Sterically crowded heterocycles. XII. Atropisomerism of (1-aryl-3,5-diphenyl-1H-pyrrol-2-YL)(phenyl)methanones

Article abstract of DOI:10.1135/cccc20000651

Some 1-(2-substituted phenyl)-and 1-(1-naphthyl)-2,4,6-triphenylpyridinium perchlorates were treated with potassium hexacyano ferrate(III)-potassium hydroxide reagent to give the title pyrroles. Restricted rotation around the C-N bond in the products is demonstrated by NMR experiments with homochiral shift reagents, by semiempirical PM3 calculations as well as using their atropodiastereoselective and enantioselective transformations. Racemisation barriers for the (R)-2-(N-methyl-N-phenylcarbamoyl) derivative were estimated from NMR and polarimetric measurements.

Full text of DOI:10.1135/cccc20000651

Sterically Crowded Heterocycles
651
STERICALLY CROWDED HETEROCYCLES. XII. ATROPISOMERISM
OF (1-ARYL-3,5-DIPHENYL-1H-PYRROL-2-YL)(PHENYL)METHANONES
a
a
c1
Robert KLVAŇA , Radek POHLa1, Jan PAWLAS , Jan ČEJKAb1, Hana DVOŘÁKOVÁ ,
Richard HRABAL , Stanislav BÖHMa2,*, Bohumil KRATOCHVÍL
and Josef KUTHAN
c2
b2
a
a
Department of Organic Chemistry, Prague Institute of Chemical Technology, 166 28 Prague 6,
Czech Republic;e-mail: radek.pohl@vscht.cz, bohm@vscht.cz
Department of Solid State Chemistry, Prague Institute of Chemical Technology, 166 28 Prague 6,
Czech Republic;e-mail: cejka@vscht.cz, bohumil.kratochvil@vscht.cz
Laboratory of Nuclear Magnetic Resonance, Prague Institute of Chemical Technology,
166 28 Prague 6, Czech Republic;e-mail: hana.dvorakova@vscht.cz, richard.hrabal@vscht.cz
1
2
b
c
1
2
1
2
Received Decem ber 21, 1999
Accepted February 16, 2000
Dedicated to Professor Otakar Červinka on the occasion of his 75th birthday.
Som e 1-(2-substituted ph en yl)- an d 1-(1-n aph th yl)-2,4,6-triph en ylpyridin ium perch lorates
were treated with potassium h exacyan o ferrate(III)–potassium h ydroxide reagen t to give th e
title pyrroles. Restricted rotation aroun d th e C–N bon d in th e products is dem on strated by
NMR experim en ts with h om och iral sh ift reagen ts, by sem iem pirical PM3 calculation s as well
as usin g th eir atropodiastereoselective an d en an tioselective tran sform ation s. Racem isation
barriers for th e (R)-2-(N-m eth yl-N-ph en ylcarbam oyl) derivative were estim ated from NMR
an d polarim etric m easurem en ts.
Key w ord s: Pyrroles; Pyridin ium salts; Atropisom erism ; Axial ch irality; Biaryls; Racem -
isation ; Sem iem pirical calculation s; X-Ray diffraction .
Alm ost twen ty years ago an origin al pyrrole syn th esis h as been discovered1
in our laboratory. Th is approach is based on th e ferricyan ide oxidation of
1-substituted 2,4,6-triarylpyridin ium salts an d h as been later gen eralised2
for preparation of various pyrrole derivatives. In th is way, 1-aryl-
2,3,5-trisubstituted pyrroles are easily accessible, wh ich m ay exh ibit
atropisom erism on th e C(sp2)–N(sp2) bon d as reported in a recen t prelim i-
n ary com m un ication 3.
On ly lim ited exam ples of th e C(sp2)–N(sp2) atropisom erism in five-
m em bered h eterocyclic m olecules are kn own 4 for several 3-substituted
1-(h et)aryl 2,6-dim eth ylpyrroles. Th us, th e pyrrole 1 (R1 = R3 = CO2H, R2 = H)
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

652
Klvaňa et al.:
was resolved in to its en an tiom ers via diastereoisom eric brucin e salts4a.
Ch iral NMR sh ift reagen ts were used4b to dem on strate atropisom erism of six
ortho-substituted 1-ph en ylpyrroles 1 (R1 = Cl, CN, Me, OMe, OEt, OCH2Ph ;
R2 = H; R3 = CHO) as well as of one ortho,ortho-disubstituted 1-phenylpyrrole 1
(R1 = Cl, R2 = Me, R3 = CHO). Ch iral HPLC tech n iques were successful4b,4c in
detection of en an tiom eric 1-h etarylpyrroles 2 an d 3 or even in separation
of en an tiom ers of com poun ds possessin g bulkier ortho-substituen ts, n am ely
of 1-ph en ylpyrrole 1 (R1 = OCH2Ph , CH2Ph ; R2 = H; R3 = CHO) an d
1-(quin olin -8-yl)pyrrole 4. Th e correspon din g barriers to rotation were esti-
m ated4b,4c to be in th e ran ge from 12.4 to 31.0 kcal/m ol. Sim ilar studies
h ave been reported for atropisom eric N-(2-tert-butylph en yl)-2-m eth yl-
m aleim ide5a and 3-benzyl-1-(2-tert-butylphenyl)-5-m ethoxym ethyl-2-pyrrol-
idone5b.
R3
CHO
CHO
CHO
Me
Me
Me
N
Me
Me
N
Me
Me
R2
Me
R1
N
N
N
N
N
N
N
N
Me
4
3
2
1
In th e start of th is paper th e kn own procedure2a of th e ferricyan ide oxida-
tion of 5a to 6a h as been exten ded to oth er quatern ary pyridin ium salts
5b–5f (Sch em e 1) wh ich gave th e expected n ew pyrrole derivatives 6b–6f in
Ph
Ph
Ph
3
4
ClO4
Ph
OH
R1
5
2
1
N
Ph
R4
COPh
Ph
R4
N
Ph
R4
N
Ph
R1
Φ
H
R1
LiAlH4
K3[Fe(CN)6]
KOH
R2
R2
R2
R3
R3
R3
6
9
5
5,6,9
R1
H
Me
Me
Me
R2
H
H
Me
H
H
R3
H
H
H
Me
H
R4
H
H
H
Me
H
a
b
c
d
e
f
MeO
CO2H
H
H
H
SCHEME 1
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Sterically Crowded Heterocycles
653
satisfactory yields. An alogously, 1-(1-n aph th yl) substituted pyridin ium salt
7 afforded th e correspon din g pyrrole 8 (Sch em e 2).
