Equilibrium acidities and homolytic bond dissociation energies of N-H and/or O-H bonds in N-phenylhydroxylamine and its derivatives

Article abstract of DOI:10.1021/ja960152n

The equilibrium acidities (pK(HA) values) in DMSO of the following hydroxylamines have been measured: (1) N-phenylhydroxylamine and its p-bromo and p-cyano derivatives, (2) N-benzyl-N-phenylhydroxylamine and its p-bromo and p-cyano derivatives, (3) O-benzyl-N-phenylhydroxylamine, (4) N-benzoylphenylhydroxylamine and its p-bromo and p-cyano derivatives, and (5) N-hydroxylpiperidine. The BDEs of the O-H and/or N-H bonds in these 11 weak acids have been estimated by combining their pK(HA) values with the oxidation potentials of their conjugate bases according to the following equation: BDE(HA) = 1.37pK(HA) + 23.1E(ox)(A^-) + 73.3 kcal/mol.

Full text of DOI:10.1021/ja960152n

VOLUME 118, NUMBER 37
SEPTEMBER 18, 1996
© Copyright 1996 by the
American Chemical Society
Equilibrium Acidities and Homolytic Bond Dissociation
Energies of N-H and/or O-H Bonds in
N-Phenylhydroxylamine and Its Derivatives
Frederick G. Bordwell* and Wei-Zhong Liu
Contribution from the Department of Chemistry, Northwestern UniVersity, 2145 Sheridan Road,
EVanston, Illinois 60208-3113
ReceiVed January 17, 1996X
Abstract: The equilibrium acidities (pKHA values) in DMSO of the following hydroxylamines have been measured:
(1) N-phenylhydroxylamine and its p-bromo and p-cyano derivatives, (2) N-benzyl-N-phenylhydroxylamine and its
p-bromo and p-cyano derivatives, (3) O-benzyl-N-phenylhydroxylamine, (4) N-benzoylphenylhydroxylamine and its
p-bromo and p-cyano derivatives, and (5) N-hydroxylpiperidine. The BDEs of the O-H and/or N-H bonds in
these 11 weak acids have been estimated by combining their pKHA values with the oxidation potentials of their
conjugate bases according to the following equation: BDEHA ) 1.37pKHA + 23.1Eox(A-) + 73.3 kcal/mol.
Introduction
A comparison of the acidities of six series of analogous
oxygen, nitrogen, and carbon acids in DMSO solution and the
gas phase has shown that an intrinsic element effect usually
causes nitrogen acids to be more acidic than carbon acids by
an average of 17 ( 5 kcal/mol and oxygen acids to be more
acidic than nitrogen acids by a like amount.1 (Henceforth, kcal/
mol will be abbreviated as kcal.) It is conceivable, then, that
either (a) an element effect could cause N-phenylhydroxylamine
(1) to ionize as an oxygen acid in DMSO, i.e.,
One purpose of the present paper was, therefore, to compare
the heterolytic cleavages of the N-H and O-H bonds (acidities)
in PhNHOH and its derivatives to see whether it ionizes in
DMSO as an N-H acid, an O-H acid, or both an N-H and
O-H acid.
Benzoylation of PhNHOH gives N-phenylbenzohydroxamic
acid, PhCON(Ph)OH. Both hydroxylamines2 and their acyl
derivatives, hydroxamic acids,3 are known to give strongly
stabilized nitroxyl radicals, PhN(R)O• and PhCON(Ph)O•, on
homolytic cleavage of their O-H bonds. A second purpose of
the present paper was to compare the stabilities of these two
or (b) that the delocalization of the negative charge in the
PhN(OH)- nitranion into the phenyl ring could cause it to ionize
as a nitrogen acid, i.e.,
(2) (a) Sutherland, J. O. In ComprehensiVe Organic Chemistry; Barton,
D., Ollis, W. P., Eds.; Pergamon Press: New York, 1979; Vol. 22, pp 185-
218. (b) Aurich, H. G. In The Chemistry of Amino, Nitroso and Nitro
Compounds and Their DeriVatiVes; Patai, S., Ed.; Wiley: New York, 1987;
Part I, p 565.
X Abstract published in AdVance ACS Abstracts, September 1, 1996.
