Acid-catalysed reactions of activated benzofuranylmethanols: Formation of calixbenzofurans

Article abstract of DOI:10.1016/S0040-4020(02)00472-6

Regiochemistry of electrophilic substitution of the 3-substituted-4,6-dimethoxybenzofurans is largely controlled by the substituents at C3. The presence of a 3-aryl group results in the preferred formation of 2-substituted benzofuran derivatives whereas a bulky tert-butyl 3-substituent leads to a dominance of 7-substituted products. Acid-catalysed reactions of 2-hydroxymethylbenzofurans give mainly unsymmetrically linked calix[3]benzofurans. However, acid treatment of 7-hydroxymethylbenzofurans affords only the symmetrically linked calix[3]benzofurans in high yields. Benzofuranyl glyoxylamides, glyoxylates and ketones can be obtained in high yields and the acid-catalysed reactions of their corresponding alcohol reduction products generally give moderate to high yields of the symmetrically linked calix[3]benzofurans together with a minor amount of a calix[4]benzofuran.

Full text of DOI:10.1016/S0040-4020(02)00472-6

TETRAHEDRON
Pergamon
Tetrahedron 58 @2002) 5125±5134
Acid-catalysed reactions of activated benzofuranylmethanols:
formation of calixbenzofurans
David StC. Black,p Donald C. Craig, Naresh Kumar and Robert Rezaie
School of Chemical Sciences, The University of New South Wales, UNSW, Sydney, NSW 2052, Australia
Dedicated to Professor Lutz Tietze on the occasion of his 60th birthday
Received 8 January 2002; revised 28 March 2002; accepted 25 April 2002
AbstractÐRegiochemistry of electrophilic substitution of the 3-substituted-4,6-dimethoxybenzofurans is largely controlled by the sub-
stituents at C3. The presence of a 3-aryl group results in the preferred formation of 2-substituted benzofuran derivatives whereas a bulky tert-
butyl 3-substituent leads to a dominance of 7-substituted products. Acid-catalysed reactions of 2-hydroxymethylbenzofurans give mainly
unsymmetrically linked calix[3]benzofurans. However, acid treatment of 7-hydroxymethylbenzofurans affords only the symmetrically
linked calix[3]benzofurans in high yields. Benzofuranyl glyoxylamides, glyoxylates and ketones can be obtained in high yields and the
acid-catalysed reactions of their corresponding alcohol reduction products generally give moderate to high yields of the symmetrically linked
calix[3]benzofurans together with a minor amount of a calix[4]benzofuran. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
benzofuranylmethanols were then obtained by a simple
reduction process.
We have previously shown that calix[3]benzofurans could
be obtained from the reactions of activated benzofurans with
aldehydes.1 In general, these trimeric macrocycles are
formed predominantly with an unsymmetrical [2,2;7,2;7,7]
linkage pattern. We now report that some activated benzo-
furanylmethanols undergo acid-catalysed cyclo-oligomeri-
sation to give a range of calix[3]- and [4]benzofurans.
Similar reactions on analogous indoles have also been
reported by our research group.2
The Vilsmeier formylation of the 3-phenylbenzofuran 1a
with N,N-dimethylformamide and phosphoryl chloride at
0±258C gave only the 2-carbaldehyde derivative 2a in
90% yield, since C2 of the activated benzofurans is gener-
ally more reactive than C7. When the temperature of the
reaction mixture was raised to 508C, the 7-carbaldehyde
isomer 3a was obtained in 11% yield together with a 76%
yield of the 2-carbaldehyde 2a. However, when the 3-tert-
butylbenzofuran 1b was formylated under the same con-
ditions, the major product was the 7-carbaldehyde 3b,
formed in 68% yield together with 31% of the 2-isomer
2b, because of the steric hindrance effect of the 3-tert-
butyl group. Reactions of the benzofuran 1a with
N,N-dimethylarylamides or N,N-dimethylacetamide in the
presence of phosphoryl chloride at 908C gave similarly
only the 2-substituted derivatives 4a±c in yields of
45±71% @Scheme 1).
