Preparation of substituted 1,2-dihydro-3H-pyrazol-3-ones from polylithiated 2′-phenylphenylacetohydrazides and aromatic esters

Article abstract of DOI:10.1002/jhet.5570380326

Several 2′-phenylphenylacetohydrazides were polylithiated with excess lithium diisopropylamide, and the resulting intermediates were condensed with several aromatic esters to afford C-acylated intermediates that were not usually isolated, but acid cyclize

Full text of DOI:10.1002/jhet.5570380326

May-Jun 2001
Preparation of Substituted 1,2-Dihydro-3H-pyrazol-3-ones from
695
Polylithiated 2'-Phenylphenylacetohydrazides and Aromatic Esters
Jennifer R. Downs, Stefan J. Pastine, Jessica D. Townsend, Heather A. Greer,
Wayne Kelley, Jr., Deborah A. Schady, Teresa Lentz McConaughy,
Clyde R. Metz, and Charles F. Beam*
Department of Chemistry and Biochemistry, College of Charleston, Charleston, SC 29424
Catharine D. Almquist
Department of Physical Sciences, Trident Technical College, Charleston, SC 29423
William T. Pennington and Rosa D. Bailey Walsch
Department of Chemistry, Clemson University, Clemson, SC 29634
Received July 25, 2000
Dedicated to the Memory of Raymond N. Castle
Several 2'-phenylphenylacetohydrazides were polylithiated with excess lithium diisopropylamide, and the
resulting intermediates were condensed with several aromatic esters to afford C-acylated intermediates that
were not usually isolated, but acid cyclized directly to 1,4,5-trisubstituted, 1,2-dihydro-3H-pyrazol-3-ones.
J. Heterocyclic Chem., 38, 695 (2001).
While the preparations, reactions, and uses of 1H-pyra-
excess lithium diisopropylamide, and condensed-cyclized
the polylithiated intermediates with a variety of aromatic
esters. This was followed by acid cyclization of the
C-acylated intermediates to afford isocarbostyrils (1(2H)-
isoquinolinones) [26].
One of our major strong-base multiple anion synthesis
efforts has dealt with the preparation of 1H-pyrazoles and
related compounds by the utilization of C(α), N-hydrazone
(e.g., phenyl, benzoyl, carboalkoxy, etc.) entry compounds
that were polylithiated with excess lithium diisopropylamide
[27-41]. The polylithiated intermediates were condensed
with a variety of esters and other electrophilic reagents, fol-
lowed by an acid cyclization of C-acylated intermediates that
were not usually isolated. This resulted in an unequivocal
synthesis of a single pyrazole isomer, especially unsymmetri-
cal 3,5-disubstituted, in good yields, that could be easily
purified by recrystallization from common solvents.
zoles and related heterocyclic compounds are well docu-
mented [1], investigations involving other pyrazole com-
pounds such as 1,2-dihydro-3H-pyrazol-3-ones [2,3] have
received less investigative attention. For example, a key
compound to this report, 1,2-dihydro-1,4,5-triphenyl-3H-
pyrazol-3-one 4, has been prepared by: (1) the fusion of
2'-phenylacetohydrazine with ethyl 2-benzoyl-2-phenylac-
etate [4]; or (2) by the condensation of benzoylphenyl
ketene with phenylhydrazine [5]; or (3) by the reaction of
diphenylcyclopropenone with excess phenylhydrazine [6].
Several additional and related alkyl, or alkyl-aryl, 1,4,5-
trisubstituted, 1,2-dihydro-3H-pyrazol-3-ones have also
been prepared and studied, especially with regard to their
biological-health applications or use in other syntheses [7-
15]. There is a preference to listing the structures for these
molecules as 1,2-dihydro-3H-pyrazol-3-ones instead of
their tautomers, 3-hydroxy-1H-pyrazoles. Both forms
have been reported by investigators [4-19], which may
indicate the differences that exist when the supporting
structural data was obtained from a solution, a mull, or a
crystalline form of a particular compound.
The focus of this introductory study has been to polylithi-
ate several 2'-phenylphenylacetohydrazides 1-3 with excess
lithium diisopropylamide, C-acylate the polylithated inter-
mediates (presumed trilithiation, see Scheme) [42] with a
variety of benzoate esters, followed by acid cyclization to
the targeted dihydropyrazolones 4-13. Initially, polylithi-
ated phenylhydrazide 1 was condensed-cyclized with
methyl benzoate to afford dihydropyrazolone 4 in an 83%
yield (mp 283-285°; lit mp 282° [6]). The yield of other
compounds prepared, 5-13, ranged from 52-97%, and they
Compound 1, 2'-phenylphenylacetohydrazide, a key
starting material used during this study, has been used for
the preparation of other pyrazole or pyrazole-related hetero-
cyclic compounds such as methods involving variously sub-
stituted N-methyl or N-acylphenylacetohydrazides, or a con-
densation-cyclization of a probable carbanion resulting from
deprotonation with calcium hydride followed by the addi-
tion of N,N-dimethylformamide [20-25].
1
13
were characterized by H and C nuclear magnetic reso-
nance spectra, with support from combustion analysis for
C, H, and N. It was possible to isolate a C-acylated prod-
uct, as evidenced from the condensation of polylithiated
acid hydrazide (from 1) with methyl 3,4,5-trimethoxyben-
zoate to afford β-ketohydrazide 10a in a 76 % yield.
In recent investigations with other carbohydrazides, we
polylithiated o-toluoylcarboalkoxyhydrazides (2'-(2-
methylbenzoyl)hydrazinocarboxylic acid esters) with

696
Vol. 38
J. R. Downs, S. J. Pastine, J. D. Townsend, H. A. Greer, W. Kelley, Jr., D. A. Schady, T. L. McConaughy,
C. R. Metz, C. F. Beam, C. D. Almquist, W. T. Pennington and R. D. Bailey Walsch
The molecular structure of 8, C H N O (unsolvated)
21 16
2 2
is shown in Figure 1, atomic positional parameters are
listed in Table 2, and selected bond distances and angles
are listed in Table 3.
Each of the rings is essentially planar with a mean devi-
ation from each respective least squares best plane of
0.0045 Å for the heterocylic ring, 0.0075 Å for C4-C9,
0.0057 Å for C10-C15, and 0.0054 Å for C16-C21. The
least squares best planes representing the three phenyl
groups are somewhat perpendicular to the heterocyclic
ring with angles of 141.30° for C4-C9, 108.15° for C10-
C15, and 135.44° for C16-C21.
The crystal packing is dominated by hydrogen bonding.
