A structure-taste study of arylsulfonyl(cyclo)alkanecarboxylic acids

Article abstract of DOI:10.1016/j.bmc.2004.10.056

A number of sweeteners contain a sulfonyl group. In our current search for new glucophores several new compounds containing such group were obtained. A series of novel 1-phenylsulfonylcyklohexanecarboxylic acids and 2-arylsulfonylalkanecarboxylic acids was obtained and evaluated for their sweet taste quality. It has been found that methyl substituents are of the key importance for the activity of these compounds.

Full text of DOI:10.1016/j.bmc.2004.10.056

Bioorganic & Medicinal Chemistry 13 (2005) 671–675
A structure–taste study of
arylsulfonyl(cyclo)alkanecarboxylic acids
Violetta Lysiak, Aleksander Ratajczak, Agnieszka Mencel,
Krystyna Jarzembek and Jaroslaw Polanski*
Department of Organic Chemistry, Institute of Chemistry, University of Silesia, PL-40-006 Katowice, Poland
Received 13 July 2004; accepted 26 October 2004
Available online 21 November 2004
Abstract—A number of sweeteners contain a sulfonyl group. In our current search for new glucophores several new compounds
containing such group were obtained. A series of novel 1-phenylsulfonylcyklohexanecarboxylic acids and 2-arylsulfonylalkanecarb-
oxylic acids was obtained and evaluated for their sweet taste quality. It has been found that methyl substituents are of the key impor-
tance for the activity of these compounds.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
O
+
K
NH
SO2
O
O
NHSO3H
Synthetic sweeteners are appreciated by industry that
needs such substances for dietary applications. Acesul-
fame K, saccharin, cyclamate (Chart 1) are well known
synthetic sweeteners that are used in large quantity, but
their taste quality are still far from the ideal sucrose
profile.
-
N
S
O
O
Chart 1. Acesulfame K, saccharin, cyclamate.
In our previous researches we have found that some 1-
arylsulfonylalkanecarboxylic acids and 1-aryl-
Designing, discovering, and developing novel active
compounds are far from trivial. Compared to the design
of a new pharmaceutical, which is extremely compli-
cated, developing a new sweetener can be even more dif-
ficult. The reasons for this are quite obvious. The use of
pharmaceuticals is usually restricted to a certain group
of patients that use them in small doses. Frequently,
even if it is in some sense risky, it is better to take them
than to die from the disease. On the contrary, sweeteners
must not only be of excellent taste but they should also
be absolutely safe for the consumption by a wide range
of people. Many different classes of compounds have
been reported to elicit sweet taste. A number of them
contain a sulfonyl group. In particular, similar sulfur
systems can be found especially in sweeteners that are
of commercial importance.
sulfonylcycloalkanecarboxylic acids (ASA) are potent
sweeteners having the activity similar to those of the sac-
charin or aspartame.1 In our current work we concen-
trated on the design and synthesis of new analogs
containing sulfonyl group.
2. Concept of the drug design
The requirements for sweet taste induction have been
deduced by a comparison of different sweetener series
to give several sweet taste receptor models. An early
Shallenberger theory that based sweetness on two-point
concerted hydrogen AH–B bonding2 has been supple-
mented by the KierÕs AH, B, X model3 that involves
the hydrophobic interaction site. A discovery of hyper-
sweeteners brought the Multipoint Attachment Theory
(MPA) of Tinti–Nofre that includes eight interaction
sites, described by B, AH, XH, G1, G2, G3, G4 and
D.4 More recently, several studies attempted to con-
struct multi-class QSAR or QSPR sweetness models.5,6
*
Corresponding author. Fax: +48 32 599978; e-mail: polanski@us.
edu.pl
0968-0896/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmc.2004.10.056

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V. Lysiak et al. / Bioorg. Med. Chem. 13 (2005) 671–675
On the other hand, a structure of the sweet taste recep-
tor has been described as a polypeptide chain having se-
ven transmembrane domain segments, TMI–TMVII
which form a pocket in which sweet ligands are
bound.7,8
not general, which means that neither all monosubsti-
tuted compounds are active, nor all disubstituted are
inactive, for example, compound 3 appeared to taste
sweet. More recently we have also found that the
replacement of the carboxylic function by amide or
tetrazole moiety resulted in the loss of sweet activity;
however, the compounds are active bitter tastants.16
Discovering drugs is a complicated issue that lacks gen-
eral approach. Basically, an efficient technology together
with a precise knowledge of the real or possible ligand–
receptor interactions should make drug discovery a dead
certainly. However, it is not a fact and the analysis of the
SAR by screening receptor ligands is still an important
design strategy even in these cases when we have 3D
receptor data. Paradoxically, so called fragment ap-
proach that insists on the importance of the certain
two-dimensional molecular frameworks for the drug-
likeness and lead generation has just appeared.9 There-
fore, we followed similar strategy in our study.