2. Results and discussion
A series of activated benzofuranylmethanols was thus
prepared via regioselective electrophilic substitution
reactions. 3-Substituted-4,6-dimethoxybenzofurans were
formylated using phosphoryl chloride and N,N-dimethyl-
formamide, as previously described on related indoles,3±6
and this was followed by a reduction step to afford hydroxy-
methylbenzofuran derivatives. Benzofuran ketone deriva-
We have previously reported that 3-aryl-4,6-dimethoxy-
indoles undergo reaction with oxalyl chloride to give a
mixture of 2- and 7-glyoxyloyl chloride derivatives.9 In
contrast, the reaction of oxalyl chloride with 4,6-di-
methoxy-3-phenylbenzofuran 1a resulted in the formation
of only the 2-substituted glyoxyloyl chloride, which reacted
readily with amines and methanol to give the corresponding
glyoxylic amides 5a±c and ester 5d in 82±99% yield
@Scheme 2).
tives were prepared by
a
similar method7,8 using
phosphoryl chloride and appropriate N,N-dimethylamides.
3-Substituted-4,6-dimethoxybenzofurans were also acyl-
ated with oxalyl chloride and were subsequently converted
to glyoxylic amide and ester derivatives by the previously
reported method utilised to prepare analogous indoles.6 The
Keywords: calixarenes; benzofurans; oligomerisation; macrocycles.
Corresponding author. Tel.: 161-2-9385-4657; fax: 161-2-9385-6141;
e-mail: d.black@unsw.edu.au
p
Reduction of activated benzofuran aldehydes and ketones to
the corresponding benzofuranylmethanols 6, 7 and 10 was
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020@02)00472-6

5126
D.StC.Black et al./ Tetrahedron 58 %2002) 5125±5134
Scheme 1.
Scheme 2.
Scheme 3.

D.StC.Black et al./ Tetrahedron 58 %2002) 5125±5134
5127
Scheme 4.
carried out with sodium borohydride at room temperature
or diisobutylaluminium hydride at 2768C. Treatment of
2-hydroxymethylbenzofurans 6a, b with Montmorillonite
clay in dichloromethane gave the unsymmetrically linked
calix[3]benzofurans 9a, b, respectively, as major products
whereas the acid-catalysed reactions of 7-hydroxymethyl-
benzofurans 7a, b afforded only the symmetrically linked
calix[3]benzofurans 8a, b in high yields @Scheme 3).
Figure 1. X-Ray crystal structure of compound 11d(i).

5128
D.StC.Black et al./ Tetrahedron 58 %2002) 5125±5134
Molecular mechanics calculations indicate that the sym-
metrically linked calix[3]benzofuran 8 is less stable than
the unsymmetrically linked isomer 9, consistent with
compound 8 being the kinetic product and compound 9
the thermodynamic product. Reactions of the 7-methanols
7 are faster than those of the 2-methanols 6, because C2 is
more nucleophilic than C7. It is interesting that the 3-t-butyl
group does not impede reaction of the benzylic alcohol at C2.
University and Mrs Berta Litvak at the University of New
1
South Wales. H and 13C NMR spectra were obtained in
deuterated chloroform on a Bruker CXP 300 @300 MH)
spectrometer. Infrared spectra were recorded on an ATI
Mattson Genesis Series FTIR spectrometer using KBr
discs. The e.i. mass spectra were recorded on a VG Quatro
mass spectrometer at 70 eV ionising potential with an ion
source temperature of 2108C. MALDI spectra were obtained
on a DESTR VOYAGER. Flash chromatography was
carried out using Merck silica gel 230±400 mesh Kieselgel
60, whilst analytical thin-layer chromatography was
performed on 0.2 mm plates precoated with silica gel 60
F254. For the structure determination of compound 11d(i),
re¯ection data were measured with an Enraf±Nonius
CAD-4 diffractometer in u/2u scan mode using graphite
In contrast to the 2-substituted benzofuran primary alcohols,
the acid-catalysed reactions of secondary alcohol deriva-
tives 10a±g gave only the symmetrically oriented calix-
benzofurans 11a±g in 26±85% yields. Incorporation of
the 4-chlorophenyl substituent led to the formation of the
calix[4]benzofuran 12 in 19% yield as well as the major
component @75%) of calix[3]benzofuran 11b @Scheme 4).