1
Molecules related by inversion symmetry (at ( / , 0, 1)) are
2
…
linked into dimers through O-H N interactions involving
the pyrazole nitrogen atom and the exocyclic hydroxyl
…
…
…
group (O1 N1' 2.747(3) Å; H1 N1' 1.83 Å; O1-H1 N1'
175°). Dimers related by inversion symmetry (at (0, 0,
1
/ )) are linked together through bridges involving t-butyl
2
alcohol solvent molecules, involving the hydroxyl groups
of the solvent and of the phenol ring of the molecule. The
bridging interactions are asymmetric, with one pair of
…
…
short interactions (O2 O3'' 2.685(3) Å; H2 O3'' 1.76 Å;
…
O2-H2 O3'' 168°) and one pair of long interactions
…
…
…
(O3 O2 2.985(3) Å; H26 O2 2.08 Å; O3-H26 O2
152°). The two sets of hydrogen bonding interactions
result in the molecules being linked into infinite chains
running parallel to the ac-diagonal of the unit cell (see
Figure 2). There are no significant interchain interactions
involved in the packing of the chains to complete the struc-
ture (see Figure 3).
Since infrared spectra of compounds 4-13 did not give con-
sistent or convincing carbonyl or hydroxyl absorptions [43],
1
and H nmr spectra of compounds 4 and 6 did not display
NH/OH absorptions, an X-ray crystal structure of dihydro-
pyrazolone 8 (X = H and R = 2-hydroxyphenyl) [44] was
5
obtained. Surprisingly, good crystals for this analysis were
obtained from tert-butyl alcohol, and the overall structure was
found in the 3-hydroxy-1H-pyrazole form.
Figure 2. Chain formation resulting from H-bonding between Pyrazole,
N- and exocyclic hydroxyl group and between phenol hydroxyl groups of
bridging tert-butyl alcohol molecules.
1
The H nuclear magnetic resonance spectra of 4-13 were
satisfactory for identifying aromatic protons, and those
associated with a functional group such as ArOCH in 5, 9,
3
10 and 12, δ 3.46-3.86 ppm; the ArCH in 7, δ 2.27 ppm,
3
13
or the tert-butyl-Ar in 11, δ 1.24 ppm. The C nuclear
magnetic resonance absorptions for the aromatic carbons
and functional group carbons were routine, and some of
the heterocyclic ring carbons were identified as follows:
Figure 1. ORTEP diagram (50% ellipsoids for non-hydrogen atoms) for
8, C
H N O .
21 16 2 2

May-Jun 2001
Preparation of Substituted 1,2-Dihydro-3H-pyrazol-3-ones
697
Table 1
Crystallographic Data for 8, C
.
H
N O C H O
2 2 4 10
21 16
Crystal Dimensions (mm)
Space Group
0.30 x 0.30 x 0.30
P-1 (#2)
7.143(3)
12.078(7)
14.220(5)
99.06(2)°
103.13(1)°
101.68(2)°
1143.2(9)
402.49
a (Å)
b (Å)
c (Å)
α
β
γ
3
V (Å )
fw
Z
2
1.17
3
d
(g/cm )
calc
λ(Å)
0.71069
0.77
-1
µ (cm )
R [a]
0.062
R
[b]
0.069
w
Goodness of Fit
1.86
2
2
1/2
[a] R = Σ(|F | - |F | )/Σ |F |, [b] R = {Σ[w(|F | - |F | ) ]/Σ(w|F | )}
o
c
o
w
o
c
o
Figure 3. Packing of infinite chains.
Table 2
Atomic Positional Parameters for 8, C
H
N O •C H
O
21 16
2
2
4
10
C-3 δ 159.0-159.8 ppm; C-4 δ 105.4-110.1 ppm; C-5 was
not distinguished from other aromatic carbon absorptions.
The yields of dihydropyrazolones 4-13 may not be
optimal, especially for a particular compound, but the cur-
rent general procedure readily affords multi-gram quanti-
ties of pure products resulting from recrystallization from
common solvents. They are in sufficient amounts for bio-
logical testing, spectral characterization, and other uses.
Also, the starting materials, especially the wide variety of
esters, are more readily available than starting materials
used with other synthetic methods [4-6]. The experimental
procedure is straightforward so that someone not necessar-
ily familiar with strong base procedures can be successful
with the reactions, and the experimental set-up does not
require an elaborate apparatus.
This initial study indicates that these polylithiated inter-
mediates and related intermediates (e.g., N-methyl or
N-carboalkoxy, etc.) have potential for condensation with
additional esters and related electrophilic compounds (e.g.,
ketones) for the preparation of new materials that may be
difficult to prepare, or even inaccessible by some of the
current synthetic methods [4-15].
atom
x
y
z
Beq
O(1)
O(2)
O(3)
N(1)
N(2)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
C(19)
C(20)
C(21)
C(22)
C(23)
C(24)
C(25)
0.3329(2)
-0.0026(2)
-0.0329(3)
0.2908(2)
0.1371(2)
0.2224(3)
0.0248(3)
-0.0229(3)
-0.0920(3)
-0.0008(4)
-0.1079(5)
-0.3097(6)
-0.3996(5)
-0.2946(4)
-0.1979(3)
-0.1816(3)
-0.3413(3)
-0.5208(3)
-0.5413(3)
-0.3812(3)
0.1635(3)
0.3414(3)
0.3673(4)
0.2199(5)
0.0443(4)
0.0160(4)
-0.0858(5)
-0.2636(7)
0.0922(8)
-0.1351(9)
-0.1560(1)
0.0412(2)
-0.1430(2)
0.0276(2)
0.0684(2)
-0.0856(2)
-0.1227(2)
-0.0212(2)
-0.2438(2)
-0.3301(3)
-0.4443(3)
-0.4740(3)
-0.3902(3)
-0.2770(3)
-0.0000(2)
0.0343(2)
0.0597(2)
0.0480(3)
0.0124(3)
-0.0107(2)
0.1890(2)
0.2545(2)
0.3708(3)
0.4246(3)
0.3595(3)
0.2424(2)
-0.2655(3)
-0.2903(5)
-0.2944(5)
-0.3230(4)
0.9569(1)
0.6627(1)
0.4893(1)
0.9424(1)
0.8921(1)
0.9214(2)
0.8589(2)
0.8410(2)
0.8212(2)
0.7942(2)
0.7575(2)
0.7470(3)
0.7749(3)
0.8124(3)
0.7731(2)
0.6859(2)
0.6249(2)
0.6489(2)
0.7333(2)
0.7954(2)
0.8980(2)
0.8896(2)
0.8980(2)
0.9136(2)
0.9208(2)
0.9148(2)
0.4876(2)
0.5278(4)
0.5509(4)
0.3794(3)
4.22(4)
4.15(4)
5.61(5)
3.37(4)
3.23(4)
3.22(5)
3.33(5)
3.08(5)
3.72(5)
4.90(7)
6.34(9)
7.27(10)
7.94(11)
5.80(8)
3.04(5)
3.11(5)
4.09(6)
4.59(6)
4.23(6)
3.78(5)
3.39(5)
4.25(6)
5.32(7)
6.05(8)
5.73(8)
4.42(6)
6.07(8)
10.4(1)
11.6(2)
11.0(2)
EXPERIMENTAL
Melting points were obtained with a Mel-Temp II melting
point apparatus in open capillary tubes and are uncorrected.
