Hydrogen-bonded double strands: Crystal structure and spectroscopic properties of a 2,2′-dipyrryl ketone

Article abstract of DOI:10.1007/s007060070060

The synthesis, crystal structure determination, conformational analysis, and spectroscopic properties of 3,3′-diethyl-4,4′-dimethyl-2,2′-dipyrryl ketone (1) are reported. The dipyrryl ketone is a model for the dipyrrole core of 10-oxobilirubin, a presumed metabolite in alternate pathways of excretion of the yellow pigment of jaundice, bilirubin. In the crystal, 1 adopts a helical conformation, with a molecule of one helicity being hydrogen-bonded to two molecules of the opposite helicity. Thus, 1 self-assembles via hydrogen bonding into supramolecular double-stranded arrays, where molecules of the same helicity comprise one strand and are paired through hydrogen bonding to molecules of opposite helicity in the second strand. In the observed molecular conformation each pyrrole ring and adjacent carbonyl group are rotated into an sc conformation (torsion angle ～ 29°), with each N-H pointing in the same direction as the C=O. Molecular mechanics/dynamics calculations predict the sc,sc conformation, absent hydrogen bonding, to be the most stable, but only by a few tenths of a kj/mol. In CHCl₃, 1 is monomeric according to vapor pressure osmometry studies (MW_obs = 251 ± 10 vs. MW_calc = 244). ¹H NMR NH chemical shifts in CDCl₃ suggest a predominantly anti orientation of the C = O and pyrrole NHs, which is opposite to the orientation observed in the crystal.

Full text of DOI:10.1007/s007060070060

Monatshefte fuÈr Chemie 131, 825±838 (2000)
Hydrogen-Bonded Double Strands: Crystal
Structure and Spectroscopic Properties
of a 2,20-Dipyrryl Ketone
Michael T. Huggins, Adrianne K. Tipton, Qingqi Chen,
Ã
and David A. Lightner
Department of Chemistry, University of Nevada, Reno, NV 89557-0020, USA
Summary. The synthesis, crystal structure determination, conformational analysis, and spectro-
scopic properties of 3,30-diethyl-4,40-dimethyl-2,20-dipyrryl ketone (1) are reported. The dipyrryl
ketone is a model for the dipyrrole core of 10-oxobilirubin, a presumed metabolite in alternate
pathways of excretion of the yellow pigment of jaundice, bilirubin. In the crystal, 1 adopts a helical
conformation, with a molecule of one helicity being hydrogen-bonded to two molecules of the
opposite helicity. Thus, 1 self-assembles via hydrogen bonding into supramolecular double-stranded
arrays, where molecules of the same helicity comprise one strand and are paired through hydrogen
bonding to molecules of opposite helicity in the second strand. In the observed molecular
conformation each pyrrole ring and adjacent carbonyl group are rotated into an sc conformation
(torsion angle ꢀ 29ꢁ), with each N-H pointing in the same direction as the C=O. Molecular
mechanics/dynamics calculations predict the sc,sc conformation, absent hydrogen bonding, to be
the most stable, but only by a few tenths of a kj/mol. In CHCl3, 1 is monomeric according to vapor
pressure osmometry studies (MWobs ˆ 251 Æ 10 vs: MWcalc ˆ 244). 1H NMR NH chemical shifts in
CDCl3 suggest a predominantly anti orientation of the C ˆ O and pyrrole NHs, which is opposite to
the orientation observed in the crystal.
Keywords. Pyrrole; Conformation; Hydrogen bonding.
Introduction
Bilirubin (Fig. 1) is the yellow pigment of jaundice [1, 2]. In healthy adults some
300 mg of bilirubin are produced each day and secreted by the liver into bile as
glucuronide conjugates [1]. 10-Oxo-bilirubin (Fig. 1) has been suggested as a
metabolite formed in alternative (oxidative) pathways for elimination of bilirubin
[3]. Whereas the structure, metabolism, and photochemistry of bilirubin have received
much attention in recent years, far less is known of 10-oxobilirubin. Much of what
we know of the properties of bilirubin was anticipated through stereochemical and
photochemical studies of its dipyrrole analogs, dipyrrinones and dipyrrylmethanes
(Fig. 1), and most of the stereochemical studies of these dipyrrolic analogs come
from X-ray crystallography and molecular mechanics calculations [4]. The ®rst and
Ã
Corresponding author

