Oxidation reactivity channels for 2-(pyridin-2-yl)-N,N-diphenylacetamides

Article abstract of DOI:10.1021/jo701408y

(Chemical Equation Presented) Synthetic routes to 2-(pyridin-2-yl)-N,N- diphenylacetamide and 2-(6-methylpyridin-2-yl)-N,N-diphenylacetamide are described along with results from the chemical oxidation of these compounds with peracetic acid, m-chloroperbe

Full text of DOI:10.1021/jo701408y

Oxidation Reactivity Channels for
2-(Pyridin-2-yl)-N,N-diphenylacetamides
Sylvie Pailloux,† Iris Binyamin,† Lorraine M. Deck,† Brian M. Rapko,‡ Benjamin P. Hay,§
Eileen N. Duesler,† and Robert T. Paine*,†
Department of Chemistry, UniVersity of New Mexico, Albuquerque, New Mexico 87131, Pacific Northwest
National Laboratory, P.O. Box 999, Richland, Washington 99352, and Oak Ridge National Laboratory,
P.O. Box 2008, Oak Ridge, Tennessee 37831
rtpaine@unm.edu
ReceiVed July 10, 2007
Synthetic routes to 2-(pyridin-2-yl)-N,N-diphenylacetamide and 2-(6-methylpyridin-2-yl)-N,N-diphenyl-
acetamide are described along with results from the chemical oxidation of these compounds with peracetic
acid, m-chloroperbenzoic acid, and OXONE. In each case, oxidations generate four products in varying
amounts depending on the oxidant and reaction conditions. Each product has been characterized by
spectroscopic methods and the molecular structures of several of the new compounds have been confirmed
by X-ray crystallography.
Introduction
CH2C(O)NR2,6-9andalkylmalonamides,[RR′NC(O)]2CR′′H,10-17
have been actively examined and each displays potentially useful
characteristics. In our group, we have considered the utility of
There is much interest in the design and synthesis of organic
ligands suitable for selective recognition and separation of
f-blockmetalionsfromaqueoussolutionsviasolventextraction.1-4
These ligands often contain two or more neutral oxygen donor
groups such as phosphine oxides or amides. As examples,
carbamoylmethylphosphonates (CMP), (RO)2P(O)CH2C(O)-
NR2,5 carbamoylmethylphosphine oxides (CMPO), R2P(O)-
(5) Horwitz, E. P.; Martin, K. A.; Diamond, H.; Kaplan, H. SolVent Extr.
Ion Exch. 1986, 4, 449.
(6) Horwitz, E. P.; Martin, K. A.; Diamond, H.; Vandegrift, G. F.;
Schultz, W. W. SolVent Extr. Ion Exch. 1985, 3, 75.
(7) Ozawa, M.; Koma, Y.; Nomura, K.; Tanaka, Y. J. Alloys Compd.
1988, 271-273, 538.
(8) Mathur, J. N.; Murali, M. S.; Natarajan, P. R.; Badhelka, L. P.;
Bannerji, A.; Ramanujam, A.; Dhami, P. S.; Gopalakrishnan, V.; Dhumwad,
R. K.; Rao, M. K. Waste Manage (Amsterdam, Neth.) 1993, 13, 317.
(9) Myasoedov, B. F.; Chmutova, M. K.; Smirnov, I. V.; Shadrin, A. U.
In Global ’93: Future Nuclear Systems: Emerging Fuel Cycles and Waste
Disposal Options; American Nuclear Society: La Grange Park, IL, 1993.
(10) Cuillerdier, C.; Musikas, C.; Hoel, P.; Nigond, L.; Vitart, X. Sep.
Sci. Technol. 1991, 26, 1229.
(11) Tan, X. F.; Wang, Y. S.; Tan, T. Z.; Zhou, G. F.; Bao, B. R. J.
Radioanal. Nucl. Chem. 1999, 242, 123.
(12) McNamara, B. K.; Lumetta, G. J.; Rapko, B. M. SolVent Extr. Ion
Exch. 1999, 17, 1403.
* To whom correspondence should be addressed. Phone: (505) 277-1661.
† University of New Mexico.
‡ Pacific Northwest National Laboratory.
§ Oak Ridge National Laboratory.
(1) Draganic, I. G.; Draganic, Z. D.; Adloff, J. P. Radiation and
RadioactiVity on Earth and Beyond; CRC Press: Boca Raton, FL, 1990.
(2) Nash, K. L.; Madic, C.; Mathur, J. N.; Lacquemont, J. In The
Chemistry of the Actinide and Transactinide Elements; Morss, L. R.,
Edelstein, N. M., Fuger, J., Eds.; Springer: Dordreckt, The Netherlands,
2006; Vol. 4, Chapter 24, pp 2622-2798.
(3) Mathur, J. N.; Murali, M. S.; Nash, K. L. SolVent Extr. Ion Exch.
2001, 19, 357-390.
(4) Nash, K. L. SolVent Extr. Ion Exch. 1993, 11, 729-768.
(13) Lumetta, G. J.; McNamara, B. K.; Rapko, B. M.; Hutchinson, J.
M. Inorg. Chem. 1993, 32, 2164.
10.1021/jo701408y CCC: $37.00 © 2007 American Chemical Society
Published on Web 11/01/2007
J. Org. Chem. 2007, 72, 9195-9202
9195

Pailloux et al.
pyridine and pyridine N-oxide as platforms for the assembly of
selective ligands, and structures of the general types A-F have
been developed.18-31 Ligands E and F form particularly stable
complexes, and derivatives, carrying lipophilic substituents such
as 2-ethylhexyl, provide impressive separations performance for
lanthanides (Ln+3) and Am+3 from strongly acidic HNO3 (>1
M) solutions.31
Results and Discussion
Limited attention has been given to the development of
efficient syntheses for 2-(pyridin-2-yl) acetamides M and, as
far as we are aware, no reports of the corresponding N-oxide
derivatives have appeared. Reich and Levine34 described the
synthesis of M (R ) R′ ) Me, Et, n-Bu and R ) Me, R′ ) Ph)
in low to modest yields from the combination of picolylithium
and the corresponding diorganyl carbamoyl chlorides. Murray,35
as part of broad patent claims, included a description of the
synthesis of N,N-dimethyl-(2-pyridyl) acetamide by using an
aggressive (autoclave, 90 °C, 96 h) amination of ethyl 2-py-
ridylacetate with excess Me2NH/MeOH; however, formation of
other derivatives relevant to our study is not indicated. More
recently, in a general study of heteroaromatic nucleophilic
substitutions by various carbanions via an SRN1 mechanism,
Wolfe and co-workers36 outlined the interaction of the potassium
enolate of N,N-dimethylacetamide with 2-bromopyridine under
photolytic conditions which produced M (R ) R′ ) Me) in
74% yield along with 5% of the double substitution product.