Fourier transform infrared spectra were obtained on a Nicolet
2
2
2
2
13
B
= (8/3)π [U (aa*) + U (bb*) + U (cc*) + 2U (aa*bb*)cos γ
Impact 410 FT-IR. Proton and C nuclear magnetic resonance
eq
11
22
33
12
+ 2U (aa*cc*)cos β + 2U (bb*cc*)cos α]
13
23
spectra were obtained with a Varian Associates Mercury Oxford
300 MHz nuclear magnetic resonance spectrometer, and chemi-
cal shifts were recorded in δ ppm downfield from an internal
tetramethylsilane standard. Combustion analyses were performed
by Quantitative Technologies, Inc., P.O. Box 470, Salem
Industrial Park, Whitehouse, NJ 08888. The tetrahydrofuran was
distilled from sodium (benzophenone ketyl as an indicator of dry-
ness) prior to use, and organic chemicals were obtained from
Aldrich Chemical Co.

698
Vol. 38
J. R. Downs, S. J. Pastine, J. D. Townsend, H. A. Greer, W. Kelley, Jr., D. A. Schady, T. L. McConaughy,
C. R. Metz, C. F. Beam, C. D. Almquist, W. T. Pennington and R. D. Bailey Walsch
Table 3
[48] on F was based on 2644 observed reflections (I > 3.00σ(I))
and 271 variable parameters and converged (largest parameter
Selected Bond Distances (Å) and Angles (°) for 8, C
H
N O •C H O
4 10
21 16
2
2
shift was 0.00 times its esd) with R = 0.065 and R = 0.069.
w
The standard deviation of an observation of unit weight [49]
was 1.86. The weighting scheme was based on counting statis-
O1
N1
N2
C1
C2
C4
C5
C7
C10
C11
C13
C16
C17
C19
O1
C1
N2
C3
C2
C4
C5
C6
C8
C11
C12
C14
C17
C18
C20
H1
1.352(4)
1.391(3)
1.371(4)
1.425(4)
1.476(5)
1.386(5)
1.387(6)
1.359(7)
1.390(4)
1.387(4)
1.365(4)
1.395(4)
1.362(5)
1.374(6)
0.92
O2
N1
N2
C2
C3
C4
C6
C8
C10 C15
C12 C13
C14 C15
C16 C21
C18 C19
C20 C21
C11
C1
C16
C3
C10
C9
C7
1.381(3)
1.316(4)
1.417(4)
1.382(4)
1.490(4)
1.392(5)
1.380(6)
1.375(6)
1.402(4)
1.386(4)
1.383(4)
1.387(5)
1.385(6)
1.373(5)
0.94
2
tics. Plots of Σw (|F | - |F |) versus |F |, reflection order in data
o
c
o
collection, sin θ/λ and various classes of indices showed no
unusual trends. The maximum and minimum peaks on the final
-3
difference Fourier map corresponded to 0.17 and -0.20 e Å ,
respectively. Further data are available on request from the
authors C.R.M. or W.T.P.
Neutral atom scattering factors were taken from Cromer and
C9
Waber [50]. Anomalous dispersion effects were included in F
calc
[51]; the values for ∆f' and ∆f" were those of Creagh and
McAuley [52]. The values for the mass attenuation coefficients
are those of Creagh and Hubbell [53]. All calculations were per-
formed using the teXsan [54] crystallographic software package
of Molecular Structure Corporation.
O2
H2
N2
N1
O1
N1
C1
N2
C2
C2
C4
C6
C4
C3
O2
N1
C1
C16
N1
C2
C4
C2
C10
C9
C6
C8
C8
104.7(2)
119.3(2)
121.8(3)
112.8(3)
125.9(3)
107.4(2)
131.5(3)
122.4(3)
121.4(4)
118.9(4)
120.9(4)
121.9(2)
117.6(2)
120.4(2)
120.2(3)
121.5(3)
120.4(3)
119.0(3)
119.4(4)
119.7(3)
N1
C3
O1
C1
C3
N2
C2
C5
C5
C7
C3
N2
N2
C1
C2
C2
C3
C4
C4
C6
C8
C10
C3
C16
C2
C3
C4
C10
C5
C9
C7
C9
C11
C15
C12
C13
C15
C17
C21
C19
C21
C23
111.0(2)
129.7(2)
125.4(3)
104.1(3)
130.0(3)
120.8(3)
120.4(3)
117.2(3)
120.0(4)
121.6(4)
120.3(2)
117.8(2)
122.0(2)
120.3(3)
119.6(3)
119.5(3)
120.1(3)
121.3(4)
120.5(4)
108.2(4)
General Experimental Procedure for Preparing 2'-Phenyl-
phenylacetohydrazides (1-3).
N2
C1
C1
C2
C3
C3
C4
C5
C7
C9
The entry compounds were prepared by a minor modification
of documented preparations [55] where equal amounts of the
phenylacetic acid (15 g - 0.11 mol) and phenylhydrazine (15 g
-0.14 mol) were heated under reflux for several hours using
toluene (125-150 ml) as the solvent. After reducing the volume of
the solution to 50-75 ml, crystallization usually occurred, and
after filtration, the product was recrystallized from toluene. The
work-up of a second crop for optimization of yield was not usu-
ally undertaken, and the emphasis was placed on purity and dry-
ness of phenylhydrazides.
C10 C15
C11 C10
C11 C10
O2 C11
C11 C12
C13 C14
C10 C11 C12
C12 C13 C14
C10 C15 C14
2'-Phenylphenylacetohydrazide (1).
N2
C16
N2
C16 C21
C17 C16
C17 C18
C19 C20
This compound was prepared by the general procedure from
the condensation of 15 g (0.11 mol) of phenylacetic acid and 15 g
(0.14 mol) of phenylhydrazine to yield 17.4 g (70 %); mp 173-
175° (toluene)(lit. mp 175° [56]).