Ph
Ph
COPh
Ph
H
ClO4
Ph
Ph
OH
Ph
Ph
N
N
N
Ph
Φ
LiAlH4
K3[Fe(CN)6]
KOH
8
10
7
SCHEME 2
Th e expected atropisom erism of keton es 6a–6e an d 8 h as been in vesti-
gated by 1H NMR usin g th e ch iral sh ift reagen t europium tris[3-(h epta-
fluoropropylh ydroxym eth ylen e)-(+)-cam ph orate] [(+)-Eu(h fc)3] in C6D6 so-
lution s. As follows from Table I, on ly 2-substituted derivatives 6b, 6c, 6e
an d 1-n aph th yl derivative 8 exh ibit typical 1 : 1 splittin g of th e proton sin -
glet sign als in dicatin g th e racem ic n ature of th e com poun ds wh ile th e par-
en t ph en yl derivative 6a an d 2,4,6-trim eth ylph en yl derivative 6d do n ot
sh ow th e presen ce of en an tiom ers due to th eir m olecular sym m etry.
In addition to th ese fin din gs, reduction s of keton es 6a–6e an d 8 to corre-
spon din g secon dary alcoh ols 9a–9e an d 10 h ave been attem pted as a ch em -
ical axial ch irality probe con firm ed earlier for sterically crowded
im idazo[1,2-a]h eteroarom atic m olecules6. In agreem en t with th e above
TABLE I
Ch em ical sh ifts (δ, ppm ) of selected sin glet sign als in 1H NMR spectra (400 MHz, C6D6 solu-
tion s) of com poun ds 6a–6e an d 8 in th e presen ce of (+)-Eu(h fc)3
a
b
Com poun d
CH-4
CH3
CH3
6a
6b
6c
6d
6e
8
6.81
7.04
6.87
6.73
6.87
6.90
–
–
–
2.06
2.17
–
–
–
–
–
7.06
6.88
–
2.05
2.13
2.03
3.31
–
1.83
2.27
–
1.86
–
6.88
6.92
3.33
–
–
–
–
a
b
In th e substituen t R1; in th e substituen ts R2 or R3.
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

654
Klvaňa et al.:
m en tion ed 1H NMR data, LiAlH4 reduction s were foun d to proceed
atroposelectively on ly with th e racem ic substrates 6a–6c, 6e an d 8 leadin g
to atropodiastereoisom eric m ixtures of alcoh ols 9a–9c, 9e an d 10 from
wh ich m ajor stereoisom ers could be isolated as in dividuals. Expectedly, th e
LiAlH4 reduction s of n on -atropisom eric keton es 6a an d 6d gave on ly in di-
vidual alcoh ols 9a an d 9d .
Atropisom erism of acid 6f h as been in vestigated by several ch em ical an d
ph ysical procedures. Th us, its con version with DCC to correspon din g
atropodiastereoisom eric an h ydrides 11 an d 12 dem on strates th e axial
ch irality of th e startin g com poun d 6f. Relative con figuration s of th e prod-
1
ucts, of racem ate 11 an d m esoform 12 were assign ed by H NMR usin g th e
chiral chem ical shift reagent. For 12, a clearly separated doublet at δ 7.82 ppm
presen t in th e C6D6 solution s of th e both stereoisom ers is sh ifted on ly to δ
7.89 ppm after addition of (+)-Eu(h fc)3 wh ile it is splited in to two sign als at
δ 7.75 an d 7.98 ppm for th e racem ate 11 in dicatin g th e presen ce of th e two
en an tiom ers 11a an d 11b.
It m ay be n oted it is a n ew exam ple related to th e kn own 7 ortho-lin ked
atropodiastereoisom eric dipyrrylaren es 13 in wh ich th e bridge A in volves
eith er a meta-attach m en t (A = 3,3-dim eth ylbiph en yl-1,3-ph en ylen e, R = H)7a
or para- an d para,para-attach m en ts (A = 2,5-dim eth yl-1,4-ph en ylen e, R = H
(ref.7a) an d A = 3,3′-dim eth ylbiph en yl-4,4′-diyl, R = Et (ref.7b)). Th e auth ors7
h ave assign ed th e racem ic structure to th e h igh er m eltin g an d less soluble
meta-lin ked atropodiastereoisom er7a but th e meso con figuration to th e para-
an d para,para-lin ked atropodiastereoisom ers7a,7b. In our case m ore soluble
(polar) but lower m eltin g atropodiastereoisom er 11 is actually racem ic.
R2
R3
R4
CO
ROCO
Me
R6
R7
R8
COOR
Me Me
A
N
N
13
R1
R5
CO
Me
R6
N
N
O
R1
Ph
R2
H
R3 R4
R5
R7 R8
Ph
H
H
PhCO PhCO Ph
H
11a
11b
12
PhCO Ph
Ph
Ph
Ph
H
H
Ph PhCO
Ph PhCO
11, 12
H
Ph PhCO Ph
An addition al proof of racem ic n ature of th e acid 6f is its con version by
DCC m eth od with (R)-1-ph en yleth ylam in e to a ca 1 : 1 m ixture of two
atropodiastereoisom eric am ides 14 an d 15. Absolute con figuration s of th e
both products were determ in ed by th e X-ray diffraction an alysis of th e
h igh er m eltin g stereoisom er to wh ich form ula 14 could be assign ed (Fig. 1).
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Sterically Crowded Heterocycles
655
Th e opposite an d stron gly differen t optical rotation s foun d for th e
atropodiastereoisom ers 14 an d 15 ([α]D +54.5 an d –124.9) suggest th at th e
stron gly differen t data, eviden tly in fluen ced in by m utual con figuration s
with in th e 1-ph en yl-pyrrolic π-electron ic system s, m igh t be a useful ch arac-
teristic in our future in vestigation s of absolute stereoch em istry of th e 6-like
com poun ds.
Ph
COPh
CONH
Ph
COPh
CONH
Ph
Ph
N
Me
N
Me
Φ
H
H
Ph
Ph
14
15
Con figuration al stability of com poun ds 6a–6d , 6f an d 8 h as also been in -
vestigated by quan tum ch em ical calculation s of rotation barriers usin g th e
PM3 m eth od8a an d an earlier reported procedure8b. From Table II, wh ere
th e sym bols ΦS, ΦATS1 an d ΦATS2 den ote torsion an gles of (S)-en an tiom ers
an d in th e pairs of approxim ate tran sition states8c, it follows th at
n on -atropisom eric 1-ph en ylpyrrole 6a exh ibits low barriers to rotation
aroun d various bon ds (1.2–6.2 kcal/m ol) an d represen ts th e case with out
FIG. 1
Th e ORTEP drawin g of am ide 14
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

656
Klvaňa et al.:
an y h ope of detectin g rotation al isom ers un der usual con dition s. Th e sec-
on d n on -atropisom eric 1-(2,4,6-trim eth ylph en yl)pyrrole 6d con tain s th e
aryl group alm ost in capable to rotate (39.6–43.4 kcal/m ol) but th e corre-
spon din g torsion an gle Φ = 90° excludes an y axis ch irality iden tical with
th e N–C(sp2) bon d. On th e oth er h an d, th e PM3 m odels of all
atropisom eric 1-arylpyrroles 6b, 6c, 6f an d 8, exh ibit th e correspon din g ro-
tation barriers with in th e ran ge from 19.3 to 27.1 kcal/m ol, th us supportin g
th e expected type of axial ch irality.
