Halo- and azidodediazoniation of arenediazonium tetrafluoroborates with trimethylsilyl halides and trimethylsilyl azide and Sandmeyer-type bromodediazoniation with Cu(I)Br in [BMIM][PF6] ionic liquid

Article abstract of DOI:10.1021/jo701937e

(Chemical Equation Presented) Reaction of [ArN₂][BF₄] salts immobilized in [BMIM][PF₆] ionic liquid (IL) with TMSX (X = I, Br) and TMSN₃ represents an efficient method for the preparation of iodo-, bromo-, and azido-derivatives via dediazoniation. The reactions can also be effected starting with ArNH₂ by in situ diazotization with [NO][BF₄] followed by reaction with TMSX or TMSN₃. Depending on the substituents on the benzenediazonium cation, competing fluorodediazoniation (ArF formation) and hydrodediazoniation (ArH formation) were observed. Dediazoniation with TMSN₃ and with TMSI generally gave the highest chemoselectivity toward ArN₃ and ArI formation. The IL was recycled and reused up to 5 times with no appreciable decrease in the conversions. Multinuclear NMR monitoring of the interaction of [ArN ₂][BF₄]/TMSX, [BMIM][PF₆]/TMSX, and [BMIM][PF₆]/TMSX/[ArN₂][BF₄] indicated that TMSF is formed primarily via [ArN₂][BF₄]/ TMSX, generating [ArN₂][X] in situ, which gives ArX on dediazoniation. Competing formation of ArF in Sandmeyer-type bromodediazoniation of [ArN ₂][BF₄] with Cu(I)Br immobilized in the IL points to significant involvement of heterolytic dediazoniation.

Full text of DOI:10.1021/jo701937e

dediazoniation of ArN2+ salts have been extensively studied.1-6
The heterolytic versus homolytic pathways are greatly influenced
by the nature of solvent/nucleophile and substituent(s) on the
diazonium cation.1,4 Heterolytic dediazoniation dominates in low
nucleophilicity/highly ionizing solvents, in protic superacids or
in aqueous acids, and with electron-donating substitutents,
whereas homolysis is promoted in more nucleophilic solvents,
and in the presence of electron-withdrawing substitutes that
increase the electron-demand at Nâ.1,2 For thermal dediazonia-
tion of R-C6H4-N2+ BF4-, whereas formation of Ar-Nu and
ArF is indicative of a heterolytic process (Ar+ formation and
trapping), the presence of ArH (hydrodediazoniation) implies
intervention by a homolytic pathway.1
Halo- and Azidodediazoniation of
Arenediazonium Tetrafluoroborates with
Trimethylsilyl Halides and Trimethylsilyl Azide
and Sandmeyer-Type Bromodediazoniation with
Cu(I)Br in [BMIM][PF6] Ionic Liquid§
Abigail Hubbard, Takao Okazaki, and Kenneth K. Laali*
Department of Chemistry, Kent State UniVersity,
Kent, Ohio 44242
klaali@kent.edu
We had earlier shown that various R-C6H4-N2+ BF4- salts
are immobilized in imidazolium ILs and upon thermal dedia-
zoniation produce the corresponding ArF in high yields.7 In
continuation of our studies focusing on onium ion chemistry
and electrophilic aromatic substitution in ILs,7-13 we report on
ReceiVed September 10, 2007
-
dediazoniation of R-C6H4-N2+ BF4 salts in [BMIM][PF6]
(Formula 1) in the presence of TMSX (TMS ) trimethylsilyl;
X ) Cl, Br, I) and TMSN3 as convenient, easy to perform,
economical processes to prepare R-C6H4-Br, R-C6H4-I, and
R-C6H4-N3 in one pot, with easy workup and recycling of
the IL. The reactions could also be carried out starting with the
anilines, by generating the diazonium salts in situ. Interactions
of TMSI and TMSN3 with [PhN2][BF4] and with [BMIM][PF6]
were directly monitored by multinuclear NMR. Immobilization
of Cu(I)Br in [BMIM][PF6]14 enabled the IL version of the
classical Sandmeyer bromodediazoniation14 to be examined.