C16 C17 C18
C18 C19 C20
C16 C21 C20
O3
C22
C1
O1
H1
106
C11 O2
H2
108
2'-Phenyl-(4-chlorophenyl)acetohydrazide (2).
This compound was prepared by the general procedure from
the condensation of 15 g (0.088 mol) of 4-chlorophenylacetic
acid and 15 g (0.14 mol) of phenylhydrazine to yield 13.07 g
(57%); mp 168-170° (toluene). Infrared (paraffin oil): 3313, 3238
Single crystal X-ray measurements for crystals of 8,
N O •C H O (C N O ), were collected on a
C
H
H
21 16
2
2
4
10
25 26
2
3
Mercury CCD area detector coupled with a Rigaku AFC8 diffrac-
tometer with graphite monochromated Mo-Kα radiation
(Clemson University). The data were collected at a temperature
of 20 + 1 °C to a maximum 2θ value of 52.9°. Data were col-
lected in 0.50° oscillations with 15.0 s exposures (two identical
scans were performed at each position to identify detector anom-
alies). A sweep of data was done using ω oscillations from -90.0°
to 90.0° at χ = 45.0° and φ = 0.0°. A second sweep was per-
formed using ω oscillations from -300.0° to 30.0° at χ = 45.0°
and φ = 90.0°. The crystal-to-detector distance was 26.92 mm.
The detector swing angle was 0.00°. Cell parameters and addi-
tional details of the data collection are reported in Table 1.
-1
1
(broad), 3089, 3029, 1685 (shoulder) and 1633 cm . H nmr
(DMSO-d ): δ (ppm) 3.54 (s, 2H, -CH -), 6.68-6.73, 7.10-7.42
6
2
13
(m, 9H, ArH), 7.80 (s, NH), and 9.95 (s, NH); C nmr (DMSO-
d ): δ (ppm) 39.7, 112.1, 118.6, 128.2, 128.7, 130.9, 131.3, 134.9,
6
149.3, and 169.7.
Anal. Calcd. for C
H ClN O: C, 64.40; H, 5.03; N, 10.74.
14 13 2
Found: C, 64.32; H, 5.16; N, 10.57.
2'-Phenyl-(4-methoxyphenyl)acetohydrazide (3).
This compound was prepared by the general procedure from
the condensation of 15 g (0.090 mol) of 4-methoxphenylacetic
acid and 15 g (0.14 mol) of phenylhydrazine to yield 8.53 g (37
%); mp 175-178° (toluene). Infrared (paraffin oil) 3286, 3203
Of the 10627 reflections, which were collected, 4543 were
unique (R = 0.051); equivalent reflections were merged. Data
int
-1 1
were collected and processed using CrystalClear (Rigaku) [45].
The structure was solved by direct methods [46] and expanded
using Fourier techniques [47]. The non-hydrogen atoms were
refined anisotropically. Hydrogen atoms were included but not
refined. The final cycle of full-matrix least-squares refinement
(broad), 3195, 3084, 1660 and 1635 cm . H nmr (DMSO-d ): δ
6
(ppm) 3.45 (s, 2H, -CH -), 3.73 (s, 3H, ArOCH ), 6.68-7.28 (m,
2
3
13
9H, ArH), 7.75 (s, NH), and 9.86 (s, NH); C nmr (DMSO-d ):
6
δ (ppm) 39.6, 55.1, 112.1, 118.5, 128.7, 128.8, 128.9, 132.8,
135.5, 149.3, and 170.1.

May-Jun 2001
Preparation of Substituted 1,2-Dihydro-3H-pyrazol-3-ones
699
Anal. Calcd. for C
H
N O : C, 70.29; H, 6.29; N, 10.93.
Anal. Calcd. for C H N O : C, 77.17; H, 5.30; N, 8.18.
22 18 2 2
15 16
2
2
Found: C, 70.36; H, 6.41; N, 10.94.
Found: C, 77.35; H, 5.46; N, 7.99.
General Experimental Procedure for Preparing 4,5-Disubstituted,
1,2-Dihydro-3H-pyrazol-3-ones, 4-13.
1,2-Dihydro-5-(4-chlorophenyl)-1,4-diphenyl-3H-pyrazol-3-one
(6).
This compound was prepared by the general procedure from
the condensation-cyclization of 0.015 mol of trilithiated phenyl-
hydrazide 1 and 0.016 mol of methyl 4-chlorobenzoate to yield
3.12 g (58%); mp 301° d (1-propanol-toluene). Infrared (paraffin
In a typical reaction sequence, lithium diisopropylamide
(0.063 mol for 4-7, 12 and 13 or 0.079 mol for 8 and 9) was
prepared by the addition of 39 or 49 ml of 1.6 M n-butyllithium in
hexanes (0.063 mol for 4-7, 12 and 13, or 0.079 mol for 8 and 9)
to a three-neck round-bottomed flask (e.g., 500 ml), equipped
with a nitrogen inlet tube, a side-arm addition funnel (e.g., 125
ml), and a magnetic stir bar (ratio of reagents - phenylhydrazide:
lithium diisopropylamide: ester - 1:4:1 for 4-7 and 12-13; 1:5:1
for 8 and 9: 5% molar excess of base and ester). The flask was
cooled in an ice water bath and 6.41 g or 8.02 g (0.063 mol for 4-
7, 12 and 13, or 0.079 mol for 8 and 9) of diisopropylamine, dis-
solved in 25-30 ml of dry tetrahydrofuran, was added from the
addition funnel at a fast dropwise rate during a 5 minute period
(0°, nitrogen). The solution was stirred for an additional 15-20
minutes, and then rapidly treated via a powder funnel, with a
slurry of 0.015 mol of phenylhydrazide and 50 ml of dry tetra-
hydrofuran. After 2 hours of polylithiation, 0.016 mol of ester,
dissolved in 25-35 ml of tetrahydrofuran, was added, during 5
minutes, to the polylithiated intermediate, and the solution was
stirred and condensed for 60 minutes (0°, nitrogen) for 4-7 and
10-13 and 2 hours for 8 and 9. Finally, 100 ml of 3N hydrochloric
acid was added quickly, and the two-phase mixture was well
stirred and heated under reflux for approximately 60 minutes. At
the end of this period, the mixture was poured into a large flask
containing ice (ca., 100 g), followed by the addition of 100 ml of
solvent grade ether. The mixture was then neutralized with solid
sodium bicarbonate, and the liquid layers or solid materials sepa-
rated. If a solid appeared at this point, the biphasic mixture could
be filtered using a large Buchner funnel. The aqueous layer was
extracted with ether or tetrahydrofuran (2x75 ml), and the
organic fractions were combined, dried, filtered, evaporated, and
recrystallized.