826
M. T. Huggins et al.
Fig. 1. Constitutional structures of dipyrrylketone analogs (1 and 2) of 10-oxobilirubin and a
dipyrrylmethane (3) analog of bilirubin
only crystal structure of a dipyrrylmethane (3) was presented by Bonnett et al. [5].
This was followed by crystal structures of bilirubin [6] and several dipyrrinones
[7]. Conformational analysis of dipyrrylmethanes and dipyrrinones was provided
by CNDO/2 molecular orbital calculations and by molecular mechanics methods
[4, 8]. Until very recently, however, there was little information available on the
stereochemistry of dipyrryl ketone analogs of 10-oxobilirubin. A crystallographic
structure of the parent compound, 2,20-dipyrryl ketone (2), indicated a preference
for the sp,sp conformation, with one pyrrole NH and the carbonyl participating in
intermolecular hydrogen bonding [9]. Interestingly, molecules of 2 in the crystal
are arranged in supramolecular helicies, and, like benzil [10], all molecules have
the same helicity in a given crystal. However, the relevance of this information to
the stereochemistry of 10-oxobilirubin is unclear, given that the latter has pyrrole
ꢀ-substituents that might tend to sterically disfavour the sp,sp conformation
observed for 2. In the following we report on the synthesis, crystal structure, and
conformational analysis of the ꢀ-substituted dipyrryl ketone 1.
Results and Discussion
Synthetic aspects
Our approach to the preparation of 1, as outlined in Scheme 1, involved conversion
of a suitable monopyrrole (7) to a dipyrrylmethane (6) [11], followed by oxidation
to an oxo-dipyrrylmethane (5) and then removal of the carboethoxy groups. Thus,
the target dipyrryl ketone 1 was synthesized in six steps from the readily available
monopyrrole 8 [12], which was conveniently reduced to 7 under Clemmensen
conditions [13]. Monobromination of the C(5) methyl group of 7 was accom-
plished using bromine in ethyl acetate, and the resulting bromomethyl derivative
was solvolyzed in methanolic hydrochloric acid to afford 6 [11, 14] in high yield.
Oxidation of the central methylene group of 6 could be achieved in comparable
yield either by treatment with ceric ammonium nitrate [15] or by reaction with

Structure and Properties of a 2,20-Dipyrryl Ketone
827
Scheme 1
sulfuryl chloride followed by hydrolysis [16]. Although 5 could be saponi®ed
easily and in high yield to 4, the dicarboxylic acid resisted decarboxylation by
conventional methods. However, we found that 4 underwent smooth loss of CO2 in
molten sodium acetate trihydrate to give 1.
Molecular geometry from X-ray crystallography and molecular dynamics
calculations
Previously, only two related dipyrrole structures had been established by X-ray
analysis: dipyrrylmethane 3 [5] of Fig. 1 and the simplest 2,20-dipyrryl ketone (2)
[9]. Both exhibit intermolecular hydrogen bonding in the crystal: monoclinic 3 as
hydrogen-bonded dimers, orthorhombic 2 as a hydrogen-bonded oligomer. The
latter is particularly interesting, as individual crystals are homochiral, with
molecules of 2 all having the same helicity (torsion angles ꢁ1 ꢀ 13ꢁ; ꢁ2 ꢀ 10ꢁ) and
being arrayed along a helical chain (Fig. 2A) with intermolecular hydrogen
bonding linking one molecule to the next.
The crystal structure of 1 is rather different from that of 2. Two crystal-
lographically unique molecules (A and B, Fig. 2B) of 1 are found in the unit cell
Fig. 3A). A and B have nearly mirror image shapes but are not true enantiomers;
and they are organized very differently in the crystal, as compared with 2.
Molecules of 1 do not fall into helical arrays with each molecule hydrogen bonded
to the next but are arranged in strands consisting of only A or only B conformers.
Side-by-side A molecules in one strand are tethered by a network of hydrogen
bonds to side-by-side B molecules in a second strand (Fig. 2B), and these double
strands extend inde®nitely through the crystal lattice. Although the A molecules
are not hydrogen bonded to other A molecules, nor are B hydrogen bonded to B,
each molecule of one strand is hydrogen bonded to two molecules of the second
strand of the duplex using both NHs and the carbonyl of each molecule. Thus, in
the crystal structure of 1 there are four hydrogen bonds to each molecule, whereas
in 2 there are only two, as only one NH is used in hydrogen bonding. As with 2, the