As a first attempt we designed 1-cycloalkanecarboxylic
acids 4 whose cycle was conceived as the result of super-
imposition of the active parent or acyclic structures hav-
ing 2-methyl substituent (Chart 2). Our hypothesis that
the inclusion of such a group would afford compounds
retaining sweet taste was supported by molecular mode-
ling investigations. This shows that in fact two alkyl sub-
stituent can favor similar conformational profiles for
active compounds, which has also been proved by the
X-ray structures and 3D QSAR analysis.17 The only ac-
tive cyclic structure found among ASA compounds is a
parent compound 1. By removing 2-dimethyl substitu-
ents in the parent structure 1 or 4, 5 or 6-member ana-
logs we obtained nonsweet compounds.1 These data
suggest that the methyl substitution at the C2 atom is
of the key importance for the activity of phenyl-
sulfonylcycloalkanecarboxylic analogs 4. We speculated
also that the hydrophobic interactions of the 2-methyl
group could explain the activity. At the same time a
question comes how important is the distance between
carboxylic function and sulfonyl group. Therefore, we
also obtained a series of 2-arylsulfonylalkanecarboxylic
acids (3-arylsulfonylbutanoic acids) 5 to test the affect
of the extension of the distance between the carboxyl
and arylsulfonyl functions on the compound activity.
Formally, a chain of these compounds also contains 2-
methyl group.
Chart 2 illustrates the basic structure–taste-regularities
in the series of arylsulfonylalkanoic acids (ASA) ob-
tained and tested in previous studies. Thus, besides par-
ent compound 110, most of the active analogs are found
among acyclic forms 2 and 3 that are mostly Ca-alkyl-
monosubstituted acids 2.1,10–15 However, this rule is
CO2H
SO2
CO2H
SO2
CO2H
SO2
1
2
3
SO2
X
CO2H
SO2
3. Chemistry
CO2H
Cyclohexane analogs 4 were obtained by the Diels–Al-
der cycloaddition as shown in Scheme 1. We used the
reaction similar to those of the Paquette for the cycliza-
tion of phenyl vinyl sulfone and butadiene.18 This gave
unsaturated cyclohexene sulfones 6. Carboxylation of
4
5
Chart 2. Design of arylsulfonyl(cyclo)alkanecarboxylic acids 4 and 5.
R1
R1
SO2Ph
R1
R
SO2Ph
R2
SO2Ph
R
2
i
+
2
ii
COOH
4
R3
R
R
R
4
R
R3
4
3
6
7
iii
R1
SO2Ph
COOH
R2
R3
R4
4
Scheme 1. Reagents and conditions: (i) method A: benzene, hydroquinone, 120–135ꢁC (22–28h), method B: xylene, 30min; (ii) n-BuLi, CO2, H+/
H2O; (iii) CH3OH, H2, Pt/C.

V. Lysiak et al. / Bioorg. Med. Chem. 13 (2005) 671–675
673
R
R
i
COOH
COOH
X
SH
+
S
X
COOH
ii
R
O
S
X
O
5
Scheme 2. Reagents and conditions: (i) Et3N, THF, 0ꢁC; (ii) CH3COOH, 30% H2O2.
cyclohexene sulfones by the treatment of n-BuLi and
CO2 gave 1-phenylsulfonylcyclohexenecarboxylic acids
7, respectively, and the hydrogenation of 7 with hydro-
gen provides a variety of 1-phenylsulfonylcyklohexane-
carboxylic acids 4 of the different methyl-substitution
pattern. 2-Arylsulfonylalkanecarboxylic acids 5 were
prepared in the reaction of thiophenols with the, a,b-
unsaturated acids in Et3N/THF similarly to the previ-
ously reported synthesis of Yoonmo and Cohen.19 The
resulted 2-phenyltioalkanecarboxylic acids were oxi-
dized by 30% H2O2 in acetic acid (Scheme 2).
