
described in Cadogan, J . I. G.; Molina, G. A. J . Chem. Soc., Perkin
Trans. 1 1973, 541.
(16) Doyle, M. P.; Dellaria, J . F.; Siegfried, B.; Bishop, S. W. J . Org.
Chem. 1977, 42, 3494.
(17) Pedemonte, R. P. Ph.D. Dissertation, University of Connecticut,
(20) Rutherford, K. G.; Redmond, W. A. J . Org. Chem. 1963, 28,
568.
1991. Wassmundt, F. W.; Pedemonte, R. P. J . Org. Chem. 1995, 60,
(21) DeTar, D. F.; Kosuge, T. J . Am. Chem. Soc. 1958, 80, 6072.
(22) Meerwein, H.; Allendo¨rfer, H.; Beekmann, P; Kunert, F.;
Morschel, H.; Pawellek, F.; Wunderlich, K. Angew. Chem. 1958, 70,
211.
4991.
(18) Wassmundt, F. W.; Kiesman, W. F. J . Org. Chem. 1995, 60,
196.

Detection of Aryl Radicals in Hydrodediazoniations
J . Org. Chem., Vol. 62, No. 24, 1997 8307
Sch em e 2
F igu r e 1.
Sch em e 1
hydrogen from formamide by hydroxyl radicals it was
found that the hydrogen abstraction occurs solely from
the formyl position.24 The aryl radical in a similar
manner attacks the weakest bond in formamide, the
formyl C-H bond. We propose the free-radical mecha-
nism displayed in Scheme 2 for the hydrodediazoniation
in formamide.
The hydrodediazoniations in the amide family of
reagents share a number of common features. The most
likely initiation for the radical reaction in amide solvents
is through a linkage-homolysis pathway discussed in our
earlier paper.4 The solvent is the hydrogen source. In
TMU and DMA, the hydrogen comes from the N-methyl
position. In DMF, the hydrogen abstraction takes place
at both the N-methyl and formyl positions, and in
formamide the formyl position is the sole hydrogen atom
source.
The hydrodediazoniation of 4-bromobenzenediazonium
tetrafluoroborate in TMU was performed in the presence
and absence of iodoacetic acid. The fluoroborate salt was
substituted for the hexafluorophosphate for convenience.
In the absence of the trap, bromobenzene was produced
in 63% yield. Upon addition of the iodoacetic acid, the
yield of bromobenzene dropped to 23% while the aryl
iodide (53%) became the major product. In addition, in
the presence of 10 mol % of ferrocene, the aryl iodide was
formed in 65% yield while the yield of bromobenzene fell
to 20%. Similar to other radical hydrodediazoniations,
the formation of the aryl iodide clearly demonstrated the
presence of aryl radicals in this reaction. Hydrodedia-
zoniations in TMU are like those performed in DMF and
DMA,4 and our results support the following general free-
radical chain mechanism (Scheme 1).
F or m a m id e. In yet another hydrodediazoniation
reaction, diazonium fluoroborates were converted into the
corresponding hydrocarbons in moderate to good yields
in a mixture of Et3N and formamide.23 Threadgill and
Gledhill showed in an elegant labeling experiment that
the sole source of hydrogen was that of the formyl
position of formamide. The authors discounted the
possibility of a radical pathway because no biphenyl
derivatives could be detected in the reaction mixture;
instead, they proposed that an intramolecular hydride
transfer displaces nitrogen from an intermediate triazene
derivative in a cyclic transformation (Figure 1). We felt
our test could be used to advantage in the elucidation of
the mechanism of this reaction.
Con clu sion s
Careful review of the literature pertaining to hydrod-
ediazoniations reveals that aryl radicals have often been
proposed as intermediates in these reactions but this
view has not gained full acceptance. The primary test
employed iodoacetic acid as an aryl radical trap, and our
results are consistent with the presence of aryl radicals
in these reactions. The intermediacy of an aryl radical
in the product-forming step was established by the fact
that the yield of the intended product decreased in the
presence of the trap which diverts the intermediate
toward aryl iodide formation. Importantly, all hydrod-
ediazoniation methods examined, whether or not a
promoter was present, involve radical intermediates.
Exp er im en ta l Section
Gen er a l. Diazonium salts were made and purified by
methods previously described.4 All liquids were reagent grade
and were used as purchased. Melting points are uncorrected.
When 4-bromobenzenediazonium fluoroborate was dis-
solved in formamide, gas evolution was spontaneous. The
reaction was completed within 10 min and yielded 66%
of the hydrogen replacement product. The transforma-
tion was achieved in the absence of Et3N. Clearly Et3N
was not needed for the reaction. We chose to omit Et3N
for simplicity and to remove all ambiguity concerning the
substance causing reduction. Meerwein and co-workers,
for example, identify tertiary amines as reductants.22
Upon addition of iodoacetic acid, the aryl iodide was
formed in 56% yield while the yield of the reduction
product dropped to 8%. The results of the primary and
confirmatory tests demonstrate the presence of aryl
radicals and deny the validity of the cyclic intermediate.