(1) Bordwell, F. G.; Fried, H. E.; Hughes, D. L.; Lynch, T.-Y.; Satish,
A. V.; Whang, Y. E. J. Org. Chem. 1990, 55, 3330-3336.
S0002-7863(96)00152-7 CCC: $12.00 © 1996 American Chemical Society

8778 J. Am. Chem. Soc., Vol. 118, No. 37, 1996
Bordwell and Liu
Table 1. Equilibrium Acidities of N-Phenylhydroxylamines,
N-Phenylbenzohydroxamic Acids, and Benzyl Alcohols at 25 °C
Determined by the Overlapping Indicator Methoda
24.2 + log 3.5/2.5) and 24.7 () 24.2 + log 3.5/1), respectively,
i.e., about 30% of 1a and 70% of 1b will be present at
equilibrium:
indicator (pKIn)b
pKHA(SD
c
no.
acid
1. PhNHOH
TNH (24.3)
9-methylfluorene (22.6)
CNAH (18.9)
TNH (24.3)
TNH (24.3)
PhSO2Bz (23.43)
p-CF3C6H4CH2SO2Ph (20.2) 19.4 ( 0.1
p-NCC6H4CH2SO2Ph (18.5) 19.0 ( 0.1
24.2 ( 0.1
2. p-BrC6H4NHOH
3. p-NCC6H4NHOH
4. PhN(Bz)OH
22.9 ( 0.07
18.6 ( 0.1
23.87 ( 0.08
23.48 ( 0.05
22.7 ( 0.1
5. PhNHOBz
6. p-BrC6H4N(Bz)OH
7. p-NCC6H4N(Bz)OH
8. PhCON(Ph)OH
9. PhCON(p-BrC6H4)OH Ph2CHCN (17.5)
10. PhCON(p-NCC6H4)OH (MeSO2)2CH2 (15.01)
11. c-C5H10NOH
12. C6H5CH2OH
13 p-ClC6H4CH2OH
14 p-CF3C6H4CH2OH
This is consistent with the observation that PhNHOH failed
to exibit appreciable homo-H-bonding during the titration, which
indicates it acts more like an N-H acid than an O-H acid.
(Experiments have shown that anilines fail to exibit homo-H-
bonding,7 in contrast to O-H acids, which exibit strong homo-
H-bonding5).
17.85 ( 0.1
14.65 ( 0.1
29.80 ( 0.01
26.93 ( 0.01
26.92 ( 0.03
26.71 ( 0.03
TH (30.6)
PXH (27.90)
MCLPXH (26.6)
MCLPXH (26.6)
a See ref 4 and Experimental Section. b Indicators or standard acids
used with their pKa values: TNH ) 1,1,3-triphenyl-2-azapropene,
CNAH ) 4-chloro-2-nitrophenol, TH ) triphenylmethane, PXH )
9-phenylxanthene, MCLPXH ) 9-(m-chlorophenylxanthene. c Mea-
sured pKa corrected for homo-H-bonding5 and corresponding standard
deviation.
The conclusion that PhNHOH behaves primarly as an N-H
acid was supported further by the similarity of the effects of
p-Br and p-CN substituents on the acidities of PhNHOH and
PhNH2, thus, the slope of a three-point Hammett plot observed
for the pKHA values for p-GC6H4NHOH vs σp-,6 with G ) H,
Br, and CN, gave a rho (F) value of 5.6, which is the same as
types of nitroxyl radicals by measuring the BDEs of the O-H
bonds in their N-O-H precursors.
the F value obtained for a plot of the pKHA values for anilines
-
in DMSO7 vs σp
.
The slope of a plot of the pKHA values for p-GC6H4N(Bz)-
OH acids vs σp is not much smaller (F ) 4.5) despite the
-
Results and Discussion
separation of the acidic site from the benzene ring by an
intervening nitrogen atom. In contrast, the damping effect of
the CH2 group in GC6H4CO2H and GC6H4CH2CO2H reduces
the Hammett F value from 1.0 to 0.43.8 The unexpectedly high
sensitivity of the pKHA’s of p-GC6H4N(Bz)OH acid to p-
substituent effects may be due (a) to better transmission of
charge by N than CH2 or (b) to four-electron repulsions in the
p-GC6H4N(Bz)O- anion (4a T 4b), that encourages delocal-
ization of the electrons on nitrogen into the substituent-bearing
benzene ring.