Compound 12 is the ®rst example of a calix[4]hetarene with
substitution at the linking carbon atom.
Ê
monochromatized copper radiation @l 1.54184 A). Data
were corrected for absorption using the analytical method
of de Meulenaer and Tompa.11 Re¯ections with I . 3sꢀI†
were considered observed. The structure was determined by
direct phasing and Fourier methods. Re¯ection weights used
were 1=s2ꢀF0†; with sꢀF0† being derived from sꢀI0† ˆ
‰s2ꢀI0† 1 ꢀ0:04I0†2Š1=2: The weighted residual is de®ned as
Compound 11a has previously been prepared by the acid-
catalysed reaction of benzofuran 1a with 4-tolualdehyde,
and also characterised by its X-ray crystal structure.1
Compound 11d was a mixture of two con®gurational
isomers and these were separated by ¯ash chromatography.
The crystal structure of one isomer 11d(i) @Fig. 1) shows the
product to exist in a symmetrically linked ¯attened partial
cone con®guration with the three tert-butylcarboxamido
groups oriented in one equatorial and two axial positions.
From the 1H NMR data, it appears that this compound is in
equilibrium with a cone conformer in solution. The spec-
trum shows singlet resonances at d 1.11, 5.27, 5.60,
6.17 ppm designated to t-butyl, alkyl CH, amide NH and
benzofuran H5, respectively, and this pattern is consistent
P
P
Rw ˆ ꢀ wD2= wF02†1=2: Atomic scattering factors and
anomalous dispersion parameters were from International
Tables for X-ray Crystallography.12 Structure solution was
by SIR9213 and re®nement used RAELS.14 ORTEP-II15
running on a Power Macintosh was used for the structural
diagram, and a DEC Alpha-AXP workstation was used for
calculations.
4.1.1. 4,6-Dimethoxy-3-phenylbenzofuran-2-carbalde-
hyde (2a). @i) A solution of phosphoryl chloride @0.21 ml,
2.27 mmol) in N,N-dimethylformamide @3 ml) was allowed
to stir for 1 h. 4,6-Dimethoxy-3-phenylbenzofuran1 1a
@0.5 g, 1.97 mmol) was then added and the resulting mixture
was allowed to continue stirring overnight at room tempera-
ture. A solution of sodium hydroxide @10%) was then added
and the mixture was extracted with dichloromethane
@3£15 ml). The combined extracts were concentrated and
the remaining crude residue was chromatographed to
give 4,6-dimethoxy-3-phenylbenzofuran-2-carbaldehyde 2a
@0.50 g, 90%) as colourless crystals, mp 177±1798C @from
ethyl acetate/light petroleum). @Found: C, 72.1; H, 4.8.
1
with a cone structure.10 In the H NMR spectrum of the
¯attened partial cone isomers, each of these groups give
rise to three singlets and that is consistent with the data
obtained for the other isomer 11d(ii). A crystal structure
of this product could not be obtained, so the precise orien-
tation of the substituted glyoxylic amide groups is unclear.
3. Conclusions
1
C17H14O4 requires C, 72.3; H, 5.0%). H NMR spectrum:
Both 2- and 7-hydroxymethylbenzofurans have been shown
to undergo acid-catalysed trimerisation to form calix[3]-
benzofurans. The 2-methanols favour formation of the
unsymmetrically-oriented structural isomer, while the
7-methanols give only the symmetrically-oriented isomers.