828
M. T. Huggins et al.
Fig. 2. (A) Ball and stick (Ref. 4) representation of 2,20-dipyrryl ketone (2) in an intermolecularly
hydrogen-bonded helical array in its crystal [9]. All molecules of 1 adopt the sp,sp conformation and
all have the same helicity. (B) Crystal structure drawing of 1 showing strands of A and B molecules,
with each A molecule hydrogen-bonded to two B molecules, and each B molecule hydrogen-bonded
to two A molecules. A and B have opposite helicity and similar sc,sc conformations but are not
enantiomers
Ê
N to O nonbonded distances of the N±HÁ Á ÁO=C hydrogen bond are 2.89 to 2.92 A,
Ê
which equals approximately the sum (2.90 A) of the van der Waals radii of O
and N. Molecules A and B are more twisted (helical) than those of 2, with
torsion angles {ꢁ1 ꢀ ꢁ2 ꢀ 29ꢁ in A and ꢁ1 ꢀ 25ꢁ; ꢁ2 ꢀ 32ꢁ in B (vs. ꢁ1 ꢀ 13ꢁ;
ꢁ2 ꢀ 10ꢁ in 2). Thus, crystals of 1 are not homochiral as in 2, and intramolecular
steric repulsion between pyrrole ꢀ-alkyl groups of adjacent rings (3,30 of Fig. 1)
apparently increases the torsion angles and hence the interplanar angle of 1 (A:
59ꢁ, B: 62ꢁ), which is about twice as large as that of 2 (25ꢁ).
Molecular dynamics calculations indicate a slight preference for the ac,sc
conformation of 1 (Table 1) over the sc,sc and ac,ac conformers. The computed
differences are too small to be meaningful. The sc,sc conformation with ꢁ1 ꢀ 37ꢁ;
ꢁ2 ꢀ 36ꢁ is only 0.8 kj/mol higher in energy than the ac,-sc, and this sc,sc

Structure and Properties of a 2,20-Dipyrryl Ketone
829
Fig. 3. (A) Molecular packing and unit cell of 1 in the projection (010), viewed down the b axis. (B)
The numbering system used in the crystal structure of 1 shown for carbon, nitrogen, and oxygen (O)
atoms of A and B

830
M. T. Huggins et al.

Structure and Properties of a 2,20-Dipyrryl Ketone
831
conformation is very close to that seen in the crystal. There is no strong energy bias
against the ac,ac conformer, which is the conformation adopted by the central
dipyrrole core of bilirubin, and probably by its 10-oxo analog (Fig. 1). In contrast,
molecular dynamics calculations of 2 indicate a strong bias for the sp,sp conformer,
nearly the same as that found in the crystal, over the ac,-sp and the ac,ac
conformers. Although only one of the two pyrroles of 2 is involved in hydrogen
bonding in the crystal, the computations provide a rationale for ®nding only the
sp,sp conformer in the crystal lattice.
Substituents at the pyrrole ꢀ-positions, especially at 3 and 30, might be expected
to destablize the sp,sp conformation by steric repulsions between the R0 groups
(Table 1). Molecular dynamics calculations on 1 support an sc,sc conformation over
sp,sp, but the sc,sc conformation is destabilized by steric repulsions and thus closer
in energy to the ac,-sc and ac,ac conformations that are disfavoured in 2.
State of aggregation in solution
Vapor pressure osmometry (VPO) measurements have proven useful in detecting
aggregation of pyrrolic compounds in solution, especially linear di- and tetrapyrroles
[4, 17]. In dimerization-promoting non-polar solvents such as chloroform,
dipyrrinones form tight dimers, and bilirubin diesters are mainly dimeric, probably
through the action of intermolecular hydrogen bonding. In our studies, in which we
used benzil as a calibration standard, we found that 1 is monomeric in chloroform
solution in the range of 2:8 8:2 Â 10 3 mol/kg (Table 2). VPO measurements also
indicate that 2 and its monopyrrole analog, pyrrole ꢂ-aldehyde, are monomeric in
chloroform.
Table 2. Molecular weightsa of related pyrroles (1, 2, and pyrrole ꢂ-aldehyde in CHCl3 at 45ꢁC)
Actual
MW
Observed
MW
Conc. Range
(mol/kg)
3
244
160
251Æ10
164Æ10
2.8 8.2Â10
4.1 13.2Â10
3
2
95
89Æ10
1.1 3.2Â10
a
Benzil (MW 210) served as the calibration standard, giving an observed molecular weight of
220Æ15 for a concentration range of 3.9 17.7Â10 3 mol/kg