An an alogous approach to th e PM3 calculation s of th e tran sform ation
barriers between atropodiastereoisom ers 14 an d 15 did n ot turn out to be
un ique because of th e con form ation al flexibility of th e side ch ain s associ-
ated with sm all ch an ges in m olecular en ergy. Th us, th e first en ergy m in i-
m um of th e ∆Hf = f(Φ) curve correspon ds to th e anti-con form er of 14 (with
respect to m utual space orien tation of both C=O bon ds) but th e atropodia-
stereoisom erisation anti-14 → 15 represen ted by a stepwise in crease in th e
torsion an gle Φ results in syn-con form er of 15. Sim ilarly, after th e tran sfor-
m ation of syn-15 to anti-15 (by sm all Φ variation s an d subsequen t en ergy
optim isation ), th e reverse atropisom erisation procedure anti-15 → 14 re-
sults in syn-con form er of 14. Th ese facts suggest th at
a deeper
con form ation al ch an ges m ay be expected in th e m utual atropo-
diastereoisom erisation s of 14 an d 15.
TABLE II
Calculated rotation barriers ∆E1,2, un certain ties in h eats of form ation δ∆Hf (kcal/m ol) an d
torsion an gles Φ (±5°)a calculated by th e PM3 m eth od
Molecule
Bon d
∆E1
∆E2
δ∆Hf
ΦS
ΦATS1
ΦATS2
6a
N1–Ar
C2–CO
C3–Ph
C5–Ph
OC–Ph b
N1–Ar
N1–Ar
N1–Ar
C2–CO
N1–Ar
N1–Ar
4.6
3.8
4.8
6.2
+0.1
+0.2
0.0
70
70
0
0
180
180
180
150
–
1.4
1.4
60
0
1.2
1.3
+0.1
–
120
130
90
0
2.0
–
60
20
20
30
0
6b
6c
6d
24.0
22.0
43.4
4.6
19.3
21.2
39.6
6.0
+0.3
–0.4
–0.01
+0.4
–0.9
–0.1
190
190
200
190
200
200
110
90
60
6f
8
21.4
27.1
20.2
22.8
70
20
35
90
a
b
Φ ch an gin g from 0 to 360°; th e h igh est barrier on ly.
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Sterically Crowded Heterocycles
657
As sh own in Table III, com plete m olecular geom etry optim isation s with
respect to all degrees of freedom lead to syn- an d anti-con form ers of 14 an d
15 possessin g very sim ilar h eats of form ation . In fact, a real n um ber of all
con form ers of am ides 14 an d 15 m igh t be h ardly accessible by th e sim ple
procedure8b. Hen ce, on ly th e en ergy barriers ∆E1,2 = 25.4–29.4 kcal/m ol for
th e selected tran sform ation s anti-14 → syn-15 an d anti-15 → syn-14 could
be calculated an d com pared with experim en tal activation Gibbs en ergies
1
∆G‡ obtain ed by H NMR an d polarim etric m easurem en ts of am ides 14 an d
15 m utually isom erised in solution at th e tem peratures 363 to 396 K.
Th e experim en tal barriers ∆G‡ given in Table IV were obtain ed in two dif-
feren t ways. A m ore accurate approach was based on kin etic m easurem en ts
TABLE III
Heats of form ation ∆Hf an d selected isom erisation barriers ∆E1,2 calculated by th e PM3
m eth od (in kcal/m ol)
a
Con form er
∆Hf
Isom erisation
∆E1
∆E2
anti-14
syn-14
anti-15
syn-15
87.5
89.5
89.5
86.2
anti-14 → syn-15
29.4
28.8
anti-15 → syn-14
25.4
25.7
a
Min im ised with respect to all geom etry degrees of freedom .
TABLE IV
Kin etic an d th erm odyn am ic data for th e isom erisation s 14 → 15 an d 15 → 14
T, K
k1, s–1 10–5
k2, s–1 10–5
∆G*, kcal m ol–1
K
∆G0, cal m ol–1
363b
380b
380c
396c
4.22
17.44
6.25
5.25
20.77
6.25
28.6; 28.5
29.0; 28.8
29.7 ± 0.1
30.4 ± 0.1
0.804
0.840
1d
157.2
131.6
–
–
13.90
13.90
1d
a
c
b
For th e m ean in g of th e sym bols, see Experim en tal; by 1H NMR in DMSO-d6 solution s;
d
polarim etric determ in ation for diglym e solution s; approxim ation for rough ly en an tio-
m eric structures, see ref.10b
.
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

658
Klvaňa et al.:
of th e isom erisation 14 → 15 in DMSO-d6. It started from atropodiastereo-
isom er 14 an d proceeded to th e equilibrium m ixtures of 14 an d 15 bein g
m on itored by in tegral in ten sities of m eth yl doublets in 1H NMR spectra at
δ 0.67 (14) an d 1.37 (15) ppm . An altern ative kin etic procedure con siderin g
both atropodiastereoisom ers 14 and 15 to be roughly enantiom eric was based
on polarim etric m easurem ents during the opposite isom erisations 15 → 14 in
diglym e. In all cases com parable ∆G‡ values with in th e ran ge from 28.5 to
30.4 kcal/m ol were obtain ed (Table IV) bein g n ot so far from th e above
m en tion ed th eoretical ∆E1,2 data given in Table III.
EXPERIMENTAL
Th e tem perature data are un corrected. Meltin g poin ts were determ in ed on a Boetius block.
IR spectra (ν, cm –1; CHCl3 solution s) were m easured on a FTIR spectrom eter Nicolet 740.
NMR spectra (δ, ppm ; J, Hz) were m easured on a Varian GEMINI 300HC an d on a Bruker
AM400 an d DRX 500 Avan ce in strum en ts at 297 K. HPLC an alyses were perform ed usin g an
LCP 4000 pum p an d an LCD 2082 UV/VIS detector an d Nucleosil C-18 Mach erey–Nagel col-
um n , m obile ph ase was CH3OH–H2O (8 : 2 or 7 : 3). Com m ercial Silufol plates (Kavalier,
Sázava, Czech Republic) were used for TLC. Optical rotation was m easured on an OPTON
polarim eter usin g a 10 cm cuvette at 293 K, specific rotation s are given in deg cm 3/g l. Th e
X-ray an alysis was perform ed on an En raf CAD4 diffractom eter. Th e sam ples for elem en tal
an alyses were dried in vacuum for 4–20 h , som e at th e toluen e boilin g poin t, an d an alysed
on a Perkin –Elm er 240 C autom atic an alyser. Ch lorin e con ten ts were determ in ed poten tio-
m etrically on a m ercury an d calom el Ba(NO3)2 electrodes.