This latter isomer appears to be the kinetic product, which
would be favoured by the higher nucleophilicity of C2 over
C7. However, when the 2-hydroxymethyl group is substi-
tuted, so that the alcohol is secondary, the symmetrically-
oriented isomer is preferred. Steric effects are probably
relevant here, because a symmetrically-oriented calix[4]-
benzofuran is isolated as a minor product in one case.
d 3.74, 3.89 @6H, 2s, OMe); 6.32 @1H, d, Jˆ2.0 Hz, H5);
6.69 @1H, d, Jˆ2.0 Hz, H7); 7.45±7.59 @5H, m, aryl); 9.53
@1H, s, CHO). 13C NMR spectrum: d 55.5, 55.9 @OMe);
87.9, 95.7 @C5, C7); 127.8, 128.8, 130.8 @5£aryl CH);
110.0, 129.6, 135.7, 147.3, 156.7, 158.1, 163.5 @aryl C);
178.7 @CO). Mass spectrum: m/z 282 @M, 90%), 267 @10).
IR @KBr) nmax 2847, 1669, 1618, 1319, 1239, 1153,
1111 cm21
.
@ii) The above experiment was carried out at 508C and the
crude residue obtained was chromatographed @ethyl acetate/
light petroleum, 15:85 and then 30:70) to give two fractions.
The ®rst fraction contained aldehyde 2a @470 mg, 76% from
560 mg of the starting material). The second fraction
contained 4,6-dimethoxy-3-phenylbenzofuran-7-carbalde-
hyde 3a @70 mg, 11%) as pale yellow crystals, mp 210±
2138C @from ethyl acetate/light petroleum). @Found: C,
71.8; H, 5.0. C17H14O4 requires C, 72.3; H, 5.0%). 1H
NMR spectrum: d 3.91, 4.00 @6H, 2s, OMe); 6.33 @1H, s,
4. Experimental
4.1. General
Melting points are uncorrected. Microanalyses were
performed by Ms Reet Bergman of the Australian National

D.StC.Black et al./ Tetrahedron 58 %2002) 5125±5134
5129
H5); 7.61 @1H, s, H2); 7.36±7.56 @5H, m, aryl); 10.48, s
@CHO). 13C NMR spectrum: d 55.6, 56.6 @OMe); 89.7
@C5); 141.4 @C2); 127.3, 127.9, 129.3 @5£aryl CH); 106.2,
110.8, 122.1, 131.5, 141.4, 160.1, 163.2 @aryl C); 186.2
@CO). Mass spectrum: m/z 282 @M, 32%), 236 @5), 182
@40), 139 @100). IR @KBr) nmax 2954, 1674, 1600, 1339,
4.1.4.
2-(40-Chlorobenzoyl)-4,6-dimethoxy-3-phenyl-
benzofuran (4b). As described for the preparation of ketone
4a, benzofuran 1a @1.0 g, 3.94 mmol) was treated with
a mixture of N,N-dimethyl-4-chlorobenzamide @1.20 g,
6.54 mmol) and phosphoryl chloride @0.45 ml, 4.83 mmol)
to give a crude residue which was chromatographed to
give two fractions. The ®rst fraction contained the starting
material @0.19 g, 19%). The second fraction contained
2-%40-chlorobenzoyl)-4,6-dimethoxy-3-phenylbenzofuran 4b
@1.10 g, 71, 88% based on recovered starting material) as
yellow crystals, mp 74±768C @from ethyl acetate/light
petroleum). @Found: C, 70.3; H, 4.3. C23H17ClO4 requires
C, 70.3; H, 4.4%). 1H NMR spectrum: d 3.65, 3.85 @6H, 2s,
OMe); 6.30 @1H, d, Jˆ2.1 Hz, H5); 6.68 @1H, d, Jˆ2.1 Hz,
H7); 7.20±7.71 @1H, m, aryl). 13C NMR spectrum: d
55.2, 55.6 @OMe); 87.6, 95.3 @C5, C7); 126.9, 127.6,
127.9, 130.5, 130.7 @9£aryl CH); 111.4, 131.3, 135.8,
138.0, 145.8, 156.2, 156.9, 162.3 @aryl C); 183.2 @CO).