Keumi et al.15 reported some years ago that dediazoniation
of 2-fluorenediazonium tetrafluoroborate in DMF-THF mixed
Reaction of [ArN2][BF4] salts immobilized in [BMIM][PF6]
ionic liquid (IL) with TMSX (X ) I, Br) and TMSN3
represents an efficient method for the preparation of iodo-,
bromo-, and azido-derivatives via dediazoniation. The reac-
tions can also be effected starting with ArNH2 by in situ
diazotization with [NO][BF4] followed by reaction with
TMSX or TMSN3. Depending on the substituents on the
benzenediazonium cation, competing fluorodediazoniation
(ArF formation) and hydrodediazoniation (ArH formation)
were observed. Dediazoniation with TMSN3 and with TMSI
generally gave the highest chemoselectivity toward ArN3 and
ArI formation. The IL was recycled and reused up to 5 times
with no appreciable decrease in the conversions. Multinuclear
NMR monitoring of the interaction of [ArN2][BF4]/TMSX,
[BMIM][PF6]/TMSX, and [BMIM][PF6]/TMSX/[ArN2][BF4]
indicated that TMSF is formed primarily via [ArN2][BF4]/
TMSX, generating [ArN2][X] in situ, which gives ArX on
dediazoniation. Competing formation of ArF in Sandmeyer-
type bromodediazoniation of [ArN2][BF4] with Cu(I)Br
immobilized in the IL points to significant involvement of
heterolytic dediazoniation.
(1) (a) Zollinger, H. Diazo Chemistry I; VCH: Weinheim, Germany,
1994; Chapter 8. (b) Zollinger, H. Diazo Chemistry I; VCH: Weinheim,
1994; Chapter 10.
(2) Olah, G. A.; Laali K. K.; Wang, Q.; Prakash, G. K. S. Onium Ions;
Wiley: New York, 1998; Chapter 2.
(3) (a) Zollinger, H. Angew. Chem., Int. Ed. 1978, 17, 141-150. (b)
Zollinger, H. Acc. Chem. Res. 1973, 6, 335.
(4) (a) Szele, I.; Zollinger, H. J. Am. Chem. Soc. 1978, 100, 2811-
2815. (b) Hashida, Y.; Landells, R. G. M.; Lewis, G. E.; Szele, I.; Zollinger,
H. J. Am. Chem. Soc. 1978, 100, 2816-2823. (c) Laali, K.; Szele, I.;
Zollinger, H. HelV. Chim. Acta 1983, 66, 1737-1747.
(5) Ambrose, H. B.; Kemp, T. J. Chem. Soc. ReV. 1979, 8, 353-365.
(6) Ussing, B. R.; Singleton, D. A. J. Am. Chem. Soc. 2005, 127, 2888-
2899.
(7) Laali, K. K.; Gettwert, V. J. J. Fluorine Chem. 2001, 107, 31-34.
(8) Laali, K. K.; Gettwert, V. J. J. Org. Chem. 2001, 66, 35-40.
(9) Laali, K. K.; Borodkin, G. I. J. Chem. Soc., Perkin Trans. 2 2002,
953-957.
(10) Sarca, V. D.; Laali, K. K. Green Chem. 2004, 6, 245-248.
(11) Laali, K. K.; Sarca, V. D.; Okazaki, T.; Brock, A.; Der, P. Org.
Biomol. Chem. 2005, 3, 1034-1042.
+
The remarkable leaving group ability of -N2 enables two
high-energy reactive intermediates namely aryl cation and aryl
radical to be generated via heterolytic and homolytic dediazo-
niation processes, respectively. The mechanistic aspects of
(12) Sarca, V. D.; Laali, K. K. Green Chem. 2006, 8, 615-620.
(13) Laali, K. K. In Ionic Liquids in Organic Synthesis; ACS Symp.
Ser. 950; Malhotra, S. V., Ed.; American Chemical Society: Washington,
DC, 2006; Chapter 2.
(14) Yadov, J. S.; Reddy, B. V. S.; Naveenkumar, V.; Rao, R. S.;
Nagaiah, K. New J. Chem. 2004, 28, 335-337.
(15) Keumi, T.; Umeda, T.; Inoue, Y.; Kitajima, H. Bull. Chem. Soc.
Jpn. 1989, 62, 89-95.
* Address correspondence to this author. Fax: 330-6723816. Phone: 330-
6722988.
§ Part of the undergraduate honors thesis of Abigail Hubbard. Halogen
Introduction Strategies through Onium Ion Chemistry in Ionic Liquid Solvents,
Kent State University, May 2007.