sweet tastant–receptor interactions. The rich methyl
substitution pattern within cyclohexane ring generated
a bulky molecule, in contrary, double bond molecule
that is much more flat evoked sweet taste. In turn,
almost all 2-phenylsulfonylalkanecarboxylic (3-phenyl-
sulfonylalkanoic) acids appeared to be inactive and bit-
ter. Acid 5e is the only exclusion, as this compound has
been reported to have sweet and bitter taste. Interest-
ingly, also this molecule includes two methyl groups,
that is b-methyl and aromatic methyl substituent.
The inactivity of the Cl-arylog 5b clearly implies
4. Results and discussion
Table 1. Taste of acids 4, 5, 7
R1
R1
2,4-Dimethyl-1-phenylsulfonylcyklohexanecarboxylic
acid 4f appeared to be the only active compound among
compounds 4. This means that a double methyl substitu-
tion is needed in the cyclohexane ring to elicit sweet taste
of compounds 4. Quite surprisingly, a majority of the
synthetic precursors of 4, that is, 2-methyl-1-cyklohe-
xenecarboxylic acids 7 are potent sweet tastants, includ-
ing single 2-methyl group substituted analog 7c.
Moreover pure sweet taste was observed for active com-
pounds 4 and 7. Sweet taste threshold concentrations
range from 0.750 to 0.500mmol/L (Table 1). This com-
pares advantageously to the recognition threshold
values of sucrose (10–12mmol/L) or cyclamate (1–
3mmol/L), but is higher than the respective values for
saccharin (0.015–0.030mmol/L), acesulfame K (0.070–
X
R1
SO2Ph
COOH
SO2Ph
COOH
R2
R2
R
COOH
X
SO2
R4
R3
R4
3 X
4
5
7
Compound R1
R2
R3
H
R4
X
Taste/Csw
[mmol/L]a
4a
4b
4c
4d
4e
4f
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Br
Cl
H
Inactive
Inactive
Inactive
Inactive
Inactive
0.625b
CH3
H
H
CH3
CH3 CH3
CH3 CH3 CH3
CH3 CH3
H
5a
5b
5c
5d
5e
5f
CH3
CH3
CH3
H
—
—
—
—
—
—
H
—
—
—
—
—
—
H
—
—
—
—
—
—
H
Inactive
Bitter
Inactive
0.130mmol/L)20 or the parent compound
(0.250mmol/L).15
1
CH3 Bitter
CH3 0.750 Sweet-bitter
CH3
H
2,4-Dimethyl-unsaturated analog 7f appeared to be the
most active among all newly synthesized compounds.
Thus 2,4-dimethyl location seems to be optimal eliciting
sweetness both in cyclohexane 4 and cyclohexene 7 ser-
ies. An alternative introduction of the methyl groups in
position R3 and R4 does not deprive compound 7d of
their sweet taste activity; however, similar compound
4d is inactive. It is worth noticing that also a substitution
of three cyclohexene ring hydrogens with methyl groups
(compound 7e) generates an active molecule, while sim-
ilar cyclohexane analog 4e is inactive. These regularities
seems to indicate, that methyl group can interact with
the receptor as an important part of hydrophobic moi-
ety. We believe the inactivity of 4 in comparison to the
activity of 7 can be explained by steric hindrance during
H
Bitter
7a
7b
7c
7d
7e
7f
H
—
—
—
—
—
—
Inactive
0.750b
0.750b
0.750b
0.625b
0.500b
H
H
CH3
H
H
CH3
H
H
H
H
CH3 CH3
H
CH3 CH3 CH3
CH3 CH3
H
H
a Measured using the Belitz double blind test.20 The panel consisted of
four members. A person not participating in the tests encoded all
compounds. The recognition threshold values were estimated by
testing 1mL portion of the samples of decreasing concentration.
Each concentration was encoded with two samples of tap water. The
lowest concentration for which the judgments of the panelists are
correct is then averaged.
b Pure sweet taste without any aftertaste.