-1
1
oil) 3374 (broad), 1617 and 1598 cm . H nmr (DMSO-d ): δ
6
13
(ppm) 7.12-7.43 (m, 14H, ArH) [57]; C nmr (DMSO-d ): δ
6
(ppm) 107.3, 124.7, 125.9, 126.6, 128.1, 128.6, 128.81, 128.84,
129.3, 131.5, 132.1, 133.5, 138.6, 139.3, and 159.5.
Anal. Calcd. for C
H ClN O: C, 72.73; H, 4.36; N, 8.08.
22 15 2
Found: C, 72.85; H, 4.53; N, 8.02.
1,2-Dihydro-1,4-diphenyl-5-(4-methylphenyl)-3H-pyrazol-3-one
(7).
This compound was prepared by the general procedure from
the condensation-cyclization of 0.015 mol of trilithiated phenyl-
hydrazide 1 and 0.016 mol of methyl 4-methylbenzoate to yield
2.54 g (52%); mp 280-283° (toluene). Infrared (paraffin oil),
-1 1
3350 (broad), 1653, and 1595 cm . H nmr (DMSO-d ): δ (ppm)
6
2.27 (s, 3H, ArCH ), 7.01-7.30 (m, 14H, ArH), and 10.60 (s, NH
3
13
or OH); C nmr (DMSO-d ): δ (ppm) 20.9, 107.0, 124.4, 125.6,
126.3, 127.4, 127.9, 128.5, 128.7, 129.3, 130.0, 131.8, 138.0,
139.4, 139.9, and 159.4.
6
Anal. Calcd. for C
H N O: C, 80.96; H, 5.56; N, 8.58.
22 18 2
Found: C, 80.71; H, 5.77; N, 8.33.
1,2-Dihydro-1,4-diphenyl-5-(2-hydroxyphenyl)-3H-pyrazol-3-
one (8).
This compound was prepared by the general procedure from
the condensation-cyclization of 0.015 mol of trilithiated phenyl-
hydrazide 1 and 0.016 mol of lithiated methyl salicylate to yield
2.71 g (55%); mp 289-290° (ethanol-toluene). Infrared (paraffin
-1
1
oil) 3546, 3500, 3452, 1614 (shoulder), and 1598 cm . H nmr
(DMSO-d ): δ (ppm) 6.73-7.27 (m, 14H, ArH), 9.77 (s, 1H, OH),
6
1,2-Dihydro-1,4,5-triphenyl-3H-pyrazol-3-one (4).
13
and 10.58 (s, 1H, NH or OH); C nmr (DMSO-d ): δ (ppm)
107.3, 115.7, 118.1, 119.2, 122.9, 125.3, 125.8, 127.6, 127.8,
128.5, 130.7, 131.8, 132.4, 137.4, 140.2, 156.1, and 159.4.
6
This compound was prepared by the general procedure from the
condensation-cyclization of 0.015 mol of trilithiated phenylhy-
drazide 1 and 0.016 mol of methyl benzoate to yield 3.88 g (83%),
mp 283-285° (ethanol-toluene) (lit. mp [6] 282°). Infrared (paraffin
Anal. Calcd. for C
H N O : C, 76.81; H, 4.91; N, 8.53.
21 16 2 2
Found: C, 76.84; H, 4.88; N, 8.33.
The crystals used for X-ray analysis, mp 290-292° (tert-butyl
alcohol): Infrared 3537, 3477 (sharp), 3452 (broad), and 1593
-1
-1 1
oil) 3100-3300 cm (shoulder), 1615 and 1596 cm . H nmr
13
(DMSO-d ): δ (ppm) 7.07-7.33 (m, 15H, ArH)[57]; C nmr
6
-1
1
cm . H nmr (DMSO-d ): δ (ppm) 1.12 (s, 9H, C(CH ) ), 4.02
(DMSO-d ): δ (ppm) 107.0, 124.2, 125.5, 126.1, 127.8, 128.3,
6
3 3
6
(s, 1H, OH), 6.74-7.31 (m, 14H, ArH), 9.76 (s, 1H, OH), and
128.49 (2), 128.54, 130.0, 130.3, 131.6, 139.4, 139.7, and 159.3.
13
10.56 (s, 1H, NH or OH); C nmr (DMSO-d ): δ (ppm) 31.3,
67.0, 107.3, 115.7, 118.2, 119.2, 122.9, 125.3, 125.8, 127.6,
127.8, 128.5, 130.7, 131.8, 132.4, 137.4, 140.2, 156.1, and 159.4.
Anal. Calcd. for C
H N O: C, 80.75; H, 5.16; N, 8.97.
6
21 16 2
Found: C, 80.38; H, 5.32; N, 8.87.
1,2-Dihydro-1,4-diphenyl-5-(4-methoxyphenyl)-3H-pyrazol-3-
one (5).
Anal. Calcd. for C
H N O •C H O (C H N O ): C,
21 16 2 2 4 10 25 26 2 3
74.60: H, 6.51; N, 6.96. Found: C, 74.87; H, 6.26; N, 7.26.
This compound was prepared by the general procedure from
the condensation-cyclization of 0.015 mol of trilithiated phenyl-
hydrazide 1 and 0.016 mol of methyl 4-methoxybenzoate to yield
4.98 g (97%), mp 270-272° (ethanol-toluene). Infrared (paraffin
1,2-Dihydro-1,4-diphenyl-5-(2-hydroxy-3-methoxyphenyl)-3H-
pyrazol-3-one (9).
This compound was prepared by the general procedure from
the condensation-cyclization of 0.015 mol of trilithiated phenyl-
hydrazide 1 and 0.016 mol of lithiated methyl 3-methoxysalicy-
late to yield 4.03 g (75%); mp 272-274° (ethanol). Infrared
(paraffin oil) 3501, 3168 (broad shoulder), 1625, 1614, and 1592
-1 1
oil) 3441 (broad), 3324, 3187, 1653, 1615 and 1595 cm . H nmr
(DMSO-d ): δ (ppm) 3.73 (s, 3H, ArOCH ), 6.80-6.91, 7.06-7.30
6
3
13
(m, 14H, ArH) and 10.61 (s, NH or OH); C nmr (DMSO-d ): δ
(ppm) 55.1, 106.8, 114.1, 122.4, 124.4, 125.6, 126.2, 127.9,
128.4, 128.7, 128.8, 131.5, 131.9, 139.7, 148.3, and 159.2.