10.1021/jo701937e CCC: $40.75 © 2008 American Chemical Society
Published on Web 12/08/2007
316
J. Org. Chem. 2008, 73, 316-319

TABLE 1. Product Distribution in Dediazoniation Reactions in the
Presence of TMSI
FIGURE 1. Arenediazonium tetrafluoroborate salts studied.
solvent in the presence of TMSCl led to hydrodediazoniation
forming fluorene, but in DMF (or DMA) as solvent, 2-halof-
luorenes were formed. Several other arenediazonium compounds
were also studied in these solvents. Halodediazoniation ef-
ficiency increased in the order TMSCl < TMSBr < TMSI ≈
TMSN3. Addition of MeI, NBS, or NCS increased the halod-
ediazoniation conversions at the expense of protodediazoniation.
The efficacy of TMSX and TMSN3-induced dediazoniations
would be greatly enhanced if the reactions could be carried out
without resorting to volatile/hazardous organic solvents (such
as those used in ref 15), and provided they could be applied to
readily available/widely employed diazonium salts. These
considerations formed the basis for the present survey study in
which diazonium salts (1-8) shown in Figure 1 were used.
Halodediazoniation with TMSX in [BMIM][PF6]. Diazo-
nium salts listed in Figure 1 can be immobilized in [BMIM]-
[PF6] by mixing and/or by sonication. In line with an earlier
study of Keumi et al.,15 the TMSCl-induced chlorodediazonia-
tions were found to be inefficient, giving low yields of the
chloroarenes. Chemoselectivity toward halodediazonation in-
creased in going to TMSBr. Table S1 (Supporting Information)
summarizes the bromodediazoniation outcomes. Reactions were
performed at rt and at 55 °C, with the former giving generally
better results. Except for 4 (R ) H) and 1 (R ) p-t-Bu) for
which ArF, “Schiemann product”,1,7 formation was dominant,
other diazonium salts gave the bromoarenes in the 70-90%
yield range. In the case of 8 (R ) 2,4,6-Me3), selectivity toward
ArBr formation was significantly higher in the rt dediazoniation.
With 2 (p-Cl), 5 (p-Br), 7 (m-NO2), 1 (p-t-Bu), and 3 (p-Me),
the corresponding ArH compounds were also observed. How-
ever, the extent of hydrodediazoniation products formed via 1
and 3 was quite minor.
Table 1 summarizes the results of iododediazoniations with
TMSI. For comparison, the reactions were run at rt and at
65 °C. Iodoarenes were formed in high yields (85-100%). With
8, ArF and ArH were predominant. In other cases, these side
products either were not detected or were present only in minor
amounts.
A summary of the results of azidodediazoniations is presented
in Table 2. For comparison, the reactions were performed at rt
and at 65 °C. It can be seen that aryl azides were formed in
high yields and high chemoselectivity in every entry. For 8,
the yield of mesityl azide was noticeably higher in the thermal
reaction relative to that at rt. The ArF and ArH products were
either absent or formed in small amounts. It should be noted
that recycled/reused IL was used in numerous cases throughout
this study, with only small changes in the conversions (less than
5%) being observed among reactions carried out in fresh IL
versus those that utilized reused IL. In separate control studies
a Products confirmed by GC coinjection with authentic samples, GC-
MS, or by 1H NMR. b Yields determined by GC (traces of unidentified
materials were detectable by GC in some cases). c No literature data are
available under classical/conventional conditions (without IL) for compari-
son.
it was established (by GC analysis) that for a given reaction,
the fresh IL could be reused for up to five runs with no
noticeable decrease in the conversions. Table S2 (Supporting
Information) provides a summary of the product distribution
results for in situ diazotization/iododediazoniation in representa-
tive cases. Slightly lower overall conversions were achieved in
these two-step reactions as compared to the direct dediazonia-
tions, but chemoselectivity continued to remain high (with ArF
and ArH products remaining low). Minor amounts of the
unreacted anilines were present (8% for p-t-Bu, 4% for p-Me,
19% for p-Br, and <1% for p-CH3O).
Dediazoniation with Cu(I)Br in [BMIM][PF6. The Sand-
meyer reaction is a classical transformation for converting
arylamine to aryl halides. Over the years, the mechanistic aspects
of the Sandmeyer reaction have been extensively studied, and
the topic has been critically reviewed and summarized by
Zollinger.1b Involvement of the aryl radicals via homolytic
dedidazoniation was established by kinetic studies and by
product analysis. The copper salt functions as both electron-
transfer agent and ligand-transfer oxidant. In some instances
hydrodediazoniation accompanies halodediazioniation.1b
Table S3 (Supporting Information) provides a summary of
dediazoniations of the diazonium salts listed in Figure 1, in the
presence of Cu(I)Br immobilized in [BMIM][PF6]. Product
analysis is indicative of heterolytic and homolytic dediazoniation
pathways to variable degrees, depending on the substituents.