Moloney and co-workers37 also reported a Reformatsky reagent
approach (dibenzylbromoacetamide/Zn) on 2-bromopyridine
with microwave radiation assistance. This reaction gave M (R
) R′ ) Bn) in 73% yield. The only route reported for a wide
variety of N,N-dialkyl derivatives has been summarized in a
patent describing syntheses of 4H-quinolizin-4-one com-
pounds.38 The approach employed peptide coupling methods
with 2-pyridylacetic acid hydrochloride and symmetric and
asymmetric dialkylamines.
Despite these successes, there remain fundamental and
practical interests in further expansion of available extractant
molecules, especially those that might provide a slightly softer
donor environment and more selective separations, e.g., Am/
Cm partitioning. Representative target ligands include acetamido
and propionamido functionalized pyridine and pyridine N-oxide
platforms. In that regard, we have recently reported the syntheses
and coordination chemistry for examples of G-L.32,33 These
results have stimulated efforts to prepare the N,N-diorganyl
acetamide analogues of C-F. Herein we report the syntheses
and oxidation chemistry of the “one-armed” derivatives M.
(14) Spjuth, L.; Liljenzin, J. O.; Hudson, M. J.; Drew, M. G. B.; Iveson,
P. B.; Madic, C. SolVent Extr. Ion Exch. 2000, 18, 1.
(15) Facchini, A.; Amato, L.; Modolo, G.; Nannicini, R.; Madic, C.;
Baron, P. Sep. Sci. Technol. 2000, 35, 1055.
(16) Courson, O.; Lebrun, M.; Malmbeck, R.; Pagliosa, G.; Romer, K.;
Satmark, B.; Glatz, J. P. Radiochim. Acta 2000, 88, 857.
(17) Lumetta, G. J.; Rapko, B. M.; Garza, P. A.; Hay, B. P.; Gilbertson,
R. D.; Weakley, T. J. R.; Hutchinson, J. E. J. Am. Chem. Soc. 2002, 124,
5644.
(18) McCabe, D. J.; Russell, A. A.; Karthikeyan, S.; Paine, R. T.; Ryan,
R. R.; Smith, B. F. Inorg. Chem. 1987, 26, 1230.
(19) Conary, G. C.; Russell, A. A.; Paine, R. T.; Hall, J. H.; Ryan, R. R.
Inorg. Chem. 1988, 27, 3242.
(20) Blaha, S. L.; McCabe, D. J.; Paine, R. T.; Thomas, K. W. Radiochim.
Acta 1989, 46, 123.
(21) Rapko, B. M.; Duesler, E. N.; Smith, P. H.; Paine, R. T.; Ryan, R.
R. Inorg. Chem. 1993, 32, 2164.
(22) Englehardt, U.; Rapko, B. M.; Duesler, E. N.; Frutos, D.; Paine, R.
T. Polyhedron 1995, 14, 2361.
(23) Bond, E. M.; Duesler, E. N.; Paine, R. T.; No¨th, H. Polyhedron
2000, 19, 2135.
(24) Gan, X. M.; Parveen, S.; Smith, W. L.; Duesler, E. N.; Paine, R. T.
Inorg. Chem. 2000, 39, 4591.
In the studies summarized above, no mention was made
regarding the applicability of these methods for the formation
of M (R ) R′ ) Ph) or the outcome of chemical oxidation as
a route to the corresponding N-oxides. Although we are
potentially interested in the N,N-dialkyl derivatives for lipophillic
solvent extraction schemes, we initially focused on obtaining
M (R ) R′ ) Ph) (hereafter labeled as compound 1) and its
N-oxide derivative since aryl derivatized ligands typically
provide better opportunities to obtain well-defined, crystalline
(25) Bond, E. M.; Duesler, E. N.; Paine, R. T.; Neu, M. P.; Matonic, J.
H.; Scott, B. L. Inorg. Chem. 2000, 39, 4152.
(26) Gan, X.; Duesler, E. N.; Paine, R. T. Inorg. Chem. 2001, 40, 4420.
(27) Gan, X.; Paine, R. T.; Duesler, E. N.; No¨th, H. J. Chem. Soc., Dalton
Trans. 2003, 153.
(28) Bond, E. M.; Englehardt, U.; Deere, T. P.; Rapko, B. M.; Paine, R.
T.; FitzPatrick, J. R. SolVent Extr. Ion Exch. 1997, 15, 381.
(29) Bond, E. M.; Englehardt, U.; Deere, T. P.; Rapko, B. M.; Paine, R.
T.; FitzPatrick, J. R. SolVent Extr. Ion Exch. 1998, 16, 967.
(30) Bond, E. M.; Gan, X.; FitzPatrick, J. R.; Paine, R. T. J. Alloys
Compd. 1998, 271-273, 172.
(34) Reich, H. E.; Levine, R. J. Am. Chem. Soc. 1955, 77, 4913.
(35) Murray, R. J. U.S. Pat. 4,847,301, July 11, 1989.
(36) Wang, J.-W.; Natalie, K. J., Jr.; Nwokogu, G. C.; Pispati, J. S.;
Flaherty, P. T.; Greenwood, T. D.; Wolfe, J. F. J. Org. Chem. 1997, 62,
6152.
(31) Nash, K. L.; Lavallette, C.; Borkowski, M.; Paine, R. T.; Gan, X.
Inorg. Chem. 2002, 41, 5849.
(32) Binyamin, I.; Pailloux, S.; Duesler, E. N.; Rapko, B. M.; Paine, R.
T. Inorg. Chem. 2006, 45, 5886.
(33) Binyamin, I.; Pailloux, S.; Hay, B. P.; Rapko, B. M.; Duesler, E.
N.; Paine, R. T. J. Heterocycl. Chem. 2007, 44, 99.
(37) Bentz, E.; Moloney, M. G.; Westaway, S. M. Tetrahedron Lett. 2004,
45, 7395.
(38) Kurashima, Y.; Miyata, H.; Momose, D. U.S. Pat. No. 4,877,795,
Oct. 31, 1989.