Mass spectrum: m/z 394 @M 37Cl, 33%), 392 @M 35Cl,
100%), 139 @100). IR @KBr) nmax 2444,1643, 1542, 1506,
1229, 1111, 1069 @CO) cm21
.
4.1.2. 3-t-Butyl-4,6-dimethoxybenzofuran-2-carbalde-
hyde (2b) and 3-t-butyl-4,6-dimethoxybenzofuran-7-
carbaldehyde (3b). As described for benzofuran 1a,
4,6-dimethoxy-3-t-butylbenzofuran1 1b @770 mg, 6.40)
was treated with a mixture of phosphoryl chloride @0.6 ml,
6.45 mmol) and N,N-dimethylformamide @4 ml) to give a
crude residue which was chromatographed @ethyl acetate/
light petroleum, 30:70) to give two fractions. The ®rst
fraction contained 3-t-butyl-4,6-dimethoxybenzofuran-2-
carbaldehyde 2b @270 mg, 31%) as colourless crystals, mp
111±1138C @from ethyl acetate/light petroleum). @Found: C,
68.5; H, 7.2. C15H18O4 requires C, 68.7; H, 6.9%). 1H NMR
spectrum: d 1.60 @9H, s, CMe3); 3.84, 3.94 @6H, 2s, OMe);
6.32 @1H, d, Jˆ2.0 Hz, H5); 6.64 @1H, d, Jˆ2.0 Hz, H7);
10.22 @1H, s, CHO). 13C NMR spectrum: d 31.6 @CMe3);
33.9 @CMe3); 55.1, 55.4 @OMe); 87.6, 95.2 @C5, C7); 111.5,
143.1, 146.9, 155.3, 158.0, 162.2 @aryl C); 180.6 @CO). IR
1285, 1528, 1111 cm21
.
4.1.5. 2-Acetyl-4,6-dimethoxy-3-phenylbenzofuran (4c).
As described for the preparation of ketone 4a, benzofuran
1a @250 mg, 0.98 mmol) was reacted with a mixture of
N,N-dimethylacetamide @0.15 ml, 1,57 mmol) and phos-
phoryl chloride @0.11 ml, 1.18 mmol) to give 2-acetyl-4,6-
dimethoxy-3-phenylbenzofuran 4c @160 mg, 55%) as pale
brown crystals, 198±2008C @from ethyl acetate/light petro-
leum). @Found: C, 72.8, H, 5.5. C18H16O4 requires C, 73.0;
H, 5.5%). 1H NMR spectrum: d 2.23 @3H, s, Me); 3.61, 3.85
@6H, 2s, OMe); 6.25 @1H, d, Jˆ2.1 Hz, H5); 6.66 @1H, d,
Jˆ2.1 Hz, H7); 7.39±7.46 @5H, m, aryl). 13C NMR
spectrum: d 28.0 @3H, s, Me); 55.3, 55.6 @OMe); 87.6,
95.2 @C5, C7); 127.4, 128.0, 130.0 @5£aryl CH); 112.2,
129.1, 132.0, 146.5, 156.4, 156.5, 162.3 @aryl C); 188.0
@CO). Mass spectrum: m/z 296 @M, 100%), 295 @80), 281
@58), 225 @38). IR @KBr) nmax 2457, 1675, 1620, 1557, 1314,
@KBr) nmax 2956, 1651, 1622, 1578, 1205, 1153, 1121 cm21
Mass spectrum: m/z 262 @M, 90%), 247 @100).
.