832
M. T. Huggins et al.
Hydrogen bonding in solution
1
From H NMR spectroscopy, pyrrole NH signals can often reveal information on
hydrogen bonding, both intramolecular and intermolecular [4, 17, 18]. Since VPO
studies of 1 and 2 indicate monomeric solutions, it remained to be seen whether
intramolecular hydrogen bonding could be detected. Consistent with monomeric
solutions, the N±H chemical shifts (Table 3) of 1, 2, and pyrrole ꢂ-aldehyde show
little variation over a 100-fold difference in concentration, and the chemical shifts
are nearly the same for each of these compounds at the same concentration. Since
we have no model compounds similar to those of Table 3 that are (or are not)
conclusively intramolecularly hydrogen-bonded, we turned to an examination of the
N±H stretch in their infrared spectra. Kuhn and Kleinspehn [19] have observed that
for a series of dipyrrylmethane diesters, 9 exhibited N±H stretching in carbon
1
1
tetrachloride near 3450 cm , whereas 10 exhibited two bands, one near 3450 cm
1
1
and the other near 3350 cm , and 11 exhibit only one band near 3400 cm
(Table 4). Compound 9 is incapable of intramolecular hydrogen bonding, and its
vN is at 3458 cm , but 10 can adopt a conformation where the N±H (vN
H
1
ˆ
H
1
3361 cm ) of one pyrrole ring hydrogen bonds to the ꢂ-carboethoxy carbonyl on
1
the other pyrrole ring, leaving one N±H (vN ˆ 3466 cm ) free of hydrogen
H
bonding. The hydrogen-bonded N±H appears at lower wavenumber as expected. In
11, both pyrrole N±Hs can engage in hydrogen bonding, each to a carboethoxy
1
group of the opposing ring, hence vN ˆ 3397 cm . The N±H stretching data for
H
1
1, 2, and pyrrole ꢂ-aldehyde all show the higher wavenumber band near 3450 cm ,
and none of them shows a band corresponding to hydrogen-bonded N±H.
Consequently, we believe that both 1 and 2 are monomeric in solution and neither
engages in intramolecular hydrogen bonding.
Conformation in solution
It is dif®cult to assess the conformation of dipyrryl ketones in solution. So far as we
are aware, there is relatively little information as to whether the ketone carbonyl
prefers to be anti to the pyrrole NHs, or syn as required for intermolecular
hydrogen bonding and observed in crystals of 1 and 2. A study of NH chemical
1
shifts in the H NMR spectra of 2-pyrryl ketones and esters (Table 5) suggests a
way to distinguish syn and anti conformations. In the syn orientation, the N±H lies
in a carbonyl deshielding cone [20] and is thus expected to appear ꢀ 1 ppm
1
Table 3. Concentration dependence of the NH H NMR chemical shifts (ppm) of 1, 2, and pyrrole
ꢂ-aldehyde in CDCl3 at 25ꢁC
Concentration
Pyrrole NH Chemical Shift (ꢃ; ppm)a
(M)
Dipyrryl Ketone
Dipyrryl Ketone
Pyrrole
1
2
ꢂ-Aldehyde
0.01
8.51
8.49
8.49
9.50
9.43
9.40
9.64
9.58
9.55
0.001
0.0001
a
Down®eld from TMS at 500 MHz