9196 J. Org. Chem., Vol. 72, No. 24, 2007

2-(Pyridin-2-yl)-N,N-diphenylacetamides
SCHEME 1
Ph2NC(O)Cl ) 1/2/2 as shown in Scheme 2. Compounds 3 and
4 are crystalline solids that display (M + H+) ions in ESI-MS
and νco appears at 1682 and 1688 cm-1, respectively, in the IR
spectra. The 1H and 13C{1H} NMR spectra are consistent with
the proposed structures with the methine -C(H)[C(O)NPh2]2
group showing resonances for 3 at δ 5.2 (1H) and δ 60.1 and
for 4 at δ 5.2 (1H) and δ 59.8, respectively. The structure of 4
was further confirmed by single-crystal X-ray diffraction
analysis and a view of the molecule is shown in Figure 2.
It is interesting to compare the chemistry that produces 1-4
against related chemistry that results in formation of derivatives
of the (phosphino)pyridine P-oxides, C.21,22,26,28 In general, using
similar reaction conditions, there seems to be no tendency to
generate bis-phosphine oxide analogues of 3 and 4 with reactant
ratios 2,6-lutidine/Ph2P(O)Cl/BuLi of 1/2/0.1-1. There is a
slight tendency to generate the bis-phosphine oxide with a
combining ratio 1/2/2, but the optimum way to obtain double
substitution is through stepwise formation/isolation of the
monosubstitution product C followed by treatment of it with
BuLi/Ph2P(O)Cl, 1/1.40,41 This suggests that the acidity of the
methylene group separating the pyridine ring from the amide
is greater than that for the methylene group attached to the
phosphine oxide.
coordination complexes. Therefore, we have explored two of
the existing methods for the synthesis of 1. Method 1 utilized
the peptide coupling approach of Kurashima38 and Method 2
involved carbanion substitution with diphenylcarbamoyl chloride
without photostimulation.34
The peptide coupling approach (Method 1) is summarized
in eq 1. Conditions described by Kurashima38 were employed
along with several variations; however, the best yields realized
were only 30-40%. In addition, as is often the case with this
methodology, it was relatively difficult to purify the product.
To further examine this point, deprotonation energies were
computed at the MP2/aug-cc-pVDZ level of theory. The results
are shown in Figure 3. For computational simplicity, the phenyl
groups on the amide nitrogen atom and on the phosphorus atoms
were replaced with methyl groups. Clearly, deprotonations of
both the methylamide and methylphosphine oxide centers on
the pyridine or pyridine oxide rings (eqs 2-7) are significantly
favored over deprotonation of the nonacidic CH4 (eq 8). This
is due to resonance stabilization of the anions in the former.
Then, deprotonation of either the pyridine or pyridine N-oxide-
amides (eqs 2 and 6) is slightly favored over that of the
respective phosphine oxides (eqs 3 and 7). The comparisons of
energetics for eqs 2 and 3 support the experimental observation
described above that the double substitution with formation of
a malonamide is favored over formation of a bis-phosphine
oxide. It is also interesting to note that the computed acidity of
the 6-methyl group is slightly greater for the phosphine oxide
compound compared to that for the amide analogue [eq 4 vs eq
5].
With satisfactory syntheses of 1 and 2 defined, attention was
directed to formation of the respective N-oxide derivatives. Prior
work on 2-(diphenylphosphinomethyl)pyridine P-oxide, C,
indicated that pyridine N-oxidation was easily accomplished in
high yield (>90%), without byproduct formation, by using
m-chloroperbenzoic acid, peracetic acid, or OXONE and it was
anticipated that each of these oxidants would provide a clean
route to the N-oxides of 1 and 2. However, this chemistry is
more complex than expected. With each pyridine precursor 1
and 2 and each oxidant, four products are obtained as sum-
marized in Scheme 3. Since m-chloroperbenzoic acid (mCPBA)
provided the most complete conversions, further discussion is
limited to its use as the oxidant.
Given these shortcomings, a simplified nucleophilic substitu-
tion approach (Method 2) was examined as summarized in
Scheme 1. Initially this reaction was performed in a 1:1 equiv
picolylithium/diphenylcarbamoyl chloride reactant ratio; how-
ever, it was noted that significant amounts of 2-(pyridin-2-yl)-
N,N,N′,N′-tetramethylmalonamide 3 also formed, probably due
to the enhanced acidity of the acetamide, -CH2C(O)NPh2,
protons following formation of 1. Not only was the yield of 1
reduced by formation of the malonamide, but separation of the
two products was difficult. A variety of conditions and reactant
stoichiometries were explored and the optimum yield (83%
based on diphenylcarbamoyl chloride) and purification were
achieved with a 1:0.2 equiv picolylithium:carbamoylchloride
ratio. With this combining ratio, no malonamide byproduct was
produced and 1 was isolated as an analytically pure yellow-
orange crystalline solid. The analogue, 2-(6-methyl-pyridin-2-
yl)-N,N-diphenylamide, 2, was prepared in a similar fashion and
isolated as a yellow solid in 70% yield (based on diphenylcar-
bamoyl chloride).
Both 1 and 2 display an intense (M + H+) ion in ESI-MS
and IR spectra contain an adsorption at 1674 (1) or 1675 cm-1
(2) that are assigned to νco. The 1H and 13C{1H} NMR spectra
for 1 and 2 are consistent with the proposed structures, with
diagnostic resonances for C1 [δ 3.80 (2H); 45.6] and C7 [δ
170.7] in 1 and C1 [δ 3.74 (2H); 45.4], C7 [δ 170.8], and C8 [δ
2.45 (3H); 24.8] in 2. In addition, the molecular structures of 1
and 2 were confirmed by single-crystal X-ray diffraction
analyses and views of the molecules are shown in Figure 1.
As noted above, 2-(pyridin-2-yl)-N,N,N′,N′-tetramethylma-
lonamide 3 also formed in the reaction summarized in Scheme
1 when more than 0.2 equiv of Ph2NC(O)Cl was available.
Indeed, 3 and the related compound 4 were isolated in 80%
yield from a combining ratio of 2-picoline or 2,6-lutidine/BuLi/
Initially, oxidation of 1 with mCPBA was studied with a 1:1
combining ratio in CHCl3 at 23 °C. TLC (ethyl acetate) of
reaction mixtures indicated the formation of at least three
products. This observation led to the study of substrate (1 or
(40) Bodrin, G. V.; Matveeva, A. G.; Terekhova, M. I. IzV. Akad. Nauk
SSSR, Ser. Khim. 1991, 4, 912.
(41) Gan, X.; Paine, R. T. Unpublished results.
(39) The atom numbering system chosen for the X-ray crystal structures
differs from that employed for the NMR assignments.
J. Org. Chem, Vol. 72, No. 24, 2007 9197

Pailloux et al.