The second fraction contained 3-t-butyl-4,6-dimethoxy-
benzofuran-7-carbaldehyde 3b @590 mg, 68%) as colourless
crystals, mp 162±1648C @from ethyl acetate/light petro-
leum). @Found: C, 68.8; H, 7.1. C15H18O4 requires C, 68.7;
1
H, 6.9%). H NMR spectrum: d 1.37 @9H, s, CMe3); 3.98,
4.05 @6H, 2s, OMe); 6.31 @1H, s, H5); 7.30 @1H, s, H2);
10.44 @1H, s, CHO). 13C NMR spectrum: d 30.0 @CMe3);
30.4 @CMe3); 55.3, 56.4 @OMe); 89.2 @C5); 139.0 @C2);
105.8, 111.6, 130.3, 156.9, 159.0, 162.5 @aryl C); 186.1
@CO). Mass spectrum: m/z 262 @M, 60%), 247 @100). IR
@KBr) nmax 2948, 1669, 1610, 1385, 1211, 1175, 1118 cm21
.
1221, 1157, 1107 cm21
.
4.1.3.
4,6-Dimethoxy-2-(40-methylbenzoyl)-3-phenyl-
4.1.6.
N-t-Butyl-2-(40,60-dimethoxy-30-phenylbenzo-
benzofuran (4a). A mixture of N,N-dimethyl-4-methyl-
benzamide @1.03 g, 6.32 mmol) and phosphoryl chloride
@0.45 ml, 4.83 mmol) was heated at 608C for 30 min. Benzo-
furan 1a @1.0 g, 3.94 mmol) was then added and the result-
ing mixture was heated at 908C overnight. A solution of
sodium hydroxide @10%) was then added and the solution
was extracted with dichloromethane @3£15 ml). The com-
bined extracts were dried, evaporated and chromatographed
to give 4,6-dimethoxy-2-%40-methylbenzoyl)-3-phenylbenzo-
furan 4a @660 mg, 45%) as a yellow gum which solidi®ed on
standing, mp 103±1058C @from ethyl acetate/light petro-
leum). @Found: C, 75.3; H, 5.2. C24H20O4.0.5H2O requires
C, 75.6; H, 5.5%). 1H NMR spectrum: d 2.34 @3H, s, MePh);
3.70, 3.88 @6H, 2s, OMe); 6.32 @1H, d, Jˆ2.0 Hz, H5); 6.71
@1H, d, Jˆ2.0 Hz, H7); 7.08, 7.69 @4H, 2d, Jˆ8.2 Hz;
MePh); 7.07±7.42 @5H, m, aryl). 13C NMR spectrum: d
21.5 @Me); 55.4, 55.8 @OMe); 87.8, 95.3, @C5, C7); 127.1,
127.5, 128.5, 129.7, 130.7 @9£aryl CH); 111.7, 130.0, 131.7,
135.0, 142.7, 146.5, 156.3, 156.9, 162.1 @aryl C); 184.7
@CO). Mass spectrum: m/z 372 @M, 52%), 225 @5), 152
@12), 119 @60), 91 @100). IR @KBr) nmax 2458, 1637, 1506,
furan-20-yl)glyoxylamide (5a). To a solution of benzofuran
1a @1.0 g, 3.94) in dichloromethane @40 ml) was added
oxalyl chloride @0.4 ml, 4.53 mmol) and the resulting
solution was stirred overnight at 458C. An excess of tert-
butylamine was then added and the solution was allowed to
continue to stir for a further 1 h. The solvent was then
evaporated and the remaining residue was chromatographed
@ethyl acetate/light petroleum, 30:70) to give N-t-butyl-2-
%40,60-dimethoxy-30-phenylbenzofuran-20-yl)glyoxylamide
5a @1.40 g, 93%) as pale yellow crystals, mp 146±1478C
@from ethyl acetate/light petroleum). @Found: C, 69.5;
H, 6.4; N, 3.8. C22H23NO5 requires C, 69.3; H, 6.1;
N, 3.7%). 1H NMR spectrum: d 1.30 @9H, s, CMe3);
3.66, 3.87 @6H, 2s, OMe); 6.27 @1H, d, Jˆ2.2 Hz, H50);
6.74 @1H, d, Jˆ2.2 Hz, H70); 6.58 @1H, s, NH); 7.38±
7.44 @5H, m, aryl). 13C NMR spectrum: d 28.2 @CMe3);
51.5 @CMe3); 55.4, 55.8 @OMe); 87.9, 95.6 @C50, C70);
127.3, 128.1, 130.1 @5£aryl CH); 112.0, 131.7, 134.6,
144.6, 156.6, 158.1, 161.0 @aryl C); 163.2, 179.2 @CO).