Comparison of the Acidities of the N-H and O-H Bonds
in N-Phenylhydroxylamine and Its Derivatives. The equi-
librium acidities of N-phenylhydroxylamine and some of its
derivatives and related compounds that are summarized in Table
1 provide the information needed to answer the question
concerning the relative N-H and O-H acidities of N-phenyl-
hydroxylamine.
The pKHA values for N-benzyl-N-phenylhydroxylamine, PhN-
(Bz)OH (2), an O-H acid, and O-benzyl-N-phenylhydroxyl-
amine, PhNHOBz (3), an N-H acid (entries 4 and 5, respec-
tively, in Table 1), differ but little, the N-H acid being only
about 0.4 pKHA unit stronger than the O-H acid. Both are
slightly more acidic than PhNHOH (1) (entry 1), an effect
attributable to the electron-withdrawing field/inductive effect
of the benzyl group.6 These results indicate that in DMSO
solution the following equilibrium will be established.
Comparison of the BDEs of the N-H and O-H Bonds
in N-phenylhydroxylamine with Those in Anilines and
Alcohols. The literature values of 88,9a 86,9b and 899c (except
90.69d) kcal for the N-H bond in aniline are not consistent with
a recent value of 87.3 kcal10 reported for diphenylamine, because
the substitution of a phenyl group for a hydrogen atom on
nitrogen in aniline is expected to cause a sizable decrease in
BDE. Our BDE for aniline of 92.4 kcal, estimated by eq 1, is
the average of the BDEs of aniline itself (92.3 kcal) and its
p-Me (92.0 kcal), p-Cl (92.5 kcal), m-Cl (92.5 kcal), and p-Br
(92.4 kcal) derivatives.11
If the acidity difference of N-H bond and O-H bond in
PhNHOH can be assumed to be approximately equal to the
acidity difference of N-H bond in PhNHOBz and O-H bond
in PhN(Bz)OH, i.e., 0.4 pKHA unit, the true pKHA values of N-H
and O-H bonds in PhNHOH can be estimated to be 24.3 ()
BDEHA ) 1.37pKHA + 23.1Eox(A-) + 73.3 kcal/mol (1)
(3) (a) Bordwell, F. G.; Harrelson, J. A., Jr.; Lynch, T. Y. J. Org. Chem.
1990, 55, 3337-3341. (b) Perkins, M. J.; Berti, C.; Brooks, D. J.; Grierson,
L.; Grimes, J. A.-M.; Jenkins, T. C.; Smith, S. L. Pure Appl. Chem. 1990,
62, 195-200, and references cited therein.
(4) (a) Matthews, W. S.; Bares, J. E.; Bartmess, J. E.; Bordwell, F. G.;
Cornforth, F. J.; Drucker, G. E.; Margolin, Z.; McCallum, R. J.; McCollum,
G. J.; Vanier, N. R. J. Am. Chem. Soc. 1975, 97, 7006-7014. (b) Bordwell,
F. G.; McCallum, R. J.; Olmstead, W. N. J. Org. Chem. 1984, 49, 1424-
1427.
(7) Bordwell, F. G.; Algrim, D. J. J. Am. Chem. Soc. 1988, 110, 2964-
2968.
(8) Hammett, L. P. Physical Organic Chemistry, 2nd ed.; McGraw-
Hill: 1970; p 367.
(9) (a) McMillen, D. F.; Golden, D. M. Annu. ReV. Phys. Chem. 1982,
33, 483-532. (b) Colussi, A. J.; Benson, S. W. Int. J. Chem. Kint. 1978,
10, 1139-1149. (c) Jonsson, M.; Lind, J.; Eriksen, T. E.; Merenyi, G J.
Am. Chem. Soc. 1994, 116, 1423. (d) Denisov, E. T.; Khudyakov, I. V.
Chem. ReV., 1987, 87, 1313.
(10) Varlamov, V. J.; Denisov, E. T. Dokl. Akad. Nauk. USSR 1987,
293, 126-128.
(5) Olmstead, W. N.; Margolin, Z.; Bordwell, F. G. J. Org. Chem. 1980,
45, 3295-3299.
(6) Hansch, C.; Leo, A.; Taft, R. W. Chem. ReV. 1991, 91, 165-195.