FIGURE 1. Molecular structure and atom labeling scheme for 1 and 2.39
SCHEME 3
provided a small amount (1%) of 5 in the first fraction and the
major product 7 (71%) in the second fraction (based on 1). The
column was then eluted with 2% MeOH/CH2Cl2 and 9 (17%)
and 11 (10%) were recovered. Alternatively, a gradient mixture
of MeOH/CH2Cl2 was used to elute the column and similar
product yields were obtained.
FIGURE 2. Molecular structure and atom labeling scheme for 4.39
SCHEME 2
Given these results, two additional excess oxidant combina-
tions were examined. A mixture of 1 (1 equiv) and mCPBA (3
equiv) in CH2Cl2 was refluxed (12 h) and, following workup,
two spots were detected by TLC. Column chromatography with
EtOAc as eluant gave 5 (1-3%) and a mixture of 11 (62%)
and 9 (38%). In a similar manner, 1 (1 equiv) and mCPBA (5
equiv) gave a mixture of 11, 9, and a trace of 5, but here the
recrystallization of the product residue led to recovery of pure
11 (28%) as colorless crystals.
In summary, no conditions were found that led to high yield
formation of the R-ketoamide 5; however, it was isolated as
colorless crystals, in low yield, with the deficient oxidant
condition. Compound 7 was the dominant product when 1.2
equiv of oxidant was employed and it was isolated in pure form.
Compound 9, the most desired ligand target, was not obtained
as a dominant product and it was very difficult to purify.
Compound 11 was dominant when excess oxidant was supplied
and it was isolated in modest yield. Using parallel reaction
conditions, the oxidation of 2 proceeded in a nearly identical
manner to give 6 (minor product), 8 (dominant product with 1
equiv of mCPBA), 10, and 12 (dominant product with 3 equiv
of mCPBA). It is also found that oxidation of pure, isolated
samples of 7 (CH2Cl2, 1.3 equiv of mCPBA, reflux, 12 h)
produced 100% conversion to 11 while identical treatment of
2)/oxidant (mCPBA) combining ratios in the range 0.5-2 and
the discovery that four products are formed in varying amounts.
The details of results from ratios 0.87 and 1.2 are described
since these led to the best product separations.
The combination of 1 (1 eq) with mCPBA (0.87 eq) in
CH2Cl2 at reflux (12 h) gave a mixture that, following workup,
displayed three spots by TLC (ethyl acetate). Subsequent column
chromatography, using EtOAc as the eluant, showed that the
first spot corresponds to 5 and it was isolated in 7% yield (based
on mCPBA). The second fraction from the column initially
contained 7 (45%) with a trace of starting material, and at the
end of this fraction, pure 7 was obtained (19%). The third
fraction was recovered by use of MeOH (2%) in CH2Cl2 as
eluant and this contained 9 (19%). Compound 11 was not
observed under these conditions. With a combining ratio of 1
(1 equiv) with mCPBA (1.2 equiv) in CH2Cl2 at 23 °C (12 h)
three spots were observed in TLC (ethyl acetate) following
workup. Column chromatography with EtOAc as the eluant
9198 J. Org. Chem., Vol. 72, No. 24, 2007

2-(Pyridin-2-yl)-N,N-diphenylacetamides
FIGURE 3. Computed deprotonation reaction energies for model compounds of C and M.
FIGURE 4. Molecular structures and atom labeling schemes for 6 and 7.39
isolated samples of 9 gave 11 but more slowly (66% conversion
Clearly, strong base-promoted substitution chemistry on
in 12 h), and conversion was still incomplete after 24 h.
2-picoline and 2,6-lutidine by N,N-diphenylcarbamoyl chloride
that initially produces 1 and 2 and then 3 and 4, respectively,
and the multichannel chemical oxidation chemistry for 1 and 2
differ from the chemistry involving the phosphine oxide
analogues of C-F.21,26 In the phosphine oxides, double
substitution only occurs under more forcing conditions and
oxidation chemistry results only in formation of N-oxides related
to 9 and 10. As noted above, computational analyses suggest
that the methylene (C1) protons are likely more acidic in 1 and
2 than in the phosphine oxide analogues making the (C1) carbon
more susceptible to the second substitution step or oxidation.
It appears that there is a preference for initial oxidation to occur
at the (C1) carbon atom over the pyridine N atom since, with
reactant ratios [O]:1(2) ) 0.8-1.0, 7(8) is the dominant product.
The N-oxide 9(10) forms under all conditions but in low yield,
while 11(12) results from mixtures rich in oxidant.
Spectroscopic characterization data (IR, NMR, MS) for each
oxidation product 5-12 were collected. Each compound
displays an intense [M + H+] ion and infrared bands for the
1
resident functional groups (CdO, N-O, and/or OH). The H
and 13C{1H} NMR spectra are consistent with the proposed
structures. In addition, molecular structures for 6 and 7 (Figure
4) and for 12 and a mixture of 9 and 11 (Figure 5) were
determined by X-ray diffraction techniques. As mentioned
earlier, it is difficult to separate 9 and 11 and mixed crystals
were typically obtained. In fact, the structure refinement for the
mixed crystal was better behaved than that for the pure
components and this is likely a result of more favorable packing
even though no classical intermolecular hydrogen bonding is
apparent. In all cases the crystal structures confirm the
spectroscopically assigned structures.
J. Org. Chem, Vol. 72, No. 24, 2007 9199

Pailloux et al.
FIGURE 5. Molecular structures and atom labeling schemes for a mixture of 9 + 11 and 12.39
only the N-oxidation products 13 and 14 are formed and there
is no evidence for hydroxylation of the C1 carbon. Compounds
13 and 14 were characterized by IR, MS, and NMR spectros-
copy, and the molecular structure of 14 was confirmed by X-ray
crystallography (Figure 6). The process by which the R-ketoa-
mides 5 and 6 form is less clear, but they are always very minor
products and therefore may result from an impurity oxidant.
However, it has been previously noted that mandelamides,
p-RC6H4-C(H)(OH)-C(O)N(H)R′, undergo oxidation with
BaMnO4 to give glyoxamides, p-RC6H4C(O)C(O)N(H)R′.49 This
supports the conclusion that 5(6) results from oxidation of
initially formed 7(8).