Mass spectrum: m/z 381 @M, 5%), 281 @100), 254 @100),
225 @100). IR @Nujol) nmax 3254, 1671, 1640, 1451,
1278, 1153, 1111 cm21
.
1375, 1194 cm21
.

5130
D.StC.Black et al./ Tetrahedron 58 %2002) 5125±5134
4.1.7.
2-(40,60-Dimethoxy-30-phenylbenzofuran-20-yl)-
@Found: C, 71.5; H, 5.9. C17H16O4 requires C, 71.8; H,
5.7%). H NMR spectrum: d 3.72, 3.86 @6H, 2s, OMe);
1
glyoxylamide (5b). As described for the preparation of
glyoxylamide 5a, benzofuran 1a @500 mg, 1.97 mmol) was
reacted with oxalyl chloride and then quenched with an
excess of ammonia to give 2-%40,60-dimethoxy-30-phenyl-
benzofuran-20-yl)glyoxylamide 5b @711 mg, 90%) as pale
yellow crystals, mp 186±1878C @from ethyl acetate/light
petroleum). @Found: C, 66.3; H, 4.8; N, 4.3. C18H15NO5
4.67, @2H, s, CH2OH); 6.33 @1H, d, 2.6 Hz, H50); @1H,
d, Jˆ2.6 Hz, H7); 7.37±7.52 @5H, m, aryl). 13C NMR
spectrum: d 55.4, 55.8 @OMe); 56.2 @CH2OH); 88.2, 94.6
@C5, C7); 127.2, 127.7, 130.4 @5£aryl CH); 111.1, 119.9,
132.2, 150.0, 154.9, 156.4, 159.4 @aryl C). Mass spectrum:
m/z 284 @M, 100%), 267 @80). IR @KBr) nmax 3379, 2956,
1
requires C, 66.5; H, 4.7; N, 4.3%). H NMR spectrum: d
1621, 1501, 1211, 1146, 1114 cm21
.
3.67, 3.88 @6H, 2s, OMe); 5.57 @1H, s, NH); 6.27 @1H, d,
Jˆ2.0 Hz, H50) 6.71 @1H, d, Jˆ2.0 Hz, H70); 6.57 @1H, s,
NH); 7.38±7.50 @5H, m, aryl). 13C NMR spectrum: d 55.4,
55.8 @OMe); 87.8, 95.7 @C50, C70); 127.2, 128.4, 130.2
@5£aryl CH); 112.0, 131.2, 134.9, 144.2, 156.6, 158.2,
163.5 @aryl C); 164.3, 178.1 @CO). Mass spectrum: m/z
325 @M, 6%), 313 @12), 281 @50), 225 @10). IR @KBr) nmax
4.1.11. 7-Hydroxymethyl-4,6-dimethoxy-3-phenylbenzo-
furan (7a). As described for the preparation of alcohol 6a,
treatment of aldehyde 3a @100 mg, 0.355 mmol) with an
excess of sodium borohydride gave 7-hydroxymethyl-4,6-
dimethoxy-3-phenylbenzofuran 7a @98%) as a colourless
solid, mp 138±1408C @from dichloromethane). @Found: C,
71.2; H, 6.1. C17H16O4 requires C 71.8; H, 5.7%). 1H NMR
spectrum: d 3.84, 3.96 @6H, 2s, OMe); 4.29, sbr, OH); 4.98
@2H, d, Jˆ5.1 Hz, CH2OH); 6.42 @1H, s, H5); 7.52 @1H, s,
H2); 7.33±7.62 @5H, m, aryl). 13C NMR spectrum: d 54.9
@CH2OH); 55.6, 56.6 @OMe); 90.9 @C5); 127.1, 127.9, 129.2
@5£aryl CH); 140.3 @C2); 106.4, 120.0, 120.1, 122.9, 130.9,
132.2, 154.2 @aryl C). Mass spectrum: m/z 284 @M, 100%),
267 @90), 252 @50), 237 @60). IR @KBr) nmax 3462, 2937,
3449, 3196, 1704, 1648, 1617, 1306, 1534, 1220 cm21
.