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V. Lysiak et al. / Bioorg. Med. Chem. 13 (2005) 671–675
hydrophobic interactions of the methyl group. This sug-
gests that the methyl groups form important hydropho-
bic binding sites for sweet taste glucophore in the
obtained series. Moreover, the inactivity of the majority
of compounds 5 indicates that sulfonyl and carboxylic
functions are fundamental pharmacophoric elements
that are of the crucial importance for the compound
sweetness.
6.1.6. 3-Phenylsulfonylpropionic acid (5f). (24% yield).
Mp = 123ꢁC, lit. mp = 124–125ꢁC.24
6.2. Phenylsulfonylcyclohex-3-enes 6
6.2.1. Method A. A mixture of phenyl vinyl sulfone or
phenyl-1-propenyl sulfone (0.0035molar equiv), dieno-
file (1,3-diene) (0.0033molar equiv), benzene (5mL),
and hydroquinone (15mg) was heated in an evacu-
ated Carius tube at 120–135ꢁC for 22–28h. The crude
isolated product was eluted through silica gel with
20% ethyl acetate in hexane. The recovered color-
less, crystalline solid was used without further
purification.
5. Conclusions
In summary a potent series of alternative sweeteners
have been identified. The analysis of the SAR regulari-
ties for the series indicates that the methyl substituents
in 1-(cyklo)alkanecarboxylic acids are of the key impor-
tance for the activity of the new compounds synthesized.
6.2.2. Method B. A mixture of sulfolene (0.017molar
equiv), phenyl vinyl sulfone or phenyl-1-propenyl sulf-
one (0.012molar equiv) and xylene (2mL) was shaken
in a closed flask. After 30min xylene was evaporated
and a crude product was crystallized from benzene.
6. Experimental
General procedure
6.2.3. 1-Phenylsulfonylcyclohex-3-ene (method B). (76%
yield). Mp = 74–76ꢁC, 1H NMR (CDCl3) d 1.9 (m,
2H), 2.3 (m, 2H), 3.7 (m, 1H), 5.4 (m, 1H), 5.9 (m,
1H), 7.5–7.9 (m, 5H). AE: calcd C, 64.84; H, 6.35;
found: C, 64.56; H, 6.82.
6.1. 3-Arylsulfonylalkanoic acids 5
The unsaturated acid (0.050molar equiv) was added
dropwise to a solution of thiophenol (0.051molar equiv)
and triethylamine (0.055molar equiv) in THF (7.5mL)
at 0ꢁC. After being stirred for 1h at 0ꢁC, the reaction
mixture was warmed to room temperature, stirred over-
night, quenched with 5% HCl (38mL), and extracted
with ether. The combined ether layer was washed with
brine, dried over MgSO4, and concentrated by rotary
evaporation to give the respective adducts.
6.2.4.
1-Phenylsulfonyl-3,4-dimethylcyclohex-3-ene
(method A). (76% yield). Mp = 79–81ꢁC, lit. mp =
79.5–81ꢁC.18
6.2.5. 1-Phenylsulfonyl-4-methylcyclohex-3-ene (method
A). (80% yield). Mp = 74ꢁC lit. mp = 79ꢁC.18
A 30% H2O2 (5mL) in CH3COOH (2.5mL) was added
with stirring to the obtained adduct (0.015molar equiv).
The reaction mixture was stirred overnight, heated at
60–80ꢁC for 4h, poured into water (15mL) and ex-
tracted with CH2Cl2. Organic phase was washed with
5% Na2S2O3, water, dried over MgSO4 and evaporated.
6.2.6. 1-Phenylsulfonyl-6-methylcyclohex-3-ene (method
B). (71% yield). Mp = 77–78ꢁC, H NMR (CDCl3) d
1.21–1.24 (d, 3H), 1.62–1.69 (m, 1H), 2.0–2.07 (m,
1H), 2.34–2.44 (m, 1H), 7.50–7.71 (m, 3H), 7.86–7.92
(m, 2H), 8.60 (s, 1H). MS 236 (M+H)+. AE: calcd C,
66.63; H, 7.99; found: C, 67.09; H, 7.64.
1
6.1.1. 3-(p-Bromophenylosulfonyl)butanoic acid (5a).