6
-1
1
cm . H nmr (DMSO-d ): δ (ppm) 3.76 (s, 3H, ArOCH ), 6.61
6
3

700
Vol. 38
J. R. Downs, S. J. Pastine, J. D. Townsend, H. A. Greer, W. Kelley, Jr., D. A. Schady, T. L. McConaughy,
C. R. Metz, C. F. Beam, C. D. Almquist, W. T. Pennington and R. D. Bailey Walsch
(t, 1H, ArH), 6.71 (d, 1H, ArH), [58] and 6.95-7.32 (m, 11H,
4.52 g (81%); mp 275-277° (xylenes-dimethylformamide).
13
-1
ArH), 8.97 (s, OH), 10.59 (s, NH or OH); C nmr (DMSO-d ): δ
Infrared (paraffin oil) 3300-3100 (shoulder), 1618, and 1593 cm .
6
-1 1
(ppm) 55.7, 107.3, 112.6, 118.3, 119.2, 122.9, 123.3, 125.4,
125.9, 127.6, 127.9, 128.6, 132.4, 137.0, 140.2, 145.4, 147.6, and
159.4.
Infrared (KBr) 1646, 1616, and 1596 cm . H nmr (trifluoroacetic
acid-d): δ (ppm) 3.79 (s, 3H, ArOCH ), 3.89 (s, 3H, ArOCH ),
3
3
13
and 6.81-7.43 (m, 13H, ArH); C nmr (DMSO-d ): δ (ppm) 54.9,
55.0, 106.5, 113.4, 114.0, 122.4, 123.9, 124.1 (2), 125.9, 128.5,
129.4, 131.3, 139.1, 139.6, 157.1, and 159.0.
6
Anal. Calcd. for C
H N O : C, 73.73; H, 5.06; N, 7.82.
22 18 2 3
Found: C, 73.62; H, 4.81; N, 7.95.
Anal. Calcd. for C
Found: C, 74.11; H, 5.29; N, 7.53.
H N O : C, 74.18; H, 5.41; N, 7.52.
23 20 2 3
1,2-Dihydro-1,4-diphenyl-5-(3,4,5-trimethoxyphenyl)-3H-pyra-
zol-3-one (10).
1,2-Dihydro-4-(4-chlorophenyl)-1,5-diphenyl-3H-pyrazol-3-one
(13).
This compound was prepared by the general procedure from
the condensation-cyclization of 0.015 mol of trilithiated phenyl-
hydrazide 1 and 0.016 mol of methyl 3,4,5-trimethoxybenzoate
to yield 5.19 g (86%); mp 270-273° (xylenes-dimethylfor-
mamide). Infrared (paraffin oil) 3374, 1660, 1602, and 1581
This compound was prepared by the general procedure from
the condensation-cyclization of 0.015 mol of trilithiated phenyl-
hydrazide 3 and 0.016 mol of methyl benzoate to yield 2.81 g
(54%); mp 302-304° (xylenes-dimethylformamide). Infrared
-1
1
cm . H nmr (DMSO-d ): δ (ppm) 3.46 (s, 6H, ArOCH ), 3.65
6
3
-1
(paraffin oil) 3300-3200 (shoulder) 1659, 1616, and 1598 cm .
(s, 3H, ArOCH ), 6.41 (s, 2H, ArH), and 7.14-7.36 (m, 10H,
3
1
1
H nmr (DMSO-d ): δ (ppm) 7.05-7.41 (m, 14H, ArH) and 10.71
ArH), and 10.59 (s, NH or OH); H nmr (trifluoroacetic acid-d):
6
13
(s, NH or OH); C nmr (DMSO-d ): δ (ppm) 105.8, 124.5,
126.5, 128.0, 128.5, 128.7, 128.8, 130.0, 130.1, 130.2, 130.3,
130.7, 139.4, 140.1, and 159.4.
δ (ppm) 3.48 (s, 6H, ArOCH ), 3.86 (s, 3H, ArOCH ), 6.42 (s,
6
3
3
2H, ArH), and 7.31-7.51 (m, 10H, ArH), and 11.50 (s, NH or
13
OH); C nmr (DMSO-d ): δ (ppm) 55.7, 60.2, 106.8, 107.8,
6
124.7, 125.3, 125.8, 126.5, 127.9, 128.68, 128.74, 131.8, 137.6,
139.7, 139.8, 152.7, and 159.4.
Anal. Calcd. for C H ClN O: C, 72.73; H, 4.36; N, 8.07.
21 15 2
Found: C, 72.83; H, 4.37; N, 8.40.
Acknowledgements.
Anal. Calcd. for C
H N O : C, 71.63; H, 5.51; N, 6.96.
24 22 2 4
Found: C, 71.91; H, 5.61; N, 6.97.
We wish to thank the following sponsors: Donors of the
Petroleum Research Fund, Administered by the American
Chemical Society, and the National Science Foundation's -
Research in Undergraduate Institutions through grant # 9708014.
The acquisition of the 300 MHz NMR spectrometer was made
possible through a National Science Foundation's Division of
Undergraduate Education grant DUE # 9750721.
3-Oxo-2-phenyl-3-(3,4,5-trimethoxyphenyl)propanoic Acid,
2-Phenylhydrazide (10a).
This compound was prepared by the general procedure exclud-
ing the cyclization step from the condensation of 0.015 mol of
trilithiated phenylhydrazide 1 and 0.016 mol of methyl 3,4,5-
trimethoxybenzoate to yield 4.80 g (76%); mp 214-218°
(xylenes). Infrared (paraffin oil) 3273 (broad), 1676 and 1668
-1
1
cm . H nmr (deuteriochloroform): δ (ppm) 3.56 (s, 1H, CH),
REFERENCES AND NOTES
3.58 (s, 6H, ArOCH ), 3.79 (s, 3H, ArOCH ), 6.66 (s, 2H, ArH),
3
3
13
7.16-7.30 (m, 10H, ArH), and 8.52 (s, NH or OH); C nmr (deu-
teriochloroform): δ (ppm) 41.5, 56.1, 61.0, 106.5, 125.8, 127.3,
127.6, 128.8, 129.0, 129.1, 129.5, 133.7, 140.1, 144.9, 152.6,
169.5 and 170.7.
[1] J. Elguero, "Pyrazoles and Their Benzo Derivatives," Section
4.04, Vol 5, Part 4A. in "Comprehensive Heterocyclic Chemistry," A. R.