Equilibrium Acidities in N-Phenylhydroxylamine
J. Am. Chem. Soc., Vol. 118, No. 37, 1996 8779
Table 2. Homolytic Bond Dissociation Energies of
N-Phenylhydroxylamines and N-Phenylbenzohydroxamic Acids
acetic acid, phenol, and tert-butyl alcohol are linearly related
to their pKHA values in DMSO.15 The hydrogen bond strength
of PhN(Bz)OH (2) in DMSO (pKHA) 24) should on this basis
a
-
no.
acid
PhNHOH
p-BrC6H4NHOH
p-NCC6H4NHOH
PhN(Bz)OH
pKHA
Eox(A
BDEHA
)
be about midway between that of phenol, 7.2 kcal15a (pKHA
)
1.
2.
3.
4.
5.
6.
7.
8.
9.
24.2
22.9
18.58
23.87
23.48
22.7
19.4
19.0
17.85
14.65
29.80
-1.255
-1.146
-0.898
-1.354b
-1.284
-1.259b
-0.976b
-0.649b
-0.600b
-0.395b
-1.610c
77.5
78.2
78.0
74.8
75.8
75.4
77.3
84.2
84.0
84.2
77.0
18) and tert-butyl alcohol, 4.7 kcal15a (pKHA) 32.2), i.e., about
5-6 kcal. The BDE of the O-H in PhN(Bz)OH (2) estimated
to be 74.8 kcal by eq 1 could, on this basis, be as low as 70
kcal.
PhNHOBz
p-BrC6H4N(Bz)OH
p-NCC6H4N(Bz)OH
PhCON(Ph)OH
PhCON(p-BrC6H4)OH
PhCON(p-NCC6H4)OH
c-C5H10NOH
The BDEs of the O-H bonds in the p-Br and p-CN
derivatives are 0.6 and 2.5 kcal higher than that of 2. Examina-
tion of the two terms in eq 1 shows that structural changes in
a series of weak acids can cause an increase in the BDE either
(a) by increasing the pKHA or (b) by causing an anodic (positive)
shift in Eox(A-). The p-Br and p-CN substituents both cause a
decrease in pKHA accompanied by anodic shift in Eox(A-). For
the stronger electron-withdrawing p-CN group, the pKHA
decrease is 4.5 pKHA units (6.1 kcal) and anodic Eox(A-) shift
is 378 mV (8.7 kcal). The 2.5 kcal increase in BDE is therefore
caused by the anodic shifts in Eox(A-), which overshadows the
decrease in pKHA. Introduction of a p-CN group into phenol,
thiophenol, or aniline also causes increases in BDE. These
increases have been attributed to decrease in ground-state
energies resulting from the stablizing effects of dipole-dipole
interactions of the p-CN group with the acidic function,16
following the lead of Clark and Wayner.17,18 This rationalization
can also be applied to the present case although the O-H group
is not directly involved, (5a and 5b) (the remote substituent
effect on the highly stablized nitroxide radical is expected to
be relatively small).
10.
11.
a Irreversible oxidation potentials measured in DMSO with 1-3 mM
concentrations of HA and 0.1 M Et4N+BF4- electrolyte at a sweep rate
of 100 mV s-1, and referred to the ferrocene/ferrocenium couple unless
otherwise indicated. b Partially reversible at 10 V/s. c n-Bu4N+PF6- as
electrolyte.
Our BDE for diphenylamine of 87.4 kcal is the average of
the BDEs of diphenylamine itself (87.5 kcal) and its p-Me (86.9
kcal), m-Me (87.6 kcal), and p,p′-diBr (87.8 kcal) derivatives
plus iminodibenzyl (87.0 kcal). The 5 kcal difference in the
average values for PhNH-H and Ph2N-H agrees well with
the 6 kcal difference between the BDEs of PhCH2-H (88 kcal)
and Ph2CH-H (82 kcal).11
The BDE of 75.8 kcal for the N-H bond in PhNHOBz (3)
and the BDE of ∼77.5 kcal for the N-H bond in PhNHOH (1)
(Table 2) are about 16 kcal weaker than the N-H bond in
aniline. This is attributed to stablization of the corresponding
radical by delocalization of the odd electron (e.g., 1a•- 1c•).
The BDE of the O-H bond in N-benzyl-N-phenylhydroxyl-
amine is weaker than that in an analogous alcohol, C6H5CH2-
OH,9a by about 30 kcal, which means that the delocalizing effect
of an adjacent nitrogen in weakening the O-H bond is much
greater than the weakening of an adjacent N-H bond by an
O-H group (16 kcal). This is consistent with the much greater
donor properties of nitrogen than oxygen together with the much
greater ability of oxygen than nitrogen to accommodate a
negative charge.