Similarly, in the presence of 10 mol % of ferrocene, the
aryl iodide was formed in 58% yield while the yield of
bromobenzene fell to 11%. The site of hydrogen abstrac-
tion from formamide is also consistent with a free-radical
reaction. For example, in a study of the abstraction of
Sch iem a n n Rea ction w ith Iod oa cetic Acid a s a Tr a p .
4-Bromobenzenediazonium tetrafluoroborate (0.100 g, 0.370
mmol) and iodoacetic acid (0.138 g, 0.740 mmol) were dissolved
in 10 mL of CH2Cl2. The solution was placed on a steam bath
and heated under reflux for 14 days. GC analysis showed that
the reaction mixture contained 1-bromo-4-fluorobenzene pro-
duced in 30% yield and 1-bromo-4-chlorobenzene in 5% yield,
the latter substance presumably formed by Swain’s ionic
mechanism.8 No 1-bromo-4-iodobenzene was detected.
Hyd r od ed ia zon ia tion Usin g Hyp op h osp h or ou s Acid .25
H3PO2 (1.47 g, 11.1 mmol) and iodoacetic acid (0.275 g, 1.48
mmol) were dissolved in 5 mL of water and chilled in an ice-
water bath. Solid 4-bromobenzenediazonium tetrafluoroborate
(0.200 g, 0.740 mmol) was added gradually with stirring to
the chilled solution. The reaction mixture was kept between
5 and 10 °C for 3 h, allowed to warm to rt, and then stirred
(24) Hayon, E.; Ibata, T.; Lichtin, N. N.; Simic, M. J . Am. Chem.
Soc. 1970, 92, 2, 3898.
(25) (a) Kochi, J . K. J . Am. Chem. Soc. 1957, 79, 2942. (b)
Dickerman, S. C.; Weiss, K.; Ingberman, A. K. J . Am. Chem. Soc. 1958,
80, 1904. (c) Dickerman, S. C.; DeSouza, D. J .; J acobson, N. J . Org.
Chem. 1969, 34, 710. (d) Galli, C. J . Chem. Soc., Perkin Trans. 2 1981,
1459. (e) Galli, C. J . Chem. Soc., Perkin Trans. 2 1982, 1139.
(23) Threadgill, M. D.; Gledhill, A. P. J . Chem. Soc., Perkin Trans.
1 1986, 873.

8308 J . Org. Chem., Vol. 62, No. 24, 1997
Wassmundt and Kiesman
overnight. 4-Bromoiodobenzene (0.070 g, 33%) was isolated
by suction filtration.
amounts of bromobenzene and 1-bromo-4-iodobenzene. The
reported yields are the average of at least two determinations.
Tr appin g Exper im en ts: Hydr odediazon iation s in Var i-
ou s Solven ts w ith Iod oa cetic Acid a s a Tr a p . Iodoacetic
acid (0.138 g, 0.740 mmol) was dissolved in 2 mL of solvent in
a 5-mL flask equipped with a magnetic stirrer and a reflux
condenser. Solid 4-bromobenzenediazonium tetrafluoroborate
(0.100 g, 0.370 mmol) was added gradually with stirring. The
reaction mixture effervesced immediately. After being heated
on a steam bath for 10 min, the reaction mixture was allowed
to cool to rt and poured into 30 mL of Et2O. The ether solution
was extracted with three 10-mL portions of 10% KOH and
dried with MgSO4. GC analysis showed that bromobenzene
and 1-bromo-4-iodobenzene were produced in 22.9% and 53.3%
yields, respectively.
In formamide, under similar conditions, 1-bromo-4-iodoben-
zene was the isolated solid product.
Tr a p p in g Exp er im en ts: Gen er a l P r oced u r e for F er -
r ocen e-In itia ted Hyd r od ed ia zon ia tion s in Va r iou s Sol-
ven ts. Iodoacetic acid (0.138 g, 0.740 mmol) and ferrocene
(0.007 g, 0.037 mmol) were dissolved in 2 mL of solvent in a
5-mL flask equipped with a magnetic stirrer and a reflux
condenser. Solid 4-bromobenzenediazonium tetrafluoroborate
(0.100 g, 0.370 mmol) was added to the catalyst solution
gradually with stirring. The reaction mixture turned blue and
effervesced immediately. After being heated on a steam bath
for 10 min, the reaction mixture was allowed to cool to rt and
poured into 30 mL of Et2O. The ether solution was extracted
with three 10-mL portions of 10% KOH, dried with MgSO4,
and analyzed by GC. Results for various alcohols are pre-
sented in Table 2.
P r od u ct An a lysis. Products were identified by comparison
of retention times with authentic samples. Naphthalene was
added, after workup, as an internal quantitative standard.
Yields were calculated, based upon the response factors found
for equimolar amounts of naphthalene standard vs known
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