With electron-donating substituents (p-Me, p-t-Bu, 2,4,6-trim-
J. Org. Chem, Vol. 73, No. 1, 2008 317

TABLE 2. Product Distribution in Dediazoniation Reactions in the
Presence of TMSN3
Addition of TMSI to the IL at rt rapidly resulted in the
formation of TMSF, with no TMSI remaining after a few
minutes. The H NMR (Figure S1, Supporting Information)
1
shows the peaks for the IL and TMSF (no TMSI present). The
same information could be deduced via 13C NMR (Figure S2,
Supporting Information). The 19F NMR (Figure S3, Supporting
Information) exhibits the signals for [PF6] and TMSF. By
contrast, no reaction occurred when TMSN3 was added to the
IL. The 13C NMR (Figure S4, Supporting Information) shows
peaks for the IL and the unreacted TMSN3 (and the added TMS).
This was verified via 29Si NMR (Figure S5, Supporting
Information), showing TMSN3 and TMS.
When [PhN2][BF4] is immobilized in excess IL in the NMR
tube, only resonances due to the IL and the diazonium cation
are observed [13C NMR spectrum (Figure S6, Supporting
1
Information); H NMR (Figure S7, Supporting Information),
19F NMR (Figure S8, Supporting Information)]. The control
experiment to monitor the interaction between [PhN2][BF4] and
TMSN3 had to be performed under heterogeneous conditions
1
in CDCl3 due to low solubility of the diazonium salt. The H
NMR (Figure S9, Supporting Information) showed the formation
of TMSF, which was also verified via the 29Si NMR spectrum
(Figure S10, Supporting Information). The data pointed to eq 1
as the primary source of TMSF.
[PhN2][BF4] + TMSN3 f TMSF + [PhN2][N3] + BF3 (1)
Focusing on the ternary systems, upon addition of excess
TMSI to the diazonium salt immobilized in the IL, TMSF was
quickly formed and dediazoniation ensued. Signals due to PhI
began to appear at the expense of the diazonium salt (NMR
spectra: Figure S11, Supporting Information, 1H NMR; Figure
S12, Supporting Information, 13C NMR; Figure S13, Supporting
Information, 19F NMR). Figure S14 (Supporting Information)
is the 29Si NMR for the [PhN2+][BF4-]/TMSN3/[BMIM][PF6]
in CDCl3 (under heterogeneous conditions) showing the TMSF
and unreacted TMSN3.
a Products confirmed by GC coinjection with authentic samples, GC-
MS, or 1H NMR. b Yields determined by GC (traces of unidentified
materials were detectable by GC in some cases). c No literature data are
available under classical/conventional conditions (without IL) for comparison
(reaction of in situ generated [HOOCC6H5N2][Cl] with TMSN3 was reported
to give 82% of the corresponding azide: Tisler, M.; Stanovnik, B.; Zrimsek,
Z.; Kem. Drus. 1979, 26, 163-71).
ethyl, and p-OMe) the Schiemann products were predominant.
With p-Cl, hydrodediazoniation (chlorobenzene formation) and
the Schiemann product (p-bromofluorobenzene) were major.
With p-Br and m-NO2, the Sandmeyer-derived products along
with hydrodediazoniation products were formed, with no
Schiemann products being detected. The substituent effect on
product distribution can be visualized via Charts S1 and S2
(Supporting Information), showing increased formation of ArF
with electron-donating substituents and increased hydro- and
halodediazoniation with increasing electron-withdrawing power
of the substituents. Significant involvement of heterolytic
dediazonation (ArF formation) under the conditions of Sand-
meyer chemistry is noteworthy, and may stem from increased
stability of an incipient Ar+ formed via [ArN2+][BF4-] as a
tight ion pair in the IL, relative to the aryl radical.
Collectively, the control experiments suggest that whereas
in the case of TMSN3, the major source of TMSF is via eq 1,
in the case of TMSI, TMSF could be formed via both eqs 2
and 3.