1-Aryl-2,4,6-triph en ylpyridin ium Perch lorates 5a–5f an d 7
Th e kn own procedures9 were used for preparation of th e perch lorates 5a (m .p. 271–273 °C),
5b (m .p. 252–254 °C), 5e (m .p. 244–246 °C), 5f (263–265 °C) an d 7 (m .p. 282–283 °C).
1-(2,3-Dimethylphenyl)-2,4,6-triphenylpyridinium perchlorate (5c). 2,3-Dim eth ylan ilin e
(1.82 g, l5 m m ol) was added to a refluxed solution of 2,4,6-triph en ylpyrylium perch lorate9c
(5 g, 12 m m ol) in eth an ol (100 m l). After coolin g th e precipitated salt 5c was filtered off
an d recrystallised from eth an ol. Yield 5.79 g (94%), m .p. 282–283 °C. 1H NMR (CDCl3):
1.80 s, 3 H (CH3-2′); 2.01 s, 3 H (CH3-3′); 6.90–7.90 m , 18 H; 8.05 s, 2 H (H-3 and H-5). 13C NMR
(CDCl3): 15.74 CH3; 20.46 CH3; 126.76 2 CH (C-3 an d C-5); 128.25 CH; 128.97 CH; 129.26
CH; 130.00 CH; 130.34 CH; 131.08 CH; 132.27 2 C; 132.36 CH; 133.25 C; 135.20 C; 138.70
C; 139.03 C; 157.34 2 C (C-2 an d C-6); 158.60 C (C-4). For C31H26ClNO4 (512.0) calculated:
72.72% C, 5.12% H, 6.92% Cl, 2.74% N; foun d: 72.82% C, 5.13% H, 7.09% Cl, 2.54% N.
1-(2,4,6-Trimethylphenyl)-2,4,6-triphenylpyridinium perchlorate (5d ). 2,4,6-Trim eth ylan ilin e
(2.5 g, 18 m m ol) was added to a suspen sion of 2,4,6-triph en ylpyrylium perch lorate9c (5 g,
12 m m ol) in eth an ol (100 m l) an d th e m ixture was h eated for 1 h . After coolin g, th e
sligh tly brown ish crystals were precipitated an d recrystallisation from eth an ol afforded 5.6 g
(87%) perch lorate 5d , m .p. 258–261 °C. 1H NMR (CDCl3): 1.96 s, 6 H (2′-CH3 an d 6′-CH3);
2.13 s, 3 H (4′-CH3); 6.69 s, 2 H (H-3′an d H-5′); 7.23–8.00 m , 15 H; 8.14 s, 2 H (H-3 an d
H-5). 13C NMR (CDCl3): 19.24 (CH3-2′ an d CH3-6′); 21.66 (CH3-4′); 127.74 2 CH (C-3 an d
C-5); 129.31 4 CH; 129.50 CH; 129.82 CH; 130.43 CH; 130.54 CH; 131.77 CH; 132.55 2 C;
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Sterically Crowded Heterocycles
659
133.24 CH; 134.40 C; 134.59 C; 135.36 C; 141.86 2 C (C-2′an d C-6′); 157.17 2 C (C-2 an d
C-6); 158.86 C (C-4). For C32H28ClNO4 (526.0) calculated: 73.07% C, 5.37% H, 6.74% Cl,
2.66% N; foun d: 72.78% C, 5.57% H, 7.01% Cl, 2.61% N.
Ferricyan ide Oxidation of Perch lorates 5a–5f an d 7. Gen eral Procedure
Suspen sion of a given perch lorate (1 m m ol) in eth an ol (50 m l) was stirred un der h eatin g
an d th en a solution of potassium ferricyan ide (4 m m ol) an d potassium h ydroxide (8 m m ol)
in water (25 m l) was added dropwise. After 1 h , th e reaction m ixture was cooled an d poured
on to crash ed ice an d extracted with dich lorom eth an e. Th e collected extracts were dried with
m agn esium sulfate, HPLC-an alysed, evaporated an d th e residue was recrystallised from eth a-
n ol. Th e earlier described1b pyrroles 6a (m .p. 177–178 °C) an d 6d (m .p. 170–172 °C) were
obtain ed by th e procedure from perch lorates 5a an d 5d in th e yields of 84 an d 88%, respec-
tively.
[1-(2-Methylphenyl)-3,5-diphenyl-1H-pyrrol-2-yl](phenyl)methanone (6b). Th e oxidation of per-
ch lorate 5b (3 g, 20 m m ol) gave wh ite crystals of keton e 6b (2.0 g, 83%), m .p. 162–163 °C.
For IR, 1H NMR an d 13C NMR spectra, see ref.3. For C30H23NO (413.2) calculated: 87.14% C,
5.61% H, 3.39% N; foun d: 87.24% C, 6.12% H, 3.42% N.
[1-(2,3-Dimethylphenyl)-3,5-diphenyl-1H-pyrrol-2-yl](phenyl)methanone (6c). Th e oxidation of
perch lorate 5c (2 g, 3.9 m m ol) gave yellowish crystals of keton e 6c (1.4 g, 84%), m .p.
166–168 °C. IR: 1 628 (C=O). 1H NMR (CDCl3): 1.84 s, 3 H (CH3-2′); 2.19 s, 3 H (CH3-3′);
6.64 s, 1 H (H-4); 7.00–7.26 m , 16 H; 7.60 m , 2 H (H-ortho in COPh ). 13C NMR (CDCl3):
14.79 CH3; 20.76 CH3; 111.29 CH (C-4); 125.98 CH; 127.05 CH; 127.87 CH; 128.16 CH;
128.24 2 CH; 128.50 2 CH; 128.80 2 CH; 129.05 2 CH; 129.96 2 CH; 130.60 CH; 130.64
2 CH; 130.94 C; 132.52 CH; 132.58 C; 133.59 C; 135.61 C; 136.01 C; 138.25 C; 138.85 C;
139.29 C; 140.39 C; 180.57 C (CO). For C31H25NO (427.6) calculated: 87.00% C, 5.89% H,
3.28% N; foun d: 86.75% C, 6.20% H, 3.18% N.
[1-(2-Methoxyphenyl)-3,5-diphenyl-1H-pyrrol-2-yl](phenyl)methanone (6e). Th e oxidation of
perch lorate 5e (1.2 g, 2.4 m m ol) gave wh ite crystals of keton e 6e (0.73 g, 71%), m .p.
