Deprotection of arenediazonium tetrafluoroborate ethers with BBr 3

Article abstract of DOI:10.1021/jo8027906

(Chemical Equation Presented) Ether cleavage was carried out on arene bearing a diazonium salt. The deprotection takes place with boron tribromide under very mild conditions in good yields without affecting the diazonium group.

Full text of DOI:10.1021/jo8027906

SCHEME 1
Deprotection of Arenediazonium
Tetrafluoroborate Ethers with BBr3
Ngoc Hoa Nguyen, Charles Cougnon,* and Fre´de´ric Gohier*
Unite´ de Chimie Organique Mole´culaire et
Macromole´culaire, UMR CNRS 6011, UniVersite´ du Maine,
AVenue OliVier Messiaen, F-72085 Le Mans, France
(Scheme 1). After ether cleavage of diphenyl 10 under classical
conditions (BBr3/CH2Cl2), diazotization of 10c failed leading
to a complex mixture. So, in a second approach, the diazotization
was carried out on the protected catechol 10. Surprisingly, ether
group deprotection succeeded on diazonium salt 10a.
charles.cougnon@uniV-lemans.fr; fgohier@uniV-lemans.fr
ReceiVed December 22, 2008
To the best of our knowledge, the only attempts mentioned
in the literature showing reactions tolerating diazonium groups
were aromatic nucleophilic substitutions described by Hantzch.6
He concluded that 4,6-dibromobenzenediazonium chloride rear-
ranged in alcoholic solvent at room temperature to bromochlo-
robenzenediazonium chlorides due to the strong activating effect
of the diazonium ion group.7 Except for this observation, there
are no other reports on diazonium-abiding chemistry.
Ether cleavage was carried out on arene bearing a diazonium
salt. The deprotection takes place with boron tribromide
under very mild conditions in good yields without affecting
the diazonium group.
The versatility and the efficiency of our original procedure
were established by the use of a wide range of arene diazonium
salts bearing either one, two, or three methoxy groups (Table
1). Most of the diazonium salts with BF4- as couteranions were
known and prepared by standard methods from an amine and
tert-butyl nitrite with BF3 etherate8 or HBF49 in THF or water.
Then, ether deprotection10 was carried out by adding boron
tribromide in dichloromethane to arene diazonium salts in
dichloromethane solution under inert atmosphere. Deprotection
mechanisms11 are well-known; 1 equiv of BBr3 could theoreti-
cally cleave three ether groups. However, an excess of boron
tribromide was used in each case. Infrared spectroscopy showed
Diazonium salts have always aroused much interest as
intermediates in the preparation of aromatic compounds.1 They
are easily synthesized by using either organic or inorganic nitrite
in the presence of an inorganic acid. Stable diazonium salts could
be isolated, but in most cases, they are directly engaged in the
following step due to their moderate half-life2 depending on
the arene substitution pattern and on the counteranion. The major
applications of diazonium salts are their use as either an
electrophile in azo-coupling to form azo dyes3 or as a leaving
group to introduce different functional groups. In the later
application, a Csp2-Csp2 bond can be generated by a palladium
cross-coupling reaction involving the arenediazonium salt as
the electrophilic partner.4 Recently, these salts also have been
extensively used to modify carbon and metallic surfaces by
electrochemical reduction.5 The major advantage of this ap-
proach is the possibility to introduce numerous functional groups
on different surfaces. For the use in our studies on electrode
derivatization via diazonium salts electrochemistry, the aryl-
diazonium salt 10b bearing a catechol moiety was prepared
+
the expected band around 2200 cm-1 corresponding to the N2
vibration when the arene diazonium salt was synthesized. After
ether cleavage, this band was still present, demonstrating that
the diazonium salt was not affected by the subsequent depro-
tection step. For dimethoxy and trimethoxyarenes (entries 7 and
9-11, Table 1), the reaction proceeded rapidly and could be
done at room temperature while arenes substituted by one
methoxy para to the diazonium group seemed more difficult to
cleave and needed a high temperature and longer reaction time.
In this case, the deprotection can be rationalized with the
diazonium and methoxy resonance effects with the phenyl ring.
The oxygen lone pair electrons are delocalized to the diazonium
ion group, which is thereby stabilized (Figure 1). Oxygen
electrons are less available and the reaction is slower. For the
m-methoxybenzene diazonium salt 2a (Figure 1), the diazonium
group is not resonance stabilized, so the compound is not stable
and deprotection attempts lead to degradation of the starting
compound.
(1) (a) Lindsay, R. In ComprehensiVe Organic Chemistry, 2nd ed.; Barton,
S. D., Ollis, W. D., Sutherland, I. O., Eds.; Pergamon Press: Oxford, UK, 1979;
Vol. 2, p 154. (b) Zollinger, H. Diazo Chemistry I: Aromatic and Heteroaromatic
Compounds; Wiley: New York, NY, 1994. (c) The Chemistry of Diazonium and
Diazo Groups; Patai, S., Ed.; Wiley: New York, 1978.
(2) (a) Bartsch, R. A.; Haddock, N. F.; McCann, D. W. Tetrahedron Lett.
1977, 43, 3779. (b) Hashida, Y.; Matsui, K. Bull. Chem. Soc. Jpn. 1980, 53,
551.
(6) (a) Hantzsch, A. Ber. Dtsch. Chem. Ges. 1897, 30, 2334. (b) Hantzsch,
A.; Smythe, J. S. Ber. Dtsch. Chem. Ges. 1900, 33, 505.
(3) Zollinger, H. Color Chemistry. In Synthesis, Properties, and Applications
of Organic Dyes and Pigments, 3rd revised ed.; Wiley-VCH Verlag: Zu¨rich,
Switzerland, 2003.
(7) Bunnett, J., F.; Zhaler, R., E. Chem. ReV. 1951, 49, 308.
(8) Yu, B.-C.; Shirai, Y.; Tour, J. M. Tetrahedron 2006, 62, 10303.
(9) Beckwith, A. L. J.; Meijs, G. F. J. Org. Chem. 1987, 52, 1922.
(10) Bhatt, M. V.; Kulkarni, S. U. Synthesis 1983, 249.
(4) Roglans, A.; Pla-Quintana, A.; Moreno-Manas, M. Chem. ReV. 2006, 106,
4622.
(5) Pinson, J.; Podvorica, F. Chem. Soc. ReV. 2005, 34, 429.
(11) Benton, F. L.; Dillon, T. E. J. Am. Chem. Soc. 1942, 64, 1128.
10.1021/jo8027906 CCC: $40.75
Published on Web 04/10/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 3955–3957 3955