[PhN2][BF4] + TMSN3 f TMSF + [PhN2][N3] + BF3 (1)
[PhN2][BF4] + TMSI f TMSF + [PhN2][I] + BF3
(2)
[BMIM][PF6] + TMSI f TMSF + [BMIM][I] + PF5 (3)
Given that the IL was used in large excess over TMSX in
halo- and azidodediazoniations, it is unlikely that eq 3 could
contribute to any significant extent to the formation of ArI, since
this would require a statistically unfavorable second metathesis
(as in eq 4), which is much more likely to produce ArF instead!
NMR Monitoring of the [ArN2+][BF4-], TMSX, and
[BMIM][PF6] Interactions. Returning to the earlier discussion
on the nature of interaction between the diazonium salt, TMSX,
and the IL, the binary systems [BMIM][PF6]/TMSI, [BMIM]-
[PF6]/TMSN3, [PhN2+][BF4-]/[BMIM][PF6], and [PhN2+][BF4-]/
TMSN3 and the ternary systems [PhN2+][BF4-]/TMSI/[BMIM]-
[PF6] and [PhN2+][BF4-]/TMSN3/[BMIM][PF6] were studied
directly by multinuclear NMR (1H, 19F, 29Si, and 13C). The
samples were studied by NMR immediately or shortly after
preparation (representative spectra in the Supporting Informa-
tion).
[ArN2][BF4] + [BMIM][PF6] (major) + [BMIM][I]
(minor) f [ArN2][I] (4)
The picture that emerges is that TMSI, TMSBr, and TMSN3
react with the diazonium tetrafluoroborates immobilized in
[BMIM][PF6] to produce TMSF, and this leads to the formation
of [ArN2][X] via metathesis, as a tight ion-pair. The latter
conveniently undergoes dediazoniation in the IL at rt (or by
mild heating) to give ArX. The TMSN3 and TMSI reactions
318 J. Org. Chem., Vol. 73, No. 1, 2008

arenediazonium salt (0.141 mmol) was added and the mixture was
stirred or sonicated until immobilized. TMSX (0.169 mmol) was
added and the reaction mixture was stirred either overnight at room
temperature or for 2 h with heat (50-60 °C for TMSBr, and 60-
70 °C for TMSI and TMSN3 reactions). Completion of the
dediazoniation reactions was indicated when N2 evolution was
ceased. The reaction mixture was extracted three times with diethyl
ether (0.5 mL × 3) to ensure complete extraction of the products
from the IL. The combined ether extract was neutralized with
sodium bicarbonate and quickly filtered prior to analysis by GC,
GC-MS, IR, or NMR. Since some of products, specially the ArF
compounds, were rather volatile, GC analyses to determine product
distribution were performed carefully, and each reaction mixture
was injected 3 times to ensure reproducibility.
(Tables 1 and 2) produced the highest chemoselectivites and
are, therefore, viable synthetic methods to prepare ArX via the
readily available [ArN2][BF4] salts, without resorting to organic
solvents like DMF and THF to perform these reactions. Product
distributions data for these reactions imply no significant
substituent effect dependency, except for 8 (due to steric effects).
Increased formation of hydrodediazoniation products (ArH) was
observed in TMSBr reactions (Table S1, Supporting Informa-
tion) with electron-withdrawing substitutents (2, 5, and 7). The
halo- and azidodediazoniations could also be carried out starting
from the corresponding amines by in situ diazotization (Table
S2, Supporting Information), with no significant substituent
effect dependency in the studies cases. The rather unique nature
of the IL as solvent for electrophilic/cationic chemistry is
manifested in attempted Cu(I)Br homolytic halodediazonation
in Sandmeyer-type reactions (Table S3, Supporting Information),
in which significant amounts of the Schiemann products were
formed, indicating notable involvement by the aryl cation.
Supporting Information Available: Tables S1-S3; experi-
mental details; plots of substituent effects on heterolytic and
homolytic dediazoniation products in the presence of Cu(I)Br
immobilized in the IL; multinuclear NMR spectra of [ArN2][BF4]/
TMSX, [BMIM][PF6]/TMSX, and [BMIM][PF6]/TMSX/[ArN2]-
[BF4] systems. This material is available free of charge via the
Internet at http://pubs.acs.org.
Experimental Section
Dediazoniation Procedure with TMSX. The Schlenk tube
equipped with a magnetic stirring bar was charged with [BMIM]-
[PF6] (3.52 mmol, 0.66 mL) under a nitrogen atmosphere. The
JO701937E
J. Org. Chem, Vol. 73, No. 1, 2008 319