FIGURE 6. Molecular structure and atom labeling scheme for 14.39
It is noted that N,N-dialkyl-2-pyridyl glyoxyl amides, alkyl-
amido analogues of the R-ketoamide 5, have been previously
reported to be difficult to prepare.42 The N,N-diethyl derivative
is reported as a product of (a) SeO2 induced ring opening of
3-N,N-diethylacetamido triazolopyridine,43 (b) Pd-catalyzed
R-ketoamido carbonylation of 2-iodopyridine,44-47 and (c) a
combination 2-pyridyl esters and amino acetonitrile followed
by oxidation of the intermediate cyanoketone with bleach.48 The
last approach was also used to prepare a n-Pr analogue, but no
examples of N,N-diaryl amide derivatives are reported. In
addition, Jones43 briefly described formation of N,N-diethyl-2-
pyridyl glycolamide, an alkyl amido analogue of 7, from acidic
hydrolysis of its triazolopyridine precursor.
Conclusion
This study has defined high-yield syntheses for 2-(pyridin-
2-yl)-N,N-diphenylamides and 2-(pyridin-2-yl)-N,N,N′,N′-tet-
raphenylmalonamides. The chemical N-oxidation chemistry for
the latter, 3 and 4, is straightforward producing the trifunctional
molecules 13 and 14 in high yields. The chemical N-oxidation
chemistry of the former, 1 and 2, is more complex, but the
products have been identified and characterized. Compounds
1, 2, 9, and 10 have the potential to act as bidentate bifunctional
chelating ligands while trifunctional 3-8 and 11-14 may serve
as tridentate ligands. From the ligand design perspective, optimal
ligand architectures would adopt low-energy conformations in
which all the binding sites are oriented to complement the metal
ion. However, without exception the molecular structures
obtained for these ligands reveal that the oxygen-bearing
functional groups are rotated away from each other in the
crystals placing the binding sites in a divergent rather than
convergent orientation. Similar behavior observed in prior
studies of phosphine oxide analogues has been attributed to
minimizing dipole/electron pair repulsions.21,26,41 To the extent
that conformations observed in the solid state correspond to
those present in solution, these results suggest that structural
Further evidence that 7 and 8 are the key initial products in
the oxidation processes for 1 and 2 is found in the outcome of
the oxidation of the malonamides 3 and 4. As shown in eq 9,
(42) Abarca, A.; Gomez-Aldaravi, E.; Jones, G.; Sliskovic, D. R. J. Chem.
Res. (S) 1983, 144, 1341.
(43) Jones, G.; Mouat, D. J.; Tonkinson, D. J. J. Chem. Soc., Perkin
Trans. 1985, 2719.
(44) Couve-Bonnaire, S.; Carpentier, J.-F.; Mortreux, A.; Castanet, Y.
AdV. Synth. Catal. 2001, 343, 289.
(45) Couve-Bonnaire, S.; Carpentier, J.-F.; Castanet, Y.; Mortreux, A.
Tetrahedron Lett. 1999, 40, 3717.
(46) Tsukada, N.; Ohba, Y.; Inoue, Y. J. Organomet. Chem. 2003, 687,
436.
(47) Ozawa, F.; Sugimoto, T.; Yuasa, Y.; Santra, M.; Yamamoto, T.;
Yamamoto, A. Organometallics 1984, 3, 683.
(48) Yang, Z.; Zhang, Z.; Meanwell, N. A.; Kadow, J. F.; Wang, T.
Org. Lett. 2002, 4, 1103.
(49) Haddadin, M. J.; Tannus, H. T. Heterocycles 1984, 22, 773.
9200 J. Org. Chem., Vol. 72, No. 24, 2007

2-(Pyridin-2-yl)-N,N-diphenylacetamides
1H). 13C{1H} (62.5 MHz, CDCl3): δ 24.8, 45.4, 121.3, 121.6,
126.9, 128.1, 129.1, 136.9, 143.2, 155.3, 158.2, 168.2, 170.8. IR
(KBr, cm-1): 1675 (νco). HRMS: found 303.1432 (M + H+).
C20H19N2O requires 303.1497. Anal. Calcd for C20H18N2O: C 79.44,
H 6.00, N 9.26. Found: C 78.33, H 5.89, N 9.15.
reorganization will be required to achieve conformations that
allow all binding sites to engage the metal ion. Further studies
are now in progress to investigate the coordination chemistry
for this new family of ligands.
2-(Pyridin-2-yl)-N,N,N′,N′-tetraphenylmalonamide (3). n-BuLi
solution (1.6 M in THF, 7.5 mL, 12 mmol) was added dropwise to
picoline (1.0 g, 12 mmol), then diluted in dry THF (10 mL) and
held at 0 °C. The mixture was stirred, then warmed to 23 °C (1 h)
and chilled again to 0 °C. Diphenylcarbamoyl chloride (5.57 g, 24
mmol) in dry THF (15 mL) was added dropwise with stirring and
the mixture was heated overnight (50 °C). The mixture was then
concentrated and the residue was hydrolyzed with water (50 mL)
and extracted with CH2Cl2 (3 × 50 mL). The combined organic
phases were dried over MgSO4, and the residue was flash
chromatographed (silica gel) with EtOAc as eluant. The solvent
was removed and a yellow solid (3) was obtained (4.1 g, 80%).
This was crystallized from MeOH to afford tan crystals. Yield: 3.0
g, 57%. Mp 120-124 °C. 1H NMR (250 MHz, CDCl3): δ 5.22 (s,
1H), 6.75 (d, J ) 7.1 Hz, 4H), 7.13 (4H), 7.25-7.30 (13H), 7.45
(d, J ) 7.8 Hz, 1H), 7.63 (td, J ) 6.0, 1.7 Hz, 1H), 8.33 (d, J )
4.2 Hz, 1H). 13C{1H} NMR (62.5 MHz, CDCl3): δ 60.1, 122.2,
124.4, 125.2, 126.2, 128.1, 128.8, 129.4, 129.6, 136.1, 141.8, 142.4,
148.7, 154.5, 167.6. IR (KBr, cm-1): 1682 (νco). HRMS: found
484.1989 (M + H+). C32H26N3O2 requires 484.2025.
Experimental Section
2-(Pyridin-2-yl)-N,N-diphenylacetamide (1): Method 1. 1,3-
Dicyclohexylcarbodiimide (DCC) (3.2 g, 0.015 mol) was added to
a mixture of 2-pyridyl acetic acid hydrochloride (2.065 g, 0.012
mol), diphenylamine (2.03 g, 0.012 mol), and 1-hydroxybenzo-
triazole hydrate (HOBT) (1.6 g, 0.012 mol) in dry pyridine (25
mL) and the mixture was stirred (23 °C, 18 h). The DCU formed
was removed by filtration, the filtrate was evaporated, and the oily
residue was treated with aqueous HCl (1 N, 50 mL). The aqueous
phase was washed with Et2O (3 × 25 mL) and then treated with
aqueous NaOH solution (2 N) to pH 11. This solution was extracted
with CH2Cl2 (100 mL) and the organic phase dried over Na2CO3.