(25% yield). H NMR [(CD3)2CO] d 1.30 (d, 3H), 2.45
(q, 2H), 2.95 (q, 2H), 3.65 (m, 1H), 5.90 (s, –OH),
7.65–8.00 (m, Ar). IR (KBr) [cmÀ1] 3340–2905 (OH);
1694 (C@O); 1312 (SO2); 1136 (SO2). AE: calcd C,
39.10; H, 3.61; found: C, 39.09; H, 3.56.
6.2.7.
1-Phenylsulfonyl-3,4,6-trimethylcyclohex-3-ene
1
(method A). (74.9% yield). Mp = 81–82ꢁC, 1H NMR
(CDCl3) d 0.6 (d, 3H), 1.60 (d, 2 · 3H), 1.8 (d, 2H),
2.5 (m, 2H), 3.4 (m, 1H), 3.8 (m, 1H), 7.60–8.0 (m,
5H). MS 264 (M+H)+. AE: calcd C, 68.14; H, 7.62;
found: C, 67.98; H, 7.46.
6.1.2. 3-(p-Chlorophenylosulfonyl)butanoic acid (5b).
(11% yield). H NMR [(CD3)2CO] d 1.30 (d, 3H), 2.40
(q, 2H), 2.90 (q, 2H), 3.60 (m, 1H), 5.56 (s, –OH),
7.60–8.05 (m, Ar). IR (KBr) [cmÀ1] 3400–2906 (OH);
1693 (C@O); 1313 (SO2); 1137 (SO2). AE: calcd C,
45.72; H, 4.22; found: C, 45.73; H 4.24.
6.2.8.
1-Phenylsulfonyl-4,6-dimethylcyclohex-3-ene
1
(method A). (74.3% yield). Mp = 79–81ꢁC, 1H NMR
(CDCl3) d 0.6 (d, 3H), 1.63 (s, 3H), 1.8 (d, 2H), 2.0
(m, 2H), 3.4 (m, 2H), 5.8 (m, 1H), 7.6–8.0 (m, 5H).
MS 250 (M+H)+. AE: calcd C, 67.63; H, 8.32; found:
C, 67.31; H, 7.99.
6.1.3. 3-Phenylosulfonylbutanoic acid (5c). (52% yield).
Mp = 102ꢁC, lit. mp = 102.5–103.5ꢁC.21
6.3. Phenylsulfonylcyclohexenocarboxylic acids 7
A solution of sulfone (0.011molar equiv) in 80mL of
dry diethyl ether in an argon atmosphere protected from
external moisture was cooled externally to 5ꢁC. A
solution of butyllithium in hexane (15.5mL of 1.6M
solution) was added with stirring during 10min. The
mixture temperature rose during the addition. After
6.1.4. 3-(p-Tolilosulfonyl)propionic acid (5d). (38% yield).
Mp = 95ꢁC, lit. mp = 113–114ꢁC.22
6.1.5. 3-(p-Tolilosulfonyl)butanoic acid (5e). (69% yield).
Mp = 134ꢁC, lit. mp = 133.5–134ꢁC.23

V. Lysiak et al. / Bioorg. Med. Chem. 13 (2005) 671–675
675
the additional 10min of stirring with external ice bath
cooling, the milky-yellow reaction mixture was added
to about 100g of crushed solid carbon dioxide, stirred,
and then poured into a shallow dish open to air. Next
day the residue was dissolved in warm water, and ex-
tracted two times with benzene, 10% NaOH, acidified
with HCl, and extracted three times with methylene
chloride. The organic layer was dried over MgSO4,
and concentrated by evaporation.
6.4.2. 1-Phenylsulfonyl-4-methylcyclohexanecarboxylic
acid (4b). (80% yield). Mp = 89–90ꢁC 1H NMR (CDCl3)
d 0.9 (d, 3H), 1.6–2.8 (m, 6H), 7.6–8.2 (m, 5H).
6.4.3. 1-Phenylsulfonyl-2-methylcyclohexanecarboxylic
acid (4c). (90% yield). Mp = 112–114ꢁC 1H NMR
(CDCl3) d 1.2 (d, 3H), 1.3–2.8 (m, 9H), 7.6–8.2 (m, 5H).
6.4.4. 1-Phenylsulfonyl-2,4-dimethylcyclohexanecarboxy-
lic acid (4d). (86% yield) Mp = 99–101ꢁC 1H NMR
(CDCl3) d 0.9 (d, 3H), 1.3 (d, 3H), 1.6–2.8 (m, 6H),
7.6–8.2 (m, 5H).