The BDEs of the O-H bonds in hydroxylamines can also
be estimated by eq 1, but these estimates may need to be
corrected for a solvation effect. Griller et al. have suggested
that in dipolar solvents the BDEs of O-H bonds, such as that
in phenol, will be higher than the gas-phase BDE by an amount
equal to that required to break the polar bonds to the solvent.14
Examination of the literature has shown that the strengths of
the solvent hydrogen-bonds to the O-H bonds in benzoic acid,
(11) Bordwell, F. G.; Cheng, J.-P.; Ji, G.-Z.; Satish, A. V.; Zhang, X.-
M. J. Am. Chem. Soc. 1991, 113, 9790-9795. (Originally the Eox(A-) values
were referenced to the Ag/AgI electrode and the constant 56 kcal was used;
when referenced to the Fc/Fc+ couple the constant becomes 73.3 kcal).
Irreversible Eox(A-) values were usually found to agree with reversible E1/2
values within 100 mV or better when such comparsons are possible.12 In
this and subsequent papers,13 BDEs using irreversible Eox(A-) values have
been shown to give agreement with gas phase BDEs to (3 kcal/mol, or
better in most instances (the error between relative values in a series of
closely related compounds will be much smaller, ca. (0.5 kcal/mol
experimental error).
(12) (a) Venimadhavan, S.; Amarnath, K.; Harvey, N. G.; Arnett, E. M.
J. Am. Chem. Soc. 1992, 114, 221. (b) Bordwell, F. G.; Harrelson, J. A.;
Lynch, T.-Y. J. Org. Chem. 1990, 55, 3337-3341.
(13) (a) Bordwell, F. G.; Zhang, S. J. Am. Chem. Soc. 1995, 117, 4858-
4861. (b) Bordwell, F. G.; Satish, A. V.; Zhang, S.; Zhang, X.-M. Pure
Appl. Chem. 1995, 67, 735-740 and references cited therein.
(14) (a) Kanabus-Kaminska, J. M.; Gilbert, B. C.; Griller, D. J. Am.
Chem. Soc. 1989, 111, 3311. (b) Wayner, D. D. M.; Lusztyk, E.; Page, D.;
Ingold, K. U.; Mulder, P.; Laarhonen, L. J. J.; Aldrich, H. S., J. Am. Chem.
Soc. 1995, 117, 8737-8744.
Entry 11 in Table 1 shows that the equilibrium acidity (pKHA
of the O-H bond in N-hydroxypiperidine (6) is 29.8 in DMSO,
which is the same as that of the O-H bond in ethanol and only
)
(15) (a) Arnett, E. M.; Jaris, L.; Mitchell, E. J.; Murty, T. S. S. R.; Gorrie,
T. M.; Schleyer, P. v. R. J. Am. Chem. Soc. 1970, 92, 2365. (b) Rosenberg,
M. S.; Iogansen, A. V.; Mashkovsky, A. A.; Odinokov, S. E. Spectroscopy
Lett. 1972, 5, 75-80.
(16) Bordwell, F. G.; Zhang, X.-M.; Satish, A. V. J. Am. Chem. Soc.
1994, 116, 6605-6610.

8780 J. Am. Chem. Soc., Vol. 118, No. 37, 1996
Bordwell and Liu
0.4 pKHA unit greater than that of the O-H bond in isopropyl
alcohol.5 It was at first sight surprising to see that the greater
electronegativity of the nitrogen atom bonded to oxygen in 6
had not induced a greater acidity on the O-H bond than that
caused by the carbon atom joined to the oxygen atom in ethanol.
acidity of the N-H bond in 1 is about 6.4 pKHA units (8.8 kcal)
stronger than the N-H bond in aniline, and the acidity of the
O-H bond in 1 is about 3 pKHA units (4 kcal) stronger than
that in benzyl alcohol. The BDE of the N-H bond in 1 is about
15 kcal weaker than that in aniline and the O-H bond in 1 is
about 30 kcal weaker than that in benzyl alcohol. In other words
an adjacent nitrogen atom weakens an O-H bond by about 15
kcal/mol more than an adjacent oxygen atom weakens an N-H
bond. The O-H bond in N-benzylphenylhydroxylamine (2) is
about 10 kcal weaker than that in N-phenylbenzohydroxamic
acid.