The volatiles were vacuum evaporated leaving a yellow oil, 1.
Yield: 1.3 g (37%). Chromatographic column purification was
performed with silica gel 70-230 mesh and CH2Cl2:MeOH 100:3
1
as eluant. H NMR (250 MHz, CDCl3): δ 3.79 (2H), 7.06 (d,d, J
) 7.2 Hz, 1H), 7.20 (d,d, J ) 7.3 Hz, 1H), 7.20-7.40 (m, 10H),
7.54 (d, d, J ) 1.8, 7.7 Hz, 1H), 8.45 (d, J ) 4.8 Hz, 1H). 13C{1H}
NMR (62.5 Hz, CDCl3): δ 45.6, 122.3, 124.7, 127.1, 129.8, 136.9,
143.4, 149.9, 156.4, 170.7. IR (KBr, cm-1): 1674 (νco). MS
(FAB+): m/z 289.1 (M + H+, 35%). Anal. Calcd for C19H16N2O:
C 79.14, H 5.59, N 9.71. Found: C 78.60, H 5.82, N 9.33.
2-(6-Methylpyridin-2-yl)-N,N,N′,N′-tetraphenylmalonamide
(4). n-BuLi solution (1.6 M in THF, 11.6 mL, 18 mmol) was added
dropwise to 2,6-lutidine (1.0 g, 9.3 mmol) in dry THF (15 mL) at
0 °C. The stirred mixture turned red and was then warmed to
23 °C (30 min). The resulting mixture was cooled to 0 °C and
diphenylcarbamoyl chloride (4.32 g, 18.6 mmol) in dry THF (15
mL) was added dropwise with stirring. The solution turned red and
was stirred overnight (50 °C). Solvent was then vacuum evaporated
and the residue was treated with CH2Cl2/H2O (50 mL/50 mL), the
phases separated, and the aqueous phase extracted with CH2Cl2 (3
× 50 mL). The combined organic phases were dried (MgSO4) and
concentrated and the residue was flash chromatographed with
EtOAc/hexane (1/1) as the initial eluant. During elution, the percent
of EtOAc was increased to 100%. The solvent was evaporated and
a colorless solid (4) was obtained. Yield: 3.68 g, 80%. Mp 150-
Method 2. 2-Picoline (2 g, 21 mmol) in dry THF (15 mL) was
treated dropwise with n-BuLi (13 mL, 1.6 M in THF, 21 mmol) at
0 °C. Following addition, the mixture was warmed to 23 °C and
stirred (1 h). The resulting mixture was cooled (0 °C) and
diphenylcarbamoyl chloride (0.99 g, 4.3 mmol) in THF (15 mL)
was added dropwise. This mixture was stirred overnight (23 °C).
The solvent was evaporated and the remaining residue carefully
hydrolyzed (50 mL). The aqueous phase was extracted with
CH2Cl2 (3 × 50 mL) and the organic phase was washed with water
(50 mL) and dried over MgSO4. The solvent was vacuum
evaporated leaving a red oil. Chromatographic column purification
was performed with silica gel 70-230 mesh and ethyl acetate or
CH2Cl2:MeOH 99:1, then 98/2 as eluant. Solvent was evaporated
leaving a yellow-orange solid, 1. Yield: 0.79 g, 81%. Subsequent
washing with hexane (2 × 10 mL) left a white solid (0.57 g, 59%).
1H NMR (CDCl3): δ 3.83 (s, 2H), 7.00 (d, J ) 6.8 Hz, 1H), 7.15-
7.45 (m, 11H), 7.55 (d,d, J ) 2, 7.8 Hz, 1H), 8.50 (dd, J ) 0.75,
4.0 Hz, 1H). 13C{1H} NMR (62.5 MHz, CDCl3): δ 44.9, 121.6,
124.0, 126.5, 129.2, 136.2, 142.7, 149.2, 155.7, 170.0. HRMS:
found 289.1330 (M + H+). C19H17N2O requires 289.1341. Anal.
Calcd for C19H16N2O: C 79.14, H 5.59, N 9.72. Found: C 78.87,
H 5.59, N 9.70.
2-(6-Methyl-pyridin-2-yl)-N,N-diphenylacetamide (2). n-BuLi
solution (1.6 M in THF, 11.7 mL) was added dropwise to a stirred
solution of 2,6-lutidine (2 g, 19 mmol) in dry THF (15 mL) at
0 °C. The mixture turned red and after stirring (30 min, 23 °C)
diphenylcarbamoyl chloride (0.88 g, 3.8 mmol) in dry THF (15
mL) was added dropwise at 0 °C. The solution color turned yellow
and stirring was continued overnight (23 °C). Solvent was vacuum
evaporated and the residue was treated with a CH2Cl2 (50 mL)/
H2O (50 mL) mixture. The aqueous phase was extracted with
CH2Cl2 (3 × 50 mL) and the combined organic phases were dried
over MgSO4 and concentrated. The residue was flash chromato-
graphed (silica gel) with EtOAc/hexane (3/7) as initial eluant. The
amount of EtOAc was increased until the final eluant contained
only EtOAc. The solvent was evaporated, the residue was recrystal-
lized from MeOH (-20 °C), and a yellow solid, 2, collected.
Yield: 0.80 g, 70%. Mp 98-100 °C. 1H NMR (500 MHz,
CDCl3): δ 2.45 (s, 3H), 3.74 (s, 2H), 6.93 (d, J ) 7.5 Hz, 1H),
6.98 (d, J ) 6.9 Hz, 1H), 7.25 (m, 10H), 7.40 (d, d, J ) 7.5 Hz,
1
152 °C. The solid was recrystallized from MeOH. H NMR (250
MHz, CDCl3): δ 2.4 (s, 3H), 5.2 (s, 1H), 6.8-7.5 (m, 23H).
13C{1H} NMR (62.5 MHz, CDCl3): δ 23.9, 59.8, 121.0, 121.2,
125.8, 126.0, 127.6, 128.4, 129.2, 135.9, 141.7, 142.4, 153.5, 157.1,
167.7. IR (KBr, cm-1): 1688 (νco). HRMS: found 498.2163
(major), 499.2257 (minor) (M + H+). C33H28N3O2 requires
498.2182. Anal. Calcd for C33H27N3O2: C 79.66, H 5.47, N 8.44.
Found: C 79.48, H 5.36, N 8.40.
2(1-Oxypyridin-2-yl)-N,N,N′,N′-tetraphenylmalonamide (13).