211–213 °C. IR: 1 628 (C=O). 1H NMR (CDCl3): 3.49 s, 3 H (CH3O-2′); 6.63 s, 1 H (H-4);
6.82–7.30 m , 17 H; 7.66 m , 2 H (H-ortho in COPh ). 13C NMR (CDCl3): 55.91 CH3O; 111.38
CH (C-4); 112.35 CH; 121.35 CH; 121.26 CH; 127.03 CH; 127.16 CH; 128.08 CH; 128.23
2 CH; 128.52 2 CH; 128.68 C; 128.73 2 CH; 129.38 2 CH; 129.94 CH; 130.02 2 CH; 130.54
CH; 130.79 2 CH; 132.48 CH; 132.83 C; 132.99 C; 136.07 2 C; 139.26 C; 139.65 C; 155.39
C; 188.95 C (CO). For C30H23NO2 (429.5) calculated: 83.89% C, 5.40% H, 3.26% N; foun d:
84.14% C, 5.59% H, 3.12% N.
2-(2-Benzoyl-3,5-diphenyl-1H-pyrrol-1-yl)benzoic acid (6f). In th e oxidation of perch lorate 5f
(3.3 g, 6.3 m m ol) th e reaction m ixture was h eated for 3 h an d after pourin g in to crush ed ice
acidified with 1 M HCl to pH 5. Th e crude product was purified by colum n ch rom atograph y
(200 g silica gel, dich lorom eth an e–eth an ol 98 : 2) an d crystallisation from h eptan e–eth an ol
3 : 1. Yield 1.56 g (56%) of carboxylic acid 6f, yellow crystals, m .p. 204–205 °C. IR: 1 625
(C=O, keton e); 1 701 an d 1 795 (C=O, carboxylic). 1H NMR (CDCl3): 6.62 s, 1 H (H-4);
6.96–7.43 m , 16 H; 7.65 d, 2 H, J = 7.1; 7.79 dd, 1 H, J = 1.6 an d 7.7. 13C NMR (CDCl3):
113.31 CH (C-4); 127.75 CH; 128.58 2 CH; 128.70 2 CH; 129.13 3 CH; 129.78 2 CH; 130.02
CH; 130.22 3 CH; 130.60 CH; 131.48 2 CH; 132.30 C; 132.52 CH; 133.76 CH; 134.65 C;
135.19 C; 137.57 C; 137.93 C; 138.03 C; 145.20 C; 169.55 C (CO2H-2′); 190.22 C (COPh ).
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For C30H21NO3 (443.5) calculated: 81.24% C, 4.77% H, 3.16% N; foun d: 81.22% C, 5.20% H,
3.06% N.
[1-(1-Naphthyl)-3,5-diphenyl-1H-pyrrol-2-yl](phenyl)methanone (8). Th e oxidation of per-
ch lorate 7 (3 g, 5.6 m m ol) was perform ed by th e gen eral procedure but th e crude product
was purified by colum n ch rom atograph y (100 g silica gel, petroleum eth er–dich lorom eth an e
1 : 1) prior th e recrystallisation from eth an ol. Yield 2.35 g (93%) of keton e 8, sligh tly yel-
lowish crystals, m .p. 156–158 °C. For IR, 1H NMR an d 13C NMR spectra, see ref.3. For
C
33H23NO (449.6) calculated: 87.77% C, 5.58% H, 3.10% N; foun d: 87.69% C, 5.49% H,
2.99% N.
Reduction of Keton es 6a–6e an d 8. Gen eral Procedure
A solution of a keton e (1 m m ol) in dry dieth yl eth er (12 m l) was stirred an d cooled to
–30 °C un der argon atm osph ere. Th en LiAlH4 (2 m m ol) in dry dieth yl eth er (8 m l) was
added dropwise at th e tem perature n ot exceedin g –25 °C an d th e stirrin g was con tin ued at
–25 to –30 °C for 1 h . After th e startin g keton e was fully con verted to products (TLC, petroleum
eth er–dich lorom eth an e 1 : 1) th e reaction m ixture was decom posed with aqueous 4% NaOH
(4 m l per 1 g LiAlH4), h eated to th e room tem perature, diluted with ben zen e (15 m l) an d fil-
tered. Evaporation of th e filtrates gave con siderably pure products wh ich were, after HPLC
an d 1H NMR an alyses, separated by ch rom atograph y an d/or crystallisation .
(1,3,5-Triphenyl-1H-pyrrol-2-yl)(phenyl)methanol (9a). Th e reduction of keton e 6a (3 g, 7.5
m m ol) gave a wh ite solid th e in dividuality of wh ich (tR = 6.1 m in ) followed from HPLC
(m eth an ol–water 9 : 1) an alysis. Crystallisation from ben zen e–m eth an ol 1 : 1 afforded wh ite
crystals (2.8 g, 92%) of h ydroxy derivative 9a, m .p. 159–162 °C. IR (KBr): 3 549 (OH).
1H NMR (DMSO-d6): 5.88 d, 1 H, J = 3.8 (CCHO); 6.08 d, 1 H, J = 3.8 (OH); 6.60 s, 1 H (H-4);
6.81–7.65 m , 20 H. 13C NMR (DMSO-d6): 65.71 CH (C-OH); 109.83 CH (C-4); 124.65 C;
125.15 CH; 125.66 CH; 125.93 CH; 126.33 CH; 127.18 CH; 127.65 CH; 128.16 CH; 128.31
CH; 128.67 CH; 132.75 C; 134.03 C; 134.35 C; 136.12 C; 138.64 C; 143.05 C. For C29H23NO
(401.5) calculated: 86.75% C, 5.77% H, 3.49% N; foun d: 86.67% C, 6.16% H, 3.39% N.
Atropodiastereoisomeric [1-(2-methylphenyl)-3,5-diphenyl-1H-pyrrol-2-yl](phenyl)methanol (9b).
Th e reduction of keton e 6b (0.35 g, 0.85 m m ol) gave a wh ite-yellowish solid (m .p. 129–133 °C,
yield 89%) con tain in g two isom ers (tR = 111.6 an d 121.5 m in ) in th e ratio 7 : 3 (HPLC,
m eth an ol–water 7 : 3). For IR an d NMR data, see ref.3. For C30H25NO (415.5) calculated:
86.71% C, 6.06% H, 3.37% N; foun d: 86.36% C, 6.31% H, 3.39% N. A sam ple (200 m g) was
subjected to preparative TLC (15 g of Aldrich h igh -purity silica gel with gypsum bin der
an d fluorescen t in dicator at 254 n m , 20 × 20 cm plates) wh ich after elution (10 tim es)
with petroleum eth er–dich lorom eth an e (5 : 1) gave alm ost pure (>99%) m ajor atropodia-
stereoisom er of 9b (lower RF), wh ite crystals, m .p. 130–134 °C. NMR data are given in ref.3.