Experimental Section
It follows that an acid-weakening effect must be present in 6
that offsets this N vs C (acid strengthening) element effect. The
four-electron repulsion in the N-OH moiety is expected to
increase the ground-state energy of the undissociated acid (6),
relative to that in ethanol, which should be acid strengthening,
but the increase in ground-state energy in the anion, 6a-, will
be greater than that in the undissociated acid because of the
negative charge, and this acid-weakening effect evidently offsets
the nitrogen vs carbon element effect.
N-Hydroxypiperidine 6 (entry 11) has a pKHA 5.6 unit (7.7
kcal) higher than that of PhNHOH and 6.3 pKHA unit (8.7 kcal)
higher than that of PhN(Bz)OH, but the BDE of its O-H bond
is almost identical with that of PhNHOH and only 2.2 kcal
higher than that of PhN(Bz)OH. This means that, although the
O-H bond in 6 is 7.7-8.7 kcal stronger toward heterolytic
cleavage than the O-H bond in 1 or 2, the strength of the O-H
bond in 6 is not much different from that of the O-H bonds in
1 or 2 toward homolytic cleavage.
NMR spectra were recorded on a Gemini XL-300 (300 MHz) or
XLA 400 (400 MHz) spectrometer. Melting points were measured on
a Thomas Hoover capillary melting point apparatus and are uncorrected.
Equilibrium acidities in DMSO were determined by the overlapping
indicator method4 at ambient temperatures and are summarized in Table
1. The concentrations of the acid and the indicator used in pKHA
measurements were typically between 0.5-5.0 mM. The pKHA and
pKAHA values should be independent of the concentrations used.4,5 All
-
the pKHA measurements were based on 2-4 titrations; each had 3-5
points with different HA/A- ratios. Measurement of pKAHA value
-
requires at least 5 points with HA/A- ratio within a range from 1:3 to
3:1.5
The O-H acids were found to form strong homo-hydrogen-bonds
(the observed pKHA values for an acid will depend on the ratio of the
acid and its conjugate anion if the acid and its conjugate anion form
strong homo-H-bond5), e.g., the homo-H-bonding constant (pKAHA
)
-
for PhN(OH)Bz, c-C5H10NOH, PhCH2OH, p-ClC6H4CH2OH, and
p-CF3-C6H4CH2OH were found to be 2.97 ( 0.01, 3.27 ( 0.03, 3.65
( 0.02, 3.73 ( 0.12, and 3.59 ( 0.11, respectively. Since the
corresponding program was not available for titrations requiring the
-
use of standard acids, the pKAHA values for p-G-C6H4N(Bz)OH (G )
Cl, CN) and p-G-C6H4N(COPh)OH (G ) H, Cl, CN) acids were not
obtained. The effect of homo-hydrogen-bonding on pKHA values for
these acids was avoided by measuring the pKHA values at points where
the ratios of the concentration of the acid and the conjugate anion were
close to 1:1.5 The N-H acids did not exibit homo-H-bonding as
The Effect of N-Benzoylation on the BDE of the O-H
Bond in Phenylhydroxylamine. Examination of entry 8 in
Table 2 shows that N-benzoylation of PhNHOH to give
N-phenyl-benzohydroxamic acid decreases the pKHA by 5.2 units
(7.1 kcal) but increases the BDE by about 6.5 kcal caused by
a 14 kcal anodic shift in Eox(A-). The effect of substituting
the benzoyl group on nitrogen contrasts sharply with the effect
of substituting a benzyl (Bz) group which has but little effect
on the pKHA of PhNHOH and slightly weakens the O-H bond.
The powerful electron-withdrawing effect of the carbonyl group
is of course responsible. It mitigates the donor properties of
nitrogen and introduces a strong acid-strengthening field/
inductive effect. The strength of the O-H bond is increased
homolytically as a consequence of the decreased ground-state
energy of the molecule but still remains weaker than the O-H
bond in alcohols by about 20 kcal. The presence of a p-CN
group in the phenyl ring of the PhCON(p-NCC6H4)OH increases
the acidity of the O-H group by about 6 kcal but has no effect
on the homolytic bond energy.
expected,7 e.g., the pKAHA values for PhNHOBz were found to be less
-
than 0.5.
Sutherland reported that hydroxylamines are quite unstable in alkaline
aqueous solutions.19 However, we found that the hydroxylamines and
hydroxamic acids we used were stable enough to perform titrations
and oxidation potential measurements in DMSO solution.