Structure and Properties of a 2,20-Dipyrryl Ketone
833
Table 4. Comparison of infrared N-H stretching vibrations (cm 1) in selected dipyrrylmethanes and
dipyrryl ketonesa
2
b
aIn CCl4 at ꢀ10 M; data from Ref. 19
a
Table 5. Observed NH chemical shifts ꢂꢃNH; ppm† for pyrrole ꢂ-aldehydes, ketones, and esters in CDCl3 vs. heats of
formation for syn and anti conformers
syn
anti
ÁÁHfb (kj/mol) ꢁscynꢂꢁ†
syn
anti
ÁÁHfb (kj/mol) ꢁscynꢂꢁ†
R
ꢃN
ꢁcantiꢂꢁ†
ꢃN
ꢁanticꢂꢁ†
149
137
156
115
H
H
Hd
9.6
9.4
9.2
9.6
11.3
7.9
1.5
3.6
0
0
0
0
180
180
180
125
9.4f
8.9f
8.8g
8.6h
11.7
0
39
26
±
Med
OMed
tBue
0.8
4.2
±
a Down®eld from TMS; b difference in heat of formation (ÁHfꢂsyn† ÁHfꢂanti†) as determined by PCModel molecular
mechanics calculations using the MMX force®eld (Serena Software, Bloomington, Indiana, USA); c Torsion angles N±C±
C=O for syn or anti isomers in their minimum energy conformations determined from PCModel molecular mechanics
calculations; d Fischer H, Orth H (1934) Die Chemie des Pyrrols, Akademische Verlagsgesellschaft mbH, Leipzig, vol I,
pages 152 (R=H), 183 (R ˆ CH3), and 237 (R ˆOCH3); e Mirachi D, Ritchie GLD (1984) J Mol Struct 116: 337; f Fischer
H, Hofelmann H (1938) Liebigs Ann Chem 533: 216; g Manitto P, Monti P (1980) J Chem Soc Chem Commun 178 (for
the ethyl ester); h New compound, prepared by reaction of 3,4-dimethylpyrrole Grignard with pivaloyl chloride to give the
pyrryl ketone of the correct molecular weight and spectroscopic data