Atropodiastereoisomeric [1-(2,3-dimethylphenyl)-3,5-diphenyl-1H-pyrrol-2-yl](phenyl)methanol
(9c). Th e reduction of keton e 6c (0.5 g, 1.17 m m ol) gave a wh ite solid (m .p. 126–132 °C,
yield 94%) as a m ixture of two isom ers (HPLC, m eth an ol–water 4 : 1, two partly overlapped
peaks at 30.9 an d 34.7 m in ) in th e ratio 2 : 1. IR (KBr): 3 542. A part of 1H NMR (DMSO-d6):
0.92 s, 3 H; 1.67 s, 3 H; 1.81 s, 3 H; 2.14 s, 3 H; 6.55 s, 1 H; 6.64 s, 1 H. For C31H27NO
(429.6) calculated: 86.68% C, 6.34% H, 3.26% N; foun d: 86.35% C, 6.72% H, 3.18% N. Th e
preparative TLC perform ed as above afforded alm ost pure (>99%) m ajor atropodia-
stereoisom er of 9c (lower RF), wh ite crystals, m .p. 130–134 °C. 1H NMR (DMSO-d6): 0.92 s, 3 H
(Me); 1.81 s, 3 H (Me); 5.90 m , 2 H (OH an d H-6); 6.58 s, 1 H (H-4); 6.70–7.76 m , 19 H.
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Sterically Crowded Heterocycles
661
13C NMR (DMSO-d6): 13.53 CH3; 19.43 CH3; 65.85 CH (C-6); 108.77 CH (C-4); 124.40 C;
124.78 CH; 125.08 2 CH; 125.41 CH; 126.00 CH; 126.36 CH; 126.80 2 CH; 127.27 2 CH;
128.12 2 CH; 128.12 2 CH; 128.43 2 CH; 128.78 2 CH; 128.94 CH; 129.66 CH; 132.88 C;
133.55 C; 134.67 C; 135.32 C; 136.40 C; 136.52 C; 137.47 C; 142.73 C.
[1-(2,4,6-Trimethylphenyl)-3,5-diphenyl-1H-pyrrol-2-yl](phenyl)methanol (9d ). Th e reduction
of keton e 6d (0.5 g, 1.2 m m ol) resulted in 0.47 g (92%) of crude com poun d 9d (HPLC,
m eth an ol–water 7 : 3, on e peak at 204.8 m in ) givin g by recrystallisation from m eth an ol
wh ite-yellowish crystals, m .p. 129–132 °C. IR (KBr): 3 559 (OH). 1H NMR (DMSO-d6): 1.60 s,
3 H (Me); 2.00 s, 3 H (Me); 2.26 s, 3 H (Me); 5.88 d, 1 H, J = 4.6 (CCHO); 5.86 d, 1 H, J = 4.7
(OH); 6.68 s, 1 H (H-4); 6.68–7.72 m , 18 H. 13C NMR (DMSO-d6): 17.34 CH3; 18.03 CH3;
20.58 CH3; 66.20 CH (C-O); 109.76 CH (C-4); 124.49 C; 125.61 CH; 125.87 2 CH; 125.98
CH; 126.41 CH; 126.63 2 CH; 127.16 2 CH; 127.85 2 CH; 128.35 2 CH; 128.62 CH; 128.70
CH; 128.89 2 CH; 132.32 C; 132.95 C; 133.06 C; 134.42 C; 136.34 C; 137.00 C; 137.20 C;
137.73 C; 143.13 C. For C32H29NO (443.6) calculated: 86.65% C, 6.59% H, 3.16% N; foun d:
86.36% C, 6.65% H, 3.16% N.
Atropodiastereoisomeric [1-(2-methoxyphenyl)-3,5-diphenyl-1H-pyrrol-2-yl](phenyl)methanol
(9e). Th e reduction of keton e 6e (0.3 g, 0.7 m m ol) afforded 0.28 g (88%) of a wh ite-yellowish
m ixture (m .p. 122–152 °C) of two isom ers (HPLC, m eth an ol–water 4 : 1, two peaks at 15.2
an d 19.3 m in ) in th e ratio 3 : 2. IR (KBr): 3 541 (OH). A part of 1H NMR (DMSO-d6): 3.06 s,
3 H; 3.60 s, 3 H; 6.50 s, 1 H; 6.58 s 1 H. For C30H25NO2 (431.5) calculated 83.50% C, 5.84% H,
3.25% N; foun d: 83.08% C, 6.02% H, 3.22% N. A wh ite sam ple en rich ed by th e m ajor
atropodiastereoisom er (>95%), m .p. 149–155 °C, was obtain ed by crystallisation from m eth a-
n ol an d dieth yl eth er–h eptan e. 1H NMR (DMSO-d6): 3.06 s, 3 H (MeO); 5.88 m , 2 H
(CHOH); 6.44 d, 1 H, J = 8.2; 6.58 s, 1 H (H-4); 6.74–7.70 m , 18 H. 13C NMR (DMSO-d6):
54.51 CH3; 65.70 CH (C-O); 108.59 CH (C-4); 111.08 CH; 119.28 CH; 124.56 C; 125.11
2 CH; 125.22 CH; 125.92 CH; 126.27 CH; 126.75 2 CH; 127.15 C; 127.22 2 CH; 127.93
2 CH; 128.45 2 CH; 128.61 2 CH; 129.67 CH; 131.91 CH; 133.14 C; 133.24 C; 135.18 C;
136.53 C; 142.44 C; 154.81 C.
Atropodiastereoisomeric [1-(1-naphthyl)-3,5-diphenyl-1H-pyrrol-2-yl](phenyl)methanol (10). Th e
reduction of keton e 8 (0.5 g, 1.2 m m ol) gave a wh ite-yellowish product, m .p. 165–171 °C
(0.48 g, 94%) exh ibitin g on ly on e broad HPLC peak (m eth an ol–water 4 : 1 an d 7 : 3, 26.3
an d 160.1 m in , respectively) but a couple of th e (H-4) sign als (6.69 s, 1 H an d 6.74 s, 1 H)
in 1H NMR (DMSO-d6) in dicated th e presen ce of two isom ers of 10. IR (KBr): 3 545 (OH).
For C33H25NO (451.6) calculated: 87.77% C, 5.58% H, 3.10% N; foun d: 87.44% C, 6.15% H,
3.18% N. Recrystallisation s from m eth an ol an d dieth yl eth er–h eptan e afforded a sam ple en -
rich ed by on e of th e atropodiastereoisom ers (>90%), m .p. 169–174 °C. 1H NMR (DMSO-d6):
5.86 d, 1 H, J = 3.8 (CHO); 5.93 d, 1 H, J = 3.8 (OH); 6.69 s, 1 H (H-4); 6.44–7.96 m , 22 H.