TABLE 1. Synthesis of Diazonium Salts and Ether Cleavage with BBr3
d
a Yield of isolated compounds. b Compound not obtained (degradation). c Crude yield. The counterion BF4 has been exchanged with Br-.
-
SCHEME 2
FIGURE 1. Resonance structure of p- and m-methoxybenzenediazo-
for reaction with boron tribromide. The starting material was
completely recovered after one day at 40 °C while in the
literature, it is specified that methoxynaphthalene led to naphthol
in 35 min at room temperature with 1 equiv of BBr3.15 An
increase in temperature to 70 °C did not lead to the naphthol
derivative and proton NMR showed the appearance of unidenti-
fied products. Another limitation of the reaction is that the
presence of electron-withdrawing groups such as nitro or acid
functions (entries 4 and 9) makes the diazonium salt unstable
and the expected compounds were not obtained or had low
yields.
Boron tribromide seems to react more easily with dimethoxy-
or trimethoxyarenediazonium salts (entries 7 and 11). We can
suppose that the first reaction with BBr3 takes place with the
m-methoxy not involved in resonance with the diazonium group
(Scheme 2). Then the close proximity of the boron moiety and
the p-methoxy afforded the benzobromodioxoborole, which can
be hydrolyzed.
nium salts.
The participation degree of the diazonium group with the ring
resonance could be analyzed by IR spectroscopy since the N-N
triple bond order is frequency dependent.12,13 A lower IR
frequency will indicate a lower N2 triple bond14 character and
a stronger resonance stabilization. All the vibrational band
frequencies of the diazonium group of 1a,b to 11a,b have been
collected in Table 1.
In the case of 5a, the nitrogen of the pyridine is electroneg-
ative, which raises the diazonium IR band frequency (Vj ) 2283
cm-1). After deprotection, analysis confirmed the lactam forma-
tion and in IR spectroscopy, a spectacular frequency shift was
+
observed due to the resonance between N2 and lactam. We
also point out that the diazonium group of the naphthalene
+
derivative 6a showed a low-frequency IR. This shift in the N2
frequency indicates that the oxygen lone pairs are unavailable
Application of this deprotection method to methylenedioxy
(entry 8) worked similarly to methyl ether cleavage (entry 7)
(12) Whetsel, K. B.; Hawkins, G. F.; Johnson, F. E. J. Am. Chem. Soc. 1956,
78, 3360.
(13) Cox, R. J.; Kumamoto, J. J. Org. Chem. 1965, 30, 4254.
(14) Moriguchi, T.; Sakata, K.; Tsuge, A. J. Chem. Res. (S) 1999, 604.
(15) Punna, S.; Meunier, S.; Finn, M. G. Org. Lett. 2004, 6, 2777.
3956 J. Org. Chem. Vol. 74, No. 10, 2009

3′,4′-Dihydroxybiphenyl-4-diazonium Salt (10b). 10b was
prepared according to the general procedure from 10a. Yellow
but needed a longer reaction time at 40 °C. For nonconjugated
methoxy groups (entry 10) deprotection takes place under very
mild conditions.
In conclusion, we have shown that arenediazonium tetrafluo-
roborate ethers can be deprotected efficiently by BBr3 under
mild conditions in good yields without affecting diazonium salts.
1
powder, mp 134 °C. IR (film) 3059, 2248, 1573, 804 cm-1. H
NMR (DMSO) δ 8.57 (d, J ) 9.1 Hz, 2 H), 8.14 (d, J ) 9.1 Hz,
2 H), 7.31 (m, 2H), 6.94 (d, J ) 8.6 Hz, 1 H). 13C NMR (DMSO)
δ 151.3, 148.5, 145.7, 132.9 (2 × C), 127.6 (2 × C), 126.7, 119.9,
116.1, 114.4, 109.8.
Acknowledgment. We thank the Ministere de l’Education
Nationale et de la Recherche for the fellowship for N.H.N. and
M. Z. Gohier and V. J. C. Cougnon for their technical assistance.
Experimental Section
General Procedure: For Ether Cleavage of 3a-11a. The
methoxyarene diazonium salt (1 mmol, 1 equiv) in 3 mL of CH2Cl2
and 3 mL of toluene was placed in a flask. Then 1 M boron
tribromide in CH2Cl2 (3 mmol, 3 equiv) was slowly added at room
temperature and the solution (or suspension) was stirred for the
time and temperature indicated in Table 1. After cooling, MeOH
(1 mL) was added. The mixture was stirred for another 5 min and
concentrated under reduced pressure to give a dark residue, which
was recrystallized from methanol/ether.
Supporting Information Available: General information,
characterization data for compounds 1a-11a, 1b, 3b, 5b, and
7b-11b along with copies of 1H and 13C NMR of all
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO8027906
J. Org. Chem. Vol. 74, No. 10, 2009 3957