834
M. T. Huggins et al.
down®eld of the N±H when the orientation is anti. An especially nice example may
be found in the cisoid ꢂ; ꢀ-unsaturated (H2C=C±C=O) ketone of the natural
product lemnalol, where the ole®nic syn hydrogen, which lies in the same position
relative to the carbonyl group as in sp- or sc-1, resonates at 6.01 ppm, whereas the
anti proton appears at 5.04 ppm [21].
Experimental
All UV/Vis spectra were recorded on a Perkin-Elmer ꢄ-12 spectrophotometer, infrared spectra were
measured on a Perkin-Elmer Spectrum BX FT-IR system, and all nuclear magnetic resonance
(NMR) spectra were obtained on a GE QE-300 300-MHz spectrometer. Chemical shifts are reported
in ꢃ (ppm) referenced to the residual CHCl3 1H signal at 7.26 ppm and the 13C signal at 77.0 ppm.
Melting points were taken on a Mel-temp capillary apparatus and are uncorrected. Vapor pressure
osmometry measurements were performed on a Gonotec Osmomat 070 osmometer calibrated with
benzil at 45ꢁC in CHCl3. Combustion analysis of 1 was performed by Desert Analytics, Tucson,
AZ, giving data in satisfactory agreement with the calculated values. Analytical thin layer
chromatography was carried out on J. T. Baker silica gel IB-F plates (125 m layers). Spectroscopic
data were obtained in spectral grade solvents (Aldrich or Fisher). Bromine and ceric ammonium
nitrate (CAN) were purchased from J. T. Baker Co., tri¯uoroacetic acid, ethyl acetate, and sulfuryl
chloride from Acros Organics, dichloromethane, methanol, and acetic acid from Fisher. The
crystalline starting material, ethyl 4-acetyl-3,5-dimethylpyrrole 2-carboxylate (8), is readily
available (74% yield) by a Fischer-Knorr type reaction of the oxime of ethyl acetoacetate with
pentan-2,4-dione in the presence of zinc powder [12]. The acetyl group of 8 can be smoothly reduced
using zinc in methanolic hydrochloric acid to afford 60% or higher [13] yields of ethyl 3,5-dimethyl-
4-ethylpyrrole 2-carboxylate (7). The latter served as the immediate precursor to dipyrrylmethane 6,
whose improved synthesis in 80% yield is reported below. Previously [15a], we had reported on the
conversion of 6 to dipyrryl ketone 5 in ꢀ60% yield using ceric ammonium nitrate (CAN) as
oxidizing agent [15b]. In the current study, 5 was saponi®ed in 99% yield and decarboxylated in 70%
yield to afford the target dipyrryl ketone 1 [16]. In the following, we report improved methods or
yields for 6 and 1 from their immediate precursors.
3,30-Diethyl-4,40-dimethyl-5,50-bis-(ethoxycarbonyl)-2,20-dipyrrylmethane (6; C21H30N2O)
Ethyl 3,5-dimethyl-4-ethylpyrrole 2-carboxylate (7, 14.4 g, 73.8 mmol), prepared from 8 as
described previously [13], was dissolved in 100 cm3 ethyl acetate; then 11.8 g Br2 (73.8 mmol, 1.0
equiv.) were added dropwise over 15 min. After all the Br2 had been added, a considerable amount of
a yellow solid had precipitated from the solution. The mixture was allowed to stir for another hour at
room temperature before removing the solvent to dryness using a rotary evaporator. The yellow solid
residue was dissolved directly in 100 cm3 methanol containing 2 cm3 of conc. hydrochloric acid. The
amount of solvent used is a key factor in leading to a good yield. Too much solvent leads to low
yields of product; the less solvent, the better the result. The mixture was heated to re¯ux for 1 h
before cooling to 0ꢁC and adjusting the pH to 7 using 10% aqueous ammonia. The resulting white
precipitate was collected by suction ®ltration and recrystallized from 70% aqueous methanol to yield
the desired compound.
Yield: 11 g (80%); m.p.: 125±126ꢁC (Lit.: m.p.: 122±123ꢁ[14], 124±125ꢁC [22], 126±127ꢁC [23],
126ꢁC [24]; IR (®lm): ꢅ ˆ 3313, 2963, 2928, 2869, 1652, 1444, 1278, 1252 cm 1; 1H NMR (CDCl3,
ꢃ, 300 MHz): 1.04 (t, J ˆ 6.0 Hz, 6H), 1.29 (t, J ˆ 7.3 Hz, 6H), 2.27 (s, 6H), 2.41 (q, J ˆ 6.0 Hz, 4H),
3.88 (s, 2H), 4.23 (q, J ˆ 7.3 Hz, 4H), 9.31 (brs, 2H) ppm; 13C NMR (CDCl3, ꢃ, 75 MHz): 10.24 (q),
14.25 (q), 15.14 (q), 17.03 (t), 22.77 (t), 59.67 (t), 117.77 (s), 123.95 (s), 126.72 (s), 128.72 (s),
161.69 (s) ppm.