Katritzky and C. W. Rees, Eds, Pergamon Press, New York, 1984. pp.
273-288, 297-301.
[2] R. H. Wiley and P. Wiley, "Pyrazolones, Pyrazolidones, and
Derivatives," Chapt. 2, Part I, Vol. 20, in "The Chemistry of Heterocyclic
Compounds," A. Weissberger, Ed, Interscience Publishers, New York,
1964, pp 46-56.
[3] A. R. Katritzky and J. M. Lagowski, Section 4.02, Vol 5, Part
4A in "Comprehensive Heterocyclic Chemistry," A. R. Katritzky and C.
W. Rees, Eds, Pergamon Press, New York, 1984. p 100.
[4] H. G. Aurich, Chem. Ber., 98, 3917 (1965).
[5] L. Capuano, W. Fisher, H. Scheidt and M. Schneider, Chem.
Ber., 111, 2497 (1978).
[6] T. Toda, M. Yoshida, T. Katayoma, and M. Minabe,
Heterocycles, 25, 79 (1987).
[7] P. T. Tomkins, K. L. Cooper, S. A. Titchmarsh, P. Appelby,
and D. G. Webber, Int. J. Immunopharmacol., 17, 357 (1995).
[8] E. A. Mohamed, M. M. Ismail, Y. Gabr, and M. Abass, Chem.
Pap., 48, 285 (1994).
[9] L. M. Liu and S. P. Xu, Yaoxue Xuebao, 30, 556 (1995).
[10] K. L. Knees, T. J. Caggiano, K. E. Steiner, J. J. Fitzgerald, Jr.,
M. J. Kates, T. E. Christos, J. M. Kulishoff, Jr., R. D. Moore, and M. L.
McCaleb, J. Med. Chem., 38, 617 (1995).
[11] V. J. Aran, M. Flores, P. Munoz, J. R. Ruiz, P. Sanchez-Verdu
and M. Stud, Ann., 817 (1995).
Anal. Calcd. for C
H N O : C, 68.55; H, 5.75; N, 6.66.
24 24 2 5
Found: C, 68.41; H, 5.78; N, 6.60.
1,2-Dihydro-1,4-diphenyl-5-(4-(1,1-dimethylethylphenyl)-3H-
pyrazol-3-one (11).
This compound was prepared by the general procedure from
the condensation-cyclization of 0.015 mol of trilithiated phenyl-
hydrazide 1 and 0.016 mol of ethyl 4-t-butylbenzoate to yield
3.42 g (62%); mp 310-312° (xylenes-dimethylformamide).
-1 1
Infrared (paraffin oil) 3400 (broad), 1620 and 1596 cm . H nmr
(DMSO-d ): δ 1.24 (s, 9H, ArC(CH ) ), 7.07-7.37 (m, 14H,
6
3 3
13
ArH,), and 10.58 (s, NH or OH); C nmr (DMSO-d ): δ 30.9,
34.3, 106.9, 124.1, 125.0, 125.4, 126.0, 127.2, 127.6, 128.26,
128.32, 129.6, 131.6, 139.5, 139.7, 150.9, and 159.1.
6
Anal. Calcd. for C
H N O: C, 81.49; H, 6.56; N, 7.60.
25 24 2
Found: C, 81.53; H, 6.48; N, 7.43.
1,2-Dihydro-4,5-di-(4-methoxyphenyl)-1-phenyl-3H-pyrazol-3-
one (12).
This compound was prepared by the general procedure from
the condensation-cyclization of 0.015 mol of trilithiated phenyl-
hydrazide 2 and 0.016 mol of methyl 4-methoxybenzoate to yield
[12] J. A. G. Agundez, C. Martinez, and J. Bemitez, Xenobiotica,
25, 417 (1995).

May-Jun 2001
Preparation of Substituted 1,2-Dihydro-3H-pyrazol-3-ones
701
[13] O. M. Habib, M. M. Girges, E. B. Moawad, and A. M. El-
Shafei, Boll. Chim. Farm., 134, 209 (1995).
[14] M. M. Girges, M. A. Hanna, and S. N. Ayyad, Boll. Chim.
Farm., 134, 204 (1995).
[15] M. M. Girges, M. A. Hanna, and S. N. Ayyad, Phosphorus,
Sulfur, Silicon Relat. Elem., 104, 5 (1995).
[16] J. Elguero, C. Mazin, A. R. Katritzky, and P. Linda, "The
Tautomerism of Heterocycles", Advances in Heterocyclic Chemistry,
Supplement 1, pp. 339-346 (1976).
[17] F. Bechtel, J. Gaultier, and C. Hauw, Cryst. Struct. Commun.,
2, 473 (1973).
[18] V. H. Dom, J. Prakt. Chem., 315, 382 (1973).
[19] J. Feeney, G. A. Newman, P. J. S. Pauwels, J. Chem. Soc., C,
1842 (1970).
[20] J. Wolff and M. Taddei, Tetrahedron, 42, 4267 (1986).
[21] I. V. Magedov and Y. I. Smushkevich, Khim. Geterotsikl.
Soedin., 933 (1991).
[41] A. J. Angel, A. E. Finefrock, J. D. Townsend, T.-Ha V.
Nguyen, D. R. Hurst, F. J. Heldrich, C. F. Beam, and I. T. Badejo, J.
Heterocyclic Chem., 36, 1231 (1999).
[42] The lithiation time and the ratio of the reagents is what has been
noted for presumed trilithiation. See: [a] C. F. Beam, R. S. Foote, and C. R.
Hauser, J. Chem. Soc., C, 1658 (1971); [b] C. F. Beam, R. S. Foote, and C. R.
Hauser, J Heterocyclic Chem., 9, 183 (1972); [c] See ref. [35]; [d] C. F.
Beam, M. A. Hines, C. L. Mazat, D. C. Duncan, D. Beckman, R. J.
Lachicotte, R. C. Tummons, and N. D. Heindel, Chem. and Indust. (London),
1989, 727; [e] D. R. Hurst, K. L. French, A. J. Angel, A. R. Williams, M. E.
Rampey, T. S. Guion, K. W. Chan, C. M. Kassis,, S. L Studer-Martinez, and
C. F. Beam, J. Heterocyclic. Chem., 35, 1357 (1998); [f] See ref. [39]; [g] A.
J. Angel, A. E. Finefrock, K. L. French, D. R. Hurst, A. R. Williams, M. E.
Rampey, S. L. Studer-Martinez and C. F. Beam, Can. J. Chem. 77, 94 (1999).