Oxidation potentials were measured by a conventional cyclic
voltammetric instrument, as described previously.11 The working
electrode (BAS) consists of a 1.5 mm diameter platinum disk embedded
in a cobalt glass seal. It was polished with 0.05-µm Fisher polishing
alumina and rinsed with ethanol and dried before each run. The counter
electrode was platinum wire (BAS). The reference electrode was Ag/
AgI, and the redox potentials reported were referenced to ferrocene/
ferrocenium couple. Tetraethylammonium tetrafluoroborate or tetra-
n-butylammonium hexafluorophosphate was used as the supporting
electrolyte. The electrochemical experiments were carried out under
an argon atmosphere.
Material. Nitrobenzene, p-bromonitrobenzene, p-cyanonitroben-
zene, N-hydroxylpiperidine were purchased from Aldrich and used as
received. N-Phenylbenzohydroxamic acid (Eastman Organic Chemi-
cals) was purified by recrystallization from benzene-hexane solution.
Tetraethylammonium tetrafluoroborate was recrystallized from absolute
alcohol and dried at 110 °C at 0.1τ for 24 h.
Summary and Conclusions
Substituted N-phenylhydroxylamines were prepared by a modified
method of Crumbliss and Brink.20 Typically, into an aqueous solution
(30 mL) of ammonium chloride (20 mmol) was added a hot alcohol
solution (20 mL) of substituted nitrobenzene (20 mmol), and the mixture
was stirred vigorously to form a milky suspension. Then 22 mmol of
The N-H bond in PhNHOH (1) is estimated to have a pKHA
of 24.3 compared to 24.7 for the O-H bond, based on the
relative acidities of PhN(Bz)OH (2) and PhNH(OBz) (3). The
(17) Clark, K. B.; Wayner, D. D. M. J. Am. Chem. Soc. 1991, 113, 9363.
(18) Ru¨chardt, C. Angew. Chem., Int. Ed. Engl. 1970, 9, 830-843 and
Nicholas, A. M. P.; Arnold, D. R. Can. J. Chem. 1984, 62, 1850 have also
called attention to the importance of changes in ground state energies in
affecting bond dissociation energies.
(19) Sutherland, I. O. In ComprehensiVe Organic Chemistry Barton, D.,
Ollis, W. D., Eds.; Pergamon Press: 1979; Vol. 2, pp 185-218.
(20) Brink, C. P.; Crumbliss, A. L. J. Org. Chem. 1982, 47, 1171.

Equilibrium Acidities in N-Phenylhydroxylamine
J. Am. Chem. Soc., Vol. 118, No. 37, 1996 8781
zinc dust was added during 20 min at 70 ( 5 °C, and the mixture was
stirred for an additional 20 min. The zinc oxide formed was removed
by filtration, and the resulting solution was extracted with 30 mL of
ether. The organic layer was dried with CaCl2. After the solvent was
stripped off, the crude substituted N-phenylhydroxylamine was recrys-
tallized from benzene-hexane solution and dried at 0.1τ / 25 °C for 1
h. The samples thus obtained were found to be stable at -10 °C for
several weeks. The yield and the properties of the N-phenylhydroxyl-
amines were characterized as follows: PhNHOH, 60%, mp 82 °C (lit.21
Perronnet et al.:23 To a DMSO (10 mL) solution of N-phenylbenzo-
hydroxamic acid (10 mmol) were added anhydrous K2CO3 (20 mmol),
and benzyl chloride (15 mmol), and the solution was stirred at room
temperature for 48 h. The resulting mixture was poured into 30 mL
of water and extracted with 30 mL of ether. The ether layer was washed
with 30 mL of water, dried with CaCl2, and concentrated under vacuum.
The residue was purified by column chromatography (2:5 ether:hexane)
to give 1.5 g (50%) of O-benzyl-N-phenylhydroxamic acid, mp 85-6
°C, 1H NMR (CDCl3): δ 4.84(2H, s, CH2), 7.1-7.7(15H, m).
A
1
81-2 °C), H NMR (CDCl3): δ 6.5 (2H, br, NHOH), 7.02 (3H, m),
mixture of DMF (6 mL), O-benzyl-N-phenylhydroxamic acid (1.2 g, 4
mmol) and hydrazine hydrate (1 mL) was stirred at 85 °C for 12 h.