Structure and Properties of a 2,20-Dipyrryl Ketone
835
3,30-Diethyl-4,40-dimethyl-2,20-dipyrryl ketone (1; C15H20N2O)
Keto diester 5 [15b] (4.8 g, 0.124 mol) and 2 g, NaOH (0.05 mol, 4.1 equivs.) were dissolved in
80 cm3 of 95% ethanol and 20 cm3 H2O. The mixture was heated at re¯ux for 3 h, and the solvent
was evaporated (rotovap). The residue was taken up in 80 cm3 sat. aqueous NaNO3 solution, cooled
to 20ꢁC, and acidi®ed to pH ꢀ 6 by adding a solution of 10% HCl (made up from conc. HCl and
sat. aqueous NaNO3 solution). The white diacid precipitate was collected by ®ltration and air dried to
give a crude yield of 99%. The dried diacid (4, 100 mg, 0.3 mmol) was mixed with 3 g sodium
acetate trihydrate and heated at 260ꢁC for 1 h under vacuum (1 torr). After cooling to room
temperature, the residue was washed with dichloromethane (2Â50 cm3), the combined organic
phases were washed with 2Â50 cm3 sat. NaHCO3 solution, and dried over anhydrous Na2SO4. After
removing the CH2Cl2 (rotovap) the residue was recrystallized from CH2Cl2-hexane.
Yield: 51 mg (70%); m.p.: 180±182ꢁC (Ref. [16]: m.p.: 180±180.5ꢁC; IR (®lm): ꢅ ˆ 3254, 2967,
max
343
max
295
1
2934, 2853, 1576, 1560 cm 1; UV/Vis (ethanol): ꢆ ˆ 18000; ꢆ ˆ 9900; H NMR (CDCl3, ꢃ,
Table 6. Crystallographic data for 2,20-dipyrryl ketone 1
Formula weight
Crystallized from
Temperature (K)
Crystal size (mm)
Formula
488.7
methanol-dichloromethane
298(2)
0.26Â0.52Â0.44
C30H40N4O2
Space group
Z
P-1
2
Ê
Cell dimensions
a ˆ7.7330(8) A
Ê
b ˆ12.1415(7) A
Ê
c ˆ16.1395(17) A
ꢂ ˆ104.957(6)
ꢀ ˆ97.106(9)
ꢇ ˆ102.834(10)
Ê
V ˆ1400.8(2) A
No/range of Refs. used for cell re®nement
Calc. density dx (g/cm3)
Data collection range
26/5.09 < ꢈ < 12.41ꢁ
1.159
3.5 < 2ꢈ < 50ꢁ
Scan type / scan range
No. Total data recorded
No. Unique data
!=1:1ꢁ
6027
4859
Weighting schemea
a ˆ 0:0603; b ˆ 0:3677
No. Obs. / no. parameters
Rb1; wRc2ꢂI > 2ꢉꢂI†
4859 / 334
R1 ˆ 0:0511; wR2 ˆ 0:1270
e.s.d. pf C±C bondlength
0.003
3
Ê
Highest peak in ®nal ÁF map (e Á A
)
0.166
Anisotropic non-H atoms
all
Isotropic non-H atoms
1
none
ꢊ(MoKꢂ) (mm
)
0.073
Ê
Radiation (ꢄ(A))
Transm. factors
0.71073
0.9031 0.7919
P
2
a
1
w
2
ˆ ꢂꢉ2ꢂFo2† ‡ ꢂaP† ‡ bP† where P ˆ ꢂFo2 ‡ 2Fc2†=3; goodness of Fit (GOOF): ꢂ ꢂwꢂFo2
0:5
Fc2† †=ꢂM N†† where M is the number of re¯ections and N is the number of parameters re®ned;
P
P
P
2
2
0:5
b R1 ˆ ꢂ j Fo j j Fc j†= j Fo j; c wR2 ˆ ꢂ ‰ꢂwꢂFo2 Fc2† †=ꢉꢂwꢂFo2† ††