13C NMR (DMSO-d6): 65.88 CH (C-O); 109.39 CH (C-4); 123.18 CH; 124.70 CH; 124.77 CH;
124.96 CH; 125.75 CH; 126.12 CH; 126.19 CH; 126.44 CH; 126.54 CH; 127.17 CH; 127.44
CH; 128.03 CH; 128.44 CH; 128.86 CH; 129.05 CH; 130.78 C; 132.97 C; 133.13 C; 134.92 C;
135.23 C; 135.63 C; 136.32 C; 142.17 C.
Atropodiastereoisom eric Bis[2-(2-ben zoyl-3,5-diph en yl-1H-pyrrol-1-yl)]ben zoic An h ydrides
11 an d 12
A m ixture of com poun d 6f (1.0 g, 2.26 m m ol) an d DCC (460 m g, 2.26 m m ol) in
dich lorom eth an e (25 m l) was stirred at room tem perature an d HPLC-m on itored (m eth an ol–
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662
Klvaňa et al.:
water 4 : 1, 0.8 m l/m in ). After 30 m in th e precipitated dicycloh exylurea was filtered off an d
th e filtrate con tain in g an h ydrides 11 an d 12 in th e ratio 1 : 3.8 was evaporated in vacuum .
Th e residue was colum n -ch rom atograph ed on silica gel (120 g, toluen e with 0 to 5% gradi-
en t of eth yl acetate).
Min or less polar meso-atropodiastereoisom er 12 (70 m g) was recrystallised from aceton e
givin g yellow crystals, m .p. 207–212 °C. For C60H40N2O5 calculated: 868.9858 (M); HR MS
foun d: 868.2952. IR (CHCl3): 995 an d 1 017 (COC); 1 626 (C=O); 1 734 an d 1 797 (an h y-
dride). 1H NMR (CDCl3): 6.96–7.05 m , 10 H; 7.10–7.22 m , 20 H; 7.36 dd, 2 H, J = 1.6 an d
8.2; 7.41–7.52 m , 4 H; 7.56 d, 4 H, J = 7.1. 13C NMR (CDCl3) : 111.79 2 CH; 126.35 2 CH;
127.48 4 CH; 127.61 4 CH; 127.66 2 CH; 128.14 4 CH; 128.22 2 CH; 129.11 4 CH; 129.43 4 CH;
130.10 2 CH; 131.25 2 CH; 131.70 2 CH; 133.23 2 CH; 134.20 2 C; 135.11 2 C; 138.47 2 C;
140.01 2 C; 140.01 2 C; 140.04 2 C; 159.47 2 C (CO, an h ydride); 187.76 2 C (CO, keton e).
Major racem ic atropodiastereoisom er 11 (372 m g). For C60H40N2O5 calculated: 868.9858;
HR MS foun d: 868.2975) was th en crystallised from m eth yl tert-butyl eth er–aceton e form in g,
in agreem en t with HPLC an alysis, a stable solvate, m .p. 154–158 °C. For C60H40N2O5·0.5
C5H12O·0.5 H2O calculated: 81.41% C, 5.14% H, 3.04% N; foun d: 81.33% C, 5.27% H,
3.06% N. IR (CHCl3): 995 and 1 016 (COC); 1 625 (C=O); 1 732 and 1 797 (anhydride). 1H NMR
(CDCl3): 1.20 s, 9 H (Me3C-solven t); 3.22 s, 3 H (MeO-solven t); 6.97–7.08 m , 20 H;
7.08–7.21 m , 40 H; 7.32 d, 4 H, J = 7.7; 7.43 d, 4 H, J = 7.7; 7.50 d, 4 H, J = 8.2; 7.55 d, 8 H,
J = 7.7. 13C NMR (CDCl3): 26.94 3 CH3 (solven t); 49.41 CH3 (solven t); 111.73 2 CH; 126.34
2 CH; 127.45 4 CH; 127.60 4 CH; 127.66 2 CH; 128.08 4 CH; 128.23 2 CH; 129.09 4 CH;
129.46 4 CH; 130.10 4 CH; 131.27 2 CH; 131.40 2 CH; 131.60 2 CH; 133.36 2 CH; 134.26
2 C; 135.16 2 C; 138.50 2 C; 140.18 2 C; 140.26 2 C; 159.63 2 C (CO, an h ydride), 187.64 2 C
(CO, keton e).
Atropodiastereoisom eric (R)- an d (S)-2-(2-Ben zoyl-3,5-diph en yl-1H-pyrrol-1-yl)-
N-[(R)-1-ph en yleth yl]ben zam ides (14) an d (15)
DCC (116 m g, 0.564 m m ol) an d (R)-1-ph en yleth ylam in e (73 µl, 0.564 m m ol) were added to
com poun d 6f (250 m g, 0.564 m m ol) in dich lorom eth an e (8 m l) an d th e reaction m ixture
was stirred at room tem perature for 24 h . Th e m ain fraction of th e precipitated
dicycloh exylurea was filtered off an d th e filtrate was evaporated in vacuum . Th e residue was
dissolved in a m in im um of dich lorom eth an e an d im purities were rem oved by a preparative
TLC (toluen e–eth yl acetate 9 : 1, six tim es developed). Th e resultin g m ixture (ca 1 : 1) of
am ides 14 an d 15 (261 m g, yield 85%, HPLC detection ) was fu rth er su bm itted to TLC
(toluen e–eth yl acetate 91 : 9) by repeated separation of yellowish zon es. Th e fraction con -
tain in g less polar (S,R)-am ide 14 was crystallised from aceton e–h eptan e (1 : 6) affordin g yel-
lowish crystals (85 m g), m .p . 170–174 °C an d [α ]D +54.5 (CHCl3), wh ich were X-ray
an alysed. 1H NMR (CDCl3): 1.16 d, 3 H, J = 6.6 (Me); 5.08 qd, 1 H, J = 6.6 an d 7.7 (NCH);
6.65 s, 1 H (H-4); 7.03–7.44 m , 21 H; 7.60–7.72 m , 2 H; 8.09 d, 1 H, J = 7.7 (NH). 13C NMR
(CDCl3): 22.49 CH3 (Me); 48.95 CH (HCN); 111.41 CH; 126.15 2 CH; 126.77 CH; 127.08
CH; 127.88 2 CH; 127.96 2 CH; 128.16 CH; 128.25 2 CH; 128.31 CH; 128.52 2 CH; 128.82 2
CH; 129.11 CH; 129.24 2 CH; 129.39 CH; 130.13 2 CH; 132.82 CH; 134.20 C; 134.67 C;
135.98 C; 137.12 C; 137.65 C; 141.86 C; 143.26 C; 165.69 C (NCO); 189.21 C (Ph CO). For
C
38H30N2O2 (546.6) calculated: 83.49% C, 5.53% H, 5.13% N; foun d: 83.87% C, 5.89% H,
5.15% N.