[43] Most of the products did not display a clearly assignable car-
-1
bonyl absorption between 1620-1680 cm , or a convincing or definitive
-1
OH absorption in the region 3100-3500 cm .
[22] I. V. Magedov and Y. I. Smushkevich, Synthesis, 845 (1991).
[23] M. J. Kornet, T. H. Ong, and P. A. Thio, J. Heterocyclic
Chem., 8, 999 (1971).
[24] K. N. Zelenin, A. V. Dovgilevich, I. P. Bezhan, G. A.
Golubeva, L. A. Sviridova, L. V. Pastushenkov, E. G. Gromova, T. A.
Gatchina, and S. V. Pomogaibo, Khim. Geterotsikl. Soedin., 659 (1984).
[25] F. Boberg and R. Schardt, Justus Liebigs Ann. Chem., 734,
173 (1970).
[26] M. U. Koller, A. C. Church, C. L. (Mazat) Griffith, M. A.
Hines, R. J. Lachicotte, R. A. Taylor, and C. F. Beam, Synth. Commun.,
26, 1763 (1996).
[27] D. C. Reames, C. E. Harris, L. W. Dasher, R. M. Sandifer, W.
M. Hollinger, and C. F. Beam, J. Heterocyclic Chem., 12, 779 (1975).
[28] T. D. Fulmer, L. P. Dasher, B. L. Bobb, J. D. Wilson, K. L.
Sides, and C. F. Beam, J. Heterocyclic Chem., 17, 799 (1980).
[29] J. D. Wilson, T. D. Fulmer, L. P. Dasher, and C. F. Beam, J.
Heterocyclic Chem., 17, 389 (1980).
[44] This example was chosen because the condensation-cycliza-
tion of trilithiated 1 with lithiated methyl thiosalicylate did not give the
analogous dihydropyrazolone with a pendent phenyl mercaptan pendant
group in position 5. An isothioflavone was obtained instead, which will
be reported on completion with other results separately.
[45] Computer program, CrystalClear: Rigaku Corporation,
Danvers, MA 01923, (1999).
[46] G. M. Sheldrick, Computer program, SHELXS86 in
"Crystallographic Computing 3," G.M. Sheldrick, C. Kruger and R.
Goddard, Ed., Oxford University Press, London, (1985), pp. 175-189.
[47] P. T. Beurskens, G. Admiraal, G. Beurskens, W. P. Bosman, R.
de Gelder, R. Israel, and J. M. M. Smits, in "The DIRDIF-94 Program
System," Technical Report of the Crystallography Laboratory, University
of Nijmegen, The Netherlands, (1994).
2
[48] Least Squares function minimized: Σw(|F |-|F |)
o
c
[49] Standard deviation of an observation of unit weight: [Σw(|F |-
|F |)2/(N -N )] where: N = number of observations and N = number
o
1/2
c
o
v
o
v
[30] M. J. Livingston, M. F. Chick, E. O. Shealy, D. J. Park, T. D.
Fulmer, and C. F. Beam, J. Heterocyclic Chem., 19, 215 (1982).
[31] A. M. Huff, H. L. Hall, M. J. Smith, S. A. O'Grady, F. C.
Waters, R. W. Fengl, J. A. Welch, and C. F. Beam, J. Heterocyclic Chem.,
22, 501 (1985).
[32] C. F. Beam, H. L. Hall, A. M. Huff, R. C. Tummons, S. A.
O'Grady, J. Heterocyclic Chem., 21, 1897 (1984).
[33] A. M. Huff and C. F. Beam, J. Heterocyclic Chem., 23, 1343
(1986).
[34] D. C. Duncan, T. A. Trumbo, C. D. Almquist, T. A. Lentz, and
C. F. Beam, J. Heterocyclic Chem., 24, 555 (1987).
[35] C. L. Mazat, C. F. Beam, and M. A. Hines, Synth. Commun.,
20, 253 (1990).
[36] A. C. Church, M. U. Koller, M. A. Hines, and C. F. Beam,
Synth. Commun., 26, 3659 (1996).
of variables.
[50] D. T. Cromer and J. T. Waber, in "International Tables for
X-ray Crystallography," Vol. IV, The Kynoch Press, Birmingham,
England, Table 2.2 A, (1974).
[51] J. A. Ibers and W. C. Hamilton, Acta Crystallogr., 17, 781
(1964).
[52] D. C. Creagh and W. J. McAuley, in "International Tables for
Crystallography," Vol C, A. J. C. Wilson, ed., Kluwer Academic
Publishers, Boston, Table 4.2.6.8, (1992), pp. 219-222 .
[53] D. C. Creagh and J. H. Hubbell, in "International Tables for
Crystallography," Vol C, A. J. C. Wilson, Ed., Kluwer Academic
Publishers, Boston, Table 4.2.4.3, (1992), pp. 200-206.
[54] Computer program, teXsan for Windows version 1.06: Crystal
Structure Analysis Package, Molecular Structure Corporation, The
Woodlands, TX 77381-5209 (1997-9).
[37] A. C. Church, M. U. Koller, S. A. O'Grady, and C. F. Beam,
Synth. Commun., 26, 2603 (1996).
[38] C. F. Beam, S. E. Davis, T. L. Cordray, K W. Chan, C. M.
Kassis, J. G. Freeman, G. M. Latham, T. S. Guion and, K. C. Hildebran,
A. C. Church, M. U. Koller, C. R. Metz, W. T. Pennington, and K. L.
Schey, J. Heterocyclic Chem., 34, 1549 (1997).
[55] R. L. Shriner, C. K. F. Hermann, T. C. Morrill, D. Y. Curtin,
and R. C. Fuson in "The Systematic Identification of Organic
Compounds," Seventh Edition, John Wiley and Sons, Inc. New York,
New York, (1998), pp. 313-314.
[56] See ref. [55], p. 568.
1
[57] The H nmr spectrum of 4 and 6 did not display NH/OH
[39] M. E. Rampey, D. R. Hurst, A. Sood, S. L. Studer-Martinez,
and C. F. Beam, Synth. Commun., 29, 495 (1999).
absorptions.
1
[58] A comparative H nmr spectrum was obtained from methyl 3-
[40] M. E. Rampey, C. E. Halkyard, A. R. Williams, A. J. Angel,
D. R. Hurst, J. D. Townsend, A. E. Finefrock, C. F. Beam, and S. L.
Studer-Martinez, Photochem. and Photobiol., 70, 176 (1999).
methoxysalicylate, and it displayed apparent (δ) t, 6.78, d, 7.00 and d,
7.39 ppm. A similar spectral splitting as observed with this product 9 for
the two upfield proton absorptions.