6.3.1. 1-Phenylsulfonyl-3-cyclohexenecarboxylic acid (7a)
1
(method B). (54.4% yield). Mp = 171–177ꢁC, H NMR
(CDCl3) d 2.1–3.2 (3 · m, 6H), 5.8 (m, 1H), 6.1 (m,
1H), 7.6–8.2 (m, 5H). MS 267 (M+ H)+. AE: calcd C,
58.63; H, 5.30; found: C, 58.86; H, 5.46.
6.4.5. 1-Phenylsulfonyl-2,4,5-trimethylcyclohexanecarb-
oxylic acid (4e). (90% yield). Mp = 123–125ꢁC 1H
NMR (CDCl3) d 0.9 (d, 2 · 3H), 1.2 (d, 3H), 1.6–2.8
(m, 6H), 7.6–8.2 (m, 5H).
6.3.2. 1-Phenylsulfonyl-4-methyl-3-cyclohexenecarboxy-
1
lic acid (7b). (57% yield). Mp = 182–184ꢁC, H NMR
(CDCl3) d 1.6 (s 3H), 2.0–3.3 (m, 6H), 5.6 (m, 1H),
7.6–8.0 (m, 5H). MS 281 (M+ H)+. AE: calcd C, 59.98;
H, 5.75; found: C, 60.16; H, 5.62.
6.4.6. 1-Phenylsulfonyl-3,4-dimethylcyclohexanecarboxy-
lic acid (4f). (80% yield). Mp = 67–71ꢁC 1H NMR
(CDCl3) d 0.9 (m, 2 · 3H), 1.4 (m, 2 · 1H), 2.3–2.9 (m,
6H), 7.6–8.2 (m, 5H).
6.3.3. 1-Phenylsulfonyl-6-methyl-3-cyclohexenecarboxy-
lic acid (7c) (method B). (53.9% yield). Mp = 197–
199ꢁC 1H NMR (CDCl3) d 1.6 (d, 2 · 3H), 2.1–3.2
(m, 6H), 7.6–8.0 (m, 5H). MS 281 (M+H)+. AE: calcd
C, 59.98; H, 5.75; found: C, 59.64; H, 5.49.
References and notes
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1227.
6.3.6. 1-Phenylsulfonyl-3,4-dimethyl-3-cyclohexenecarb-
oxylic acid (7f). (54% yield). Mp = 221–223ꢁC 1H
NMR (CDCl3) d 1.6 (d, 2 · 3H), 2.1–3.2 (m, 6H), 7.6–
8.0 (m, 5H). MS 295 (M+H)+. AE: calcd C, 61.20; H,
6.16; found: C, 61.16; H, 6.17.
6.4. Phenylsulfonylcyclohexanecarboxylic acids 4
Hydrogen was inserted to a mixture of 7.5mL dry meth-
anol and palladium 10% on charcoal (100mg) at room
temperature for 20min. After that time unsaturated acid
(0.5g) in 3mL dry methanol was injected through the
syringe and hydrogen was passed for the additional
10–30min. The catalyst was removed by filtration, and
the solvent was evaporated. Crude product was crystal-
lized from pentane.
17. Polanski, J.; Ratajczak, A.; Gasteiger, J.; Gałdecki, Z.;
Gałdecka, E. J. Mol. Struct. 1997, 40, 71.
18. Carr, R. V. C.; Williams, R. V.; Paquette, L. A. J. Org.
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19. Yoonmo, A.; Cohen, T. J. Org. Chem. 1994, 59(11), 3142.
20. Gries, H.; Mutzel, W.; Belitz, H.; Wiese, H.; Krase, I.;
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22. Bonet, P.; Najera, C. J. Org. Chem. 1994, 59(11), 3202.
23. Achmatowicz, O.; Michalski, J. Rocz. Chem. 1956, 30,
243.
6.4.1. 1-Phenylsulfonylcyclohexanecarboxylic acid (4a).
(80% yield). Mp = 156ꢁC, lit. mp = 156–158ꢁC.11
24. Hogeveen, H.; Montanari, F. J. Chem. Soc. 1963, 4864.