The resulting mixture was poured into 20 mL water of and extracted
with 20 mL of ether. The ether layer was washed with 20 mL of water,
dried with CaCl2, and concentrated under vacuum. The residue was
purified by column chromatography (1:5 ether:hexane) to give 0.4 g
7.30 (2H, m). p-BrC6H4NHOH, 75%, mp 92 °C (lit.2191 °C), 1H NMR
(CDCl3): δ 6.1 (2H, br, NHOH), 6.88 (2H, d, J ) 8.7 Hz), 7.39 (2H,
d). p-NCC6H4NHOH, 49%, mp 87 °C (lit.21 86 °C), 1H NMR
(CDCl3): δ 5.6 (1H, s, OH), 7.03 (1H, s, NH), 7.01 (2H, d, J ) 8.5
Hz), 7.54 (2H, d).
1
Substituted N-benzyl-N-phenylhydroxylamines were prepared by
the method of Utzinger.22 Typically, 5 mmol of substituted N-
phenylhydroxylamine was dissolved in 5 mL of ether, mixed with 5
mmol of benzyl chloride and 5 mmol pyridine, and allowed to stand at
room temperature for 48 h. The resulting solution was mixed with 20
mL of water extracted with 10 mL of ether and dried with CaCl2. After
removal of the ether, the crude product was purified by column
chromatography (1:5 ether and hexane as eluent). The properties and
(yield) of the substituted N-benzyl-N-phenylhydroxylamine were
characterized as follows: PhN(OH)Bz (56%), mp 85 °C (lit.22 86 °C),
1H NMR (CDCl3): δ 4.39 (2H, s, CH2), 5.62 (1H, s, OH), 7.04 (1H,
t, J ) 7.4 Hz), 7.22 (2H, d, J ) 7.5 Hz), 7.28-7.45 (7H, m).
p-BrC6H4N(OH)Bz (40%), mp 92-92.5 °C, 1H NMR (CDCl3): δ 4.36
(2H, s, CH2), 5.46 (1H, s, OH), 7.03 (2H, d, J ) 8.7 Hz), 7.15-7.25
(7H, m). Calculated for C13H12BrNO: C, 56.14; H, 4.35; N, 5.04.
Found: C, 55.90; H, 4.35; N, 5.21. p-NCC6H4N(OH)Bz (40%), mp
(50%) of O-benzyl-N-phenylhydroxylamine, mp ∼ -10 °C, H NMR
(CDCl3): δ 4.95 (2H, s, CH2), 6.98 (3H, m), 7.03 (1H, s, NH), 7.31
(2H, m), 7.4-7.55 (5H, m).
Substituted N-phenylbenzohydroxamic acids were prepared by
the method of Ayyanger et al.24 The identities of the compounds were
1
confirmed by their H NMR spectrum. Their yields and the spectral
data were as follows: p-BrC6H4N(OH)COPh, 40%, mp 163 °C (lit.24
163 °C), 1H NMR (CDCl3): δ 7.08 (2H, d, J ) 8.8 Hz), 7.32 (2H, d),
7.42 (5H, m), 9.15 (1H, s, OH). p-NCC6H4N(OH)COPh, 45%, mp
147-8 °C, 1H NMR (CDCl3): δ 7.33 (2H, d), 7.38 (2H, m), 7.47 (3H,
m), 7.57 (2H, d, J ) 8.5 Hz), 9.15 (1H, s, OH).
Acknowledgment. This research was supported by the
donors of the Petroleum Research Fund administered by the
American Chemical Society and by the National Science
Foundation.
1
100-1 °C, H NMR (C6D6): δ 4.1 (2H, s, CH2), 6.02 (1H, s, OH),
6.68 (2H, d, J ) 8.7), 7.0-7.3 (7H, m). Calculated for C14H12N2O:
C, 74.98; H, 5.39; N, 12.49. Found: C, 74.85; H, 5.43; N, 12.51.
N-Phenyl-O-benzylhydroxylamine was prepared by the method of
JA960152N
(23) Perronnet, J.; Girrault, P.; Demoute, J.-P. J. Heterocycl. Chem. 1980,
17, 727.
(21) Peltier, D.; Gueguen, M. J. Bull. Soc. Chim. Fran. 1969, 264.
(22) Utzinger, G. E. Liebigs Ann. Chem. 1944, 556, 50.
(24) Ayyanger, N. R. Brahme, K. C.; Kalkote, U. R.; Srinivasan, K. V.
Synthesis 1984, 938.