A sample of 3 (0.4 g, 0.8 mmol) in CH2Cl2 (5 mL) was combined
with m-CPBA (0.185 g, 1.07 mmol) and the mixture was refluxed
overnight with periodic TLC monitoring of the reaction progress
(CH2Cl2/MeOH, 99/1). The resulting mixture was quenched (sat.
NaHCO3, 3 × 10 mL) and the aqueous phase was extracted with
CH2Cl2 (3 × 10 mL). The organic phase was dried (MgSO4) and
concentrated and the residue was purified by flash chromatography
with a gradient of MeOH in CH2Cl2. The product 13 was isolated
1
as a white solid. Yield: 0.9 g, 88%. Mp 134-136 °C. H NMR
(250 MHz, CDCl3): δ 6.0 (s, 1H), 6.8 (d, J ) 7.0 Hz, 4H), 7.2 (m,
4H), 7.2-7.4 (m, 14H), 7.7 (dd, J ) 7.0, 2.0 Hz, 1H), 8.0 (d, J )
6.5 Hz, 1H). 13C{1H} (62.5 MHz, CDCl3): δ 52.3, 125.2, 125.5,
126.5, 126.8, 127.4, 128.7, 129.3, 129.4, 130.2, 138.9, 141.9, 142.7,
146.8, 166.7. IR (KBr, cm-1): 1681 (νco). HRMS: found 500.1949
(M + H+). C32H26N3O3 requires 500.1974.
2-(6-Methyl-1-oxypyridin-2-yl)-N,N,N′,N′-tetraphenylmalona-
mide (14). A sample of 4 (0.6 g, 1.2 mmol) in MeOH/CH2Cl2 (15
mL/5 mL) was combined with OXONE (0.81 g, 1.32 mmol)
and NaHCO3 (0.21 g, 2.5 mmol) and refluxed (12 h). Solvent
was evaporated and the residue was treated with CH2Cl2/H2O (50
J. Org. Chem, Vol. 72, No. 24, 2007 9201

Pailloux et al.
mL/50 mL). The aqueous phase was separated and extracted with
CH2Cl2 (3 × 10 mL) and the combined organic phases were dried
over MgSO4. The filtered organic phase was evaporated leaving a
white solid that was further purified by column chromatography
with EtOAc/hexane (1:1) as initial eluant followed by pure EtOAc.
The N-oxide 14 was isolated as a white solid. Yield: 0.31 g, 50%.
Mp 164-166 °C. 1H NMR (500 MHz, DMSO-d6): δ 2.77 (s, 3H),
6.17 (s, 1H), 7.35 (s, 4H), 7.80 (m, 6H), 7.90 (m, 9H), 8.00 (d, J
) 7.0 Hz, 2H), 8.12 (d, J ) 7.0 Hz, 2H). 13C{1H} (62.5 MHz,
DMSO-d6): δ 17.7, 52.4, 124.3, 124.6, 125.7, 126.7, 128.3, 128.7,
129.2, 130.0, 141.5, 142.7, 145.3, 147.5, 166.28. IR (KBr, cm-1):
1681 (νco). HRMS: found 514.2130 (M + H+). C33H28N3O3
requires 514.2131. Solubility: CH2Cl2 (v. sol.), MeOH (sol.),
EtOAc (sol.), hexane (insol.).
General Oxidation Procedure. A sample of 1 or 2 (1 equiv)
was dissolved in CH2Cl2 (10 mL) and m-chloroperbenzoic acid
(0.8-5 equiv) was added with stirring. The mixture was then
refluxed overnight. The resulting mixture was quenched with
aqueous saturated NaHCO3 solution and the aqueous phase was
extracted with CH2Cl2. Three spots were typically observed by TLC
and the CH2Cl2 solution containing the products was chromato-
graphed on silica gel (4 cm × 30 cm) with ethyl acetate as the
eluant. Variations in the oxidation and purification procedures led
to optimized yields for 5, 7, 9, and 11 from 1 and 6, 8, 10, and 12
from 2. Details of these procedures are presented in the Supporting
Information.
124.2, 124.7, 125.0, 126.7-129.5, 142.6, 146.8, 148.6, 168.1.
HRMS: found 319.1443 (M + H+). C20H19N2O2 requires 319.1447.
2-Hydroxy-2-(1-oxypyridin-2-yl)-N,N-diphenylacetamide (11).
1H NMR (250 MHz, CDCl3): δ 4.8 (s, 1H), 5.30 (s, 1H), 7.00 (d,
J ) 5.7 Hz, 1H), 7.05 (t, J ) 6.7 Hz, 1H), 7.10 (t, J ) 7.2 Hz,
1H), 7.15-7.40 (m, 10 H), 8.12 (d, J ) 6.0 Hz, 1H). 13C{1H} NMR
(62.5 MHz, DMSO-d6): δ 67.5, 123.9, 124.7, 125.1, 126.9, 127.5,
128.8, 138.2, 142.9, 150.9, 168.6. HRMS: found 321.1213 (M +
H+). C19H17N2O3 requires 321.1239.
2-Hydroxy-2-(6-methyl-1-oxypyridin-2-yl)-N,N-diphenylace-
tamide (12). 1H NMR (250 MHz, CDCl3): δ 2.38 (s, 3H), 5.28 (s,
1H), 6.75 (d, J ) 7.8 Hz, 1H), 6.85 (t, J ) 7.8 Hz, 1H), 7.10 (d,
J ) 8.0 Hz, 1H), 7.15-7.50 (m, 10H). 13C{1H} NMR (62.5 MHz,
CDCl3): δ 17.6, 61.9, 123.5, 124.5, 125.1, 125-130, 148.1, 149.0,
170.0. HRMS: found 335.1389 (M + H+). C20H18N2O3 requires
335.1396.
Electronic Structure Calculations. The energy change for the
gas-phase reaction AH f A- + H+ provides a measure of the
intrinsic acidity of the AH proton. ∆E values, E(A-) + E(H+) -
E(AH), were calculated for selected model compounds with the
NWChem program,50 using second-order Mo¨ller-Plesset perturba-
tion theory (MP2).51 Calculations were performed with the cor-
relation consistent aug-cc-pVDZ basis set,52 including all electrons
in the correlation treatment.
Acknowledgment is made to the U.S. Department of Energy
(DOE), Chemical Sciences, Geosciences and Biosciences Office,
Office of Basic Energy Sciences (Grant DE-FG02-03ER15419)
for financial support of this work (R.T.P.) and the DOE,
Environmental Management Science Program, Office of Science
(73759) (B.P.H.). Calculations were performed with the Mo-
lecular Science Computing Facility (MSCF) in the William R.