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663
Th e fraction con tain in g m ore polar (R,R)-am ide 15 was again TLC separated an d after
crystallisation from ben zen e–h exan e yielded a yellow product (60 m g), m .p. 137–138 °C an d
[α]D –124.9 (CHCl3). 1H NMR (CDCl3): 1.51 d, 3 H, J = 7.1 (Me); 5.15 qd, 1 H, J = 7.1 an d
7.7 (NCH); 6.48 s, 1 H (H-4); 6.91–7.42 m , 21 H; 7.64–7.74 m , 2 H; 8.56 d, 1 H; J = 7.7 (NH).
13C NMR (CDCl3): 22.44 CH3 (Me); 49.10 CH (HCN); 111.71 CH; 125.87 2 CH; 126.67 CH;
126.71 CH; 127.81 2 CH; 128.00 2 CH; 128.12 CH; 128.31 2 CH; 128.98 2 CH; 129.06 CH;
129.28 2 CH; 129.54 CH; 130.11 CH; 130.31 2 CH; 132.72 CH; 134.54 C; 135.01 C; 135.73 C;
137.39 C; 137.62 C; 165.90 C (NCO); 189.21 C (Ph CO). For C38H30N2O2 (546.6) calculated:
83.49% C, 5.53% H, 5.13% N; foun d: 83.58% C, 5.72% H, 5.09% N.
TABLE V
Data collection an d structure refin em en t param eters
Crystal dim en ion s, m m
0.18 × 0.25 × 0.56
Difractom eter an d radiation used, Å
En raf–Non ius CAD4,
λ(CuKα) = 1.54184
Scan tech n ique
ω/1θ
Tem perature, K
293
No. an d θ ran ge of reflection s for lattice param eter refin em en t, °
Ran ge of h, k an d l
20; 38–40
0→9, –20→–20,
–13→13
Stan dard reflection s m on itored in th e in terval; in ten sity fluctuation ,
m in ; %
60; 2.08
Total n um ber of reflection s m easured; 2θ ran ge, °
No. of observed reflection s
5 959; 4–140
2 804
Criterion for observed reflection s
Fun ction m in im ised
I ≥ 1.96σ(I)
w(|Fo| – |Fc|)2
Weigh ten in g sch em e
Ch ebych ev polyn o-
m ial (ref.11
379
)
Param eters refin ed
0.0868, 0.0588,
0.8479
Value of R, wR an d S
Ratio of m ax. least squares sh ift to e.s.d. in th e last cycle
Max. an d m in . h eigh ts in fin al ∆ρ m ap, e Å–3
Program used
0.001
0.38, –0.71
CRYSTALS (ref.12a),
SIR92 (ref.12b),
ORTEP (ref.12c
)
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664
Klvaňa et al.:
Kin etic Measurem en ts
More accurate activation barriers ∆G‡ were obtain ed by m on itorin g th e ch an ges in th e in te-
gral in ten sities of m eth yl doublet sign als at δ 0.67 (14) an d 1.37 (15) ppm in th e 1H NMR
spectrum of th e solution s of am ide 14 in DMSO-d6 at 90 an d 107 °C usin g th e first-order
rate equation 10a –d[14]/dt = (k1 + k2)[14] – K[14]0, wh ere [14]0 an d [14] are startin g an d actual
con cen tration s of th e substrate, k1 an d k2 are th e rate con stan ts for th e processes 14 → 15 an d
15 → 14, an d K is th e correspon din g equilibrium con stan t. For calculation of altern ative
pseudoracem isation barrier ∆G‡ of am ides 14 an d 15 (k1 ÷ k2), ch an ges in th e [α]D values of
th e diglym e solution s of startin g am ide 15 at 107 an d l23 °C were polarim etrically m on i-
tored. Th e rate expression 10b t–1 ln ([15]0/[15]0 – 2 [15]) = 2k for reversible first-order
isom erisation , wh ere [15]0 is th e startin g con cen tration an d [15] con cen tration at tim e t. All
obtain ed data are sum m arised in Table IV.
anti-14
syn-14
syn-15
anti-15
FIG. 2
Con form ers of am ides 14 an d 15 optim ised by th e PM3 m eth od (see text)
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Sterically Crowded Heterocycles
665
X-Ray Diffraction An alysis of Am ide 14
C38H30N2O2, Mf = 546.67, m on oclin ic system , space group P21 (No. 4), a = 8.0820(6) Å, b =
16.5282(8) Å, c = 11.4254(3) Å, β = 103.423(4)°, V = 1 484.5(1) Å3, Z = 2, Dcalc = 1.22 g/cm 3,
µ(CuKα) = 0.59 m m –1, F(000) = 576. Th e structure 14 was solved by direct m eth ods. All of
n on -H atom s were refin ed an isotropically by full m atrix least-squares m eth od based on F val-
ues. Th e h ydrogen atom s were placed respectin g th e ideal geom etry an d fixed in distan ce of
1.0 Å to th e attach ed atom . Th e Friedel pairs were m erged. Structure refin em en t param eters
are listed in Table V. Crystallograph ic data for th e structure of am ide 14 reported in th is pa-
per h as been deposited with th e Cam bridge Crystallograph ic Data Cen tre as supplem en tary
publication n um ber CCDC-139914. Copies of th e data can be obtain ed free of ch arge on ap-
plication to CCDC, e-m ail: deposit@ccdc.cam .ac.uk.
Calculation s
All h eats of form ation ∆Hf were calculated by th e sem iem pirical PM3 m eth od8a an d th e ap-
proxim ate procedure8c was used to calculate barriers to in tram olecular rotation s ∆E1 an d
∆E2. In addition to th e en ergy data, th e torsion an gles for (S)-en an tiom ers ΦS, as well as for
pairs of approxim ate tran sition states ΦATS1 an d ΦATS2 are given in Table II. Th e PM3 m odels
of con form ers anti-14, syn-14, syn-15 an d anti-15 (Fig. 2) correspon din g to m in im a on th e
∆Hf = f(Φ) curves were addition ally optim ised with respect to all geom etrical degrees of free-
dom an d used for th e calculation of th e ∆E1,2 isom erisation barriers sh own in Table III. Th e
con form er anti-14 sh ows to be in good accordan ce with th e structure obtain ed by th e X-ray
diffraction (Fig. 3).
a
b
FIG. 3
Com parison of th e X-ray m olecular skeleton of am ide 14 (a) with th at obtain ed for anti-con -
form er of th e com poun d calculated by th e PM3 m eth od (b)
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

666
Klvaňa et al.:
This project was supported by The Ministry of Education of Czech Republic (Project LB98233). The
authors are indebted to the staff of Central Laboratories (Prague Institute of Chemical Technology) for
elemental analyses.
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