836
M. T. Huggins et al.
300 MHz): 1.09 (t, J ˆ 7:3 Hz, 6H), 2.08 (s, 6H), 2.63 (q, J ˆ 7:3 Hz, 4H), 6.70 (d, J ˆ 4:4 Hz, 2H),
8.58 (br s, 2H) ppm; 13C NMR (CDCl3, ꢃ, 75 MHz): 9.73 (q), 15.04 (q), 17.95 (t), 120.26 (d), 120.36
(s), 128.17 (s), 131.73 (s), 174.44 (s) ppm.
X-Ray structure and solution
Crystals of 2,20-dipyrryl ketone 1 were grown by slow diffusion of MeOH into a solution of CH2Cl2.
Suitable crystals were coated with epoxy cement, mounted on a glass ®ber, and placed on a Siemens
4
3
Ê 2
Table 7. Atomic coordinates (Â10 ) and equivalent isotropic displacement parameters (A Â10 ) for 1
x
y
z
U(eq)a
O(1A)
N(1A)
N(2A)
C(1A)
C(2A)
C(3A)
C(4A)
C(5A)
C(6A)
C(7A)
C(8A)
C(9A)
C(31A)
C(32A)
C(41A)
C(71A)
C(72A)
C(81A)
O(1B)
N(1B)
N(2B)
C(1B)
C(2B)
C(3B)
C(4B)
C(5B)
C(6B)
C(7B)
C(8B)
C(9B)
C(31B)
C(32B)
C(41B)
C(71B)
C(72B)
C(81B)
10608(2)
13093(2)
7065(2)
10148(3)
11253(3)
10794(3)
12412(3)
13788(3)
8494(3)
8065(3)
6331(3)
5761(3)
8946(3)
8104(4)
12600(4)
9269(4)
10484(5)
5297(4)
4082(2)
6373(2)
628(2)
9660(1)
9087(2)
8144(2)
8740(2)
8578(2)
8100(2)
8327(2)
8918(2)
7848(2)
6607(2)
6183(2)
7154(2)
7587(2)
8516(3)
8020(3)
5850(2)
5674(3)
4908(2)
9763(1)
8266(2)
9112(2)
8855(2)
7962(2)
6720(2)
6308(2)
7283(2)
8682(2)
8159(2)
8260(2)
8840(2)
5922(2)
5701(4)
5038(2)
7690(2)
8527(3)
7827(3)
2281(1)
1194(1)
1898(1)
1642(1)
985(1)
48(1)
40(1)
40(1)
35(1)
35(1)
36(1)
43(1)
47(1)
34(1)
38(1)
45(1)
48(1)
45(1)
82(1)
67(1)
52(1)
91(1)
68(1)
45(1)
45(1)
44(1)
35(1)
37(1)
40(1)
47(1)
53(1)
36(1)
39(1)
46(1)
52(1)
48(1)
103(1)
70(1)
53(1)
83(1)
70(1)
73(1)
248(1)
463(2)
1563(1)
1265(1)
1427(1)
1805(2)
489(1)
691(2)
1194(2)
942(2)
1679(2)
1226(2)
7275(1)
6984(1)
6197(1)
6629(1)
6565(1)
6250(1)
6487(2)
6924(2)
5964(1)
5056(1)
4766(1)
5483(2)
5837(2)
6498(2)
6312(2)
4468(1)
3963(2)
3841(2)
3614(3)
4600(3)
4050(3)
5544(3)
6943(3)
2050(3)
1639(3)
99(3)
668(3)
2187(3)
1079(5)
5610(4)
2833(4)
3601(5)
1159(4)
a
U(eq) is de®ned as one third of the trace of the orthogonalized Uij tensor, Ueq ˆ1/3 trace (U)

Structure and Properties of a 2,20-Dipyrryl Ketone
837
P4 diffractometer at room temperature. Unit cell parameters were determined by least squares
analysis of 26 re¯ections with 5.09 < ꢈ < 12.41ꢁ using graphite monochromatized MoKꢂ radiation
ꢁ
Ê
(0.71073 A). 6027 re¯ections were collected between 3.5 < 2ꢈ < 50 yielding 4859 unique re¯ections
(Rint ˆ 0:0247†. The data were corrected for Lorentz and polarization effects. Crystal data are given
in Table 6. Scattering factors and corrections for anomolous dispersion were taken from a standard
source [25]. Calculations were performed using a Siemens SHELXTL PLUS, version 5.03, system of
programs re®ning on F2. The structure was solved by direct methods in the space group P-1. The unit
cell contains two crystallographically unique molecules that lie in an ordered array with no unusual
contacts.
All non-hydrogen atoms (Fig. 3B, Table 7) were re®ned with anisotropic thermal parameters. The
data were corrected using an empirical model derived from É scans. Hydrogen atom positions were
Ê
calculated using a riding model with a C-H distance ®xed at 0.96 A and a thermal parameter of 1.2
times that of the host carbon atom. The largest peak in the ®nal difference map corresponded to
Ê 3
Ê
0.150 e /A and was located 1.2 A from the C81 a carbon. Tables of bond lengths and angles,
anisotropic displacement parameters, and isotropic displacement parameters have been deposited at
the Cambridge Structural Data ®le (CCDC No. 43504).
Acknowledgements
We thank the U.S. National Institutes of Health (HD-17779) for generous support of this work.
Michael T. Huggins is an R.C. Fuson Graduate Fellow. Special thanks are accorded to Prof. V. J.
Catalano for the X-ray crystallographic measurements and to Prof. T. W. Bell for generous use of the
VPO instrument.
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Received February 4, 2000. Accepted February 14, 2000