Wiley Environmental Molecular Sciences Laboratory, a national
scientific user facility sponsored by the DOE’s Office of
Biological and Environmental Research. We thank Dr. S.-J. Kim
for his initial experimental contributions to this study.
Selected Characterization Data for Oxidation Products:
2-Oxo-N,N-diphenyl-2-(pyridin-2-yl)acetamide (5). 1H NMR (250
MHz, CDCl3): δ 7.10-7.50 (m, 11H), 7.65-7.85 (m, 2H), 8.75
(d,d, J ) 4.0, 0.8 Hz, 1H). 13C{1H} NMR (62.5 MHz, CDCl3): δ
123.7, 126.4, 127.3, 128.3, 128.8, 129.5, 129.6, 130.0, 137.5, 140.8,
141.6, 150.2, 151.9, 167.8, 191.0. HRMS: found 303.1099 (M +
H+). C19H15N2O2 requires 303.1134.
2-Oxo-N,N-diphenyl-2-(6-methylpyridin-2-yl)acetamide (6).
1H NMR (250 MHz, CDCl3): δ 2.15 (s, 3H), 6.70-7.30 (m, 13H).
13C{1H} NMR (62.5 MHz, CDCl3): δ 24.2, 120.0, 125.8, 126.6,
127.2, 127.9, 128.8, 128.9, 129.1, 136.8, 140.2, 141.1, 150.6, 158.4,
167.5, 190.8. HRMS: found 317.1264 (M + H+). C20H17N2O2
requires 317.1290.
Supporting Information Available: Experimental details for
the formation and characterization of 4-11, detailed data from the
X-ray crystallographic structure determinations, and crystallographic
information (CIF). This material is available free of charge via the
Internet at http://pubs.acs.org.
1
2-Hydroxy-N,N-dphenyl-2-(pyridin-2-yl)acaetamide (7). H
NMR (250 MHz, CDCl3): δ 4.65 (s, 1H), 5.35 (s, 1H), 6.80 (d, J
) 8.6 Hz, 1H), 6.95 (s, 1H), 7.10 (d,d, J ) 4.0, 1.1 Hz, 1H), 7.2-
7.4 (m, 9H), 7.45 (d,d, J ) 7.8, 1.8 Hz, 1H), 8.50 (m, J ) 4.8, J
) 2.6, 1.8, J ) 0.9 Hz, 1H). 13C{1H} NMR (62.5 MHz, CDCl3):
δ 73.3, 122.9, 123.3, 128.4, 128.6, 129.4, 137.0, 150.0, 158.0, 172.6.
HRMS: found 305.1292 (M + H+). C19H17N2O2 requires 305.1290.
2-Hydroxy-N,N-diphenyl-2-(6-methylpyridin-2-yl)aceta-
JO701408Y
(50) (a) Straatsma, T. P.; Apra`, E.; Windus, T. L.; Bylaska, E. J.; de
Jong, W.; Hirata, S.; Valiev, M.; Hackler, M. T.; Pollack, L.; Harrison, R.
J.; Dupuis, M.; Smith, D. M. A.; Nieplocha, J.; Tipparaju, V.; Krishnan,
M.; Auer, A. A.; Brown, E.; Cisneros, G.; Fann, G. I.; Fruchtl, H.; Garza,
J.; Hirao, K.; Kendall, R.; Nichols, J.; Tsemekhman, K.; Wolinski, K.;
Anchell, J.; Bernholdt, D.; Borowski, P.; Clark, T.; Clerc, D.; Dachsel, H.;
Deegan, M.; Dyall, K.; Elwood, D.; Glendening, E.; Gutowski, M.; Hess,
A.; Jaffe, J.; Johnson, B.; Ju, J.; Kobayashi, R.; Kutteh, R.; Lin, Z.;
Littlefield, R.; Long, X.; Meng, B.; Nakajima, T.; Niu, S.; Rosing, M.;
Sandrone, G.; Stave, M.; Taylor, H.; Thomas, G.; van Lenthe, J.; Wong,
A.; Zhang, Z. NWChem, A Computational Chemistry Package for Parallel
Computers, Version 4.6; Pacific Northwest National Laboratory: Richland,
WA, 2004. (b) Kendall, R. A.; Apra`, E.; Bernholdt, D. E.; Bylaska, E. J.;
Dupuis, M.; Fann, G. I.; Harrison, R. J.; Ju, J.; Nichols, J. A.; Nieplocha,
J.; Straatsma, T. P.; Windus, T. L.; Wong, A. T. Comput. Phys. Commun.
2000, 128, 260-283.
1
mide (8). H NMR (250 MHz, CDCl3): δ 2.50 (s, 3H), 5.40 (s,
1H), 6.75 (d, J ) 7.7 Hz, 1H), 7.00 (d, J ) 7.7 Hz, 1H), 7.10-
7.35 (m, 10H), 7.4 (d, d, J ) 7.7 Hz, 1H), 13C{1H} NMR (62.5
MHz, CDCl3): δ 24.2, 73.0, 119.1, 122.4, 127.6-130.1, 136.8,
157.2, 158.0, 172.5. HRMS: found 319.1446 [M + H+]. C20H19N2O2
requires 319.1447.
2-(1-Oxy-pyridin-2-yl)-N,N-diphenylacetamide (9). 1H NMR
(250 MHz, CDCl3): δ 3.80 (s, 2H), 7.15-7.50 (m, 13H), 8.25 (d,
d, J ) 7.5, 4.2 Hz, 1H). 13C{1H} NMR (62.5 MHz, CDCl3): δ
37.9, 124.2, 125.0, 126.1, 127.3, 127.7, 128.4, 129.4, 138.8, 142.4,
147.0, 167.7. HRMS: found 305.1291 (M + H+). C19H17N2O2
requires 305.1290.
2-(6-Methyl-1-oxypyridin-2-yl)-N,N-diphenylacetamide (10).
1H NMR (250 MHz, CDCl3): δ 2.50 (s, 3H), 3.80 (s, 2H), 6.80-
7.60 (m, 13H). 13C{1H} NMR (62.5 MHz, CDCl3): δ 18.0, 38.6,
(51) Moller, C.; Plesset, M. S. Phys. ReV. 1934, 46, 618.
(52) (a) Dunning, T. H., Jr. J. Chem. Phys. 1989, 90, 1007. (b) Kendall,
R. A.; Dunning, T. H., Jr.; Harrison, R. J. J. Chem. Phys. 1992, 96, 6796.
9202 J. Org. Chem., Vol. 72, No. 24, 2007