4.1.8. N-Methyl-2-(40,60-dimethoxy-30-phenylbenzofuran-
20-yl)glyoxylamide (5c). As described for the preparation of
glyoxylamide 5a, benzofuran 1a @500 mg, 1.97 mmol) was
treated with oxalyl chloride and then quenched with excess
of methylamine @20% aqueous solution) to give N-methyl-2-
%40,60-dimethoxy-30-phenylbenzofuran-20-yl)glyoxylamide 5c
@550 mg, 82%) as pale yellow crystals, mp 176±1788C @from
ethyl acetate/light petroleum). @Found: C, 67.2; H, 4.9; N,
4.1. C19H17NO5 requires C, 67.3; H, 5.1; N, 4.1%). 1H NMR
spectrum: d 2.76 @3H, d, Jˆ5.1 Hz, NMe); 3.68, 3.88 @6H,
2s, OMe); 6.27 @1H, d, Jˆ2.0 Hz, H50); 6.72 @2d, Jˆ2.0 Hz,
H70); 6.56 @1H, br s, CONH); 7.39±7.48 @5H, m, aryl). 13C
NMR spectrum: d 25.8 @NMe); 55.3, 55.7 @OMe); 87.8, 95.6
@C50, C70); 127.1, 128.3, 130.1 @5£aryl CH); 111.9, 131.2,
134.6, 144.3, 156.6, 158.1, 163.2 @aryl C); 163.3, 179.0 @CO).
Mass spectrum: m/z 339 @M, 40%), 281 @100), 266 @7), 225
@35). IR @Nujol) nmax 3303, 1670, 1647, 1624, 1458, 1368,
1628, 1513, 1333, 1122, 1088 cm21
.
4.1.12. 3-t-Butyl-7-hydroxymethyl-4,6-dimethoxybenzo-
furan (7b). As described for the preparation of alcohol
6a, treatment of aldehyde 3b @410 mg, 1.55 mmol) with
an excess of sodium borohydride gave 3-t-butyl-7-hydroxy-
methyl-4,6-dimethoxybenzofuran 7b @405 mg, 98%) as a
colourless solid, mp 110±1118C @from ethyl acetate/light
petroleum). @Found: C, 68.0; H, 7.9. C15H20O4 requires C,
1
68.2; H, 7.6%). H NMR spectrum: d 1.39 @9H, s, CMe3);
3.93, 3.96 @6H, 2s, OMe); 4.91 @2H, s, CH2OH); 6.37 @1H, s,
H5); 7.19 @1H, s, H2). 13C NMR spectrum: d 30.1 @CMe3);
30.6 @CMe3); 54.7 @CH2OH); 55.1, 56.6 @OMe); 90.2 @C5);
137.9 @C2); 105.9, 110.8, 131.2, 153.1, 156.0, 156.5 @aryl
C). Mass spectrum: m/z 264 @M, 100%), 249 @80). IR @KBr)
1299 cm21
.
4.1.9. Methyl 2-(40,60-dimethoxy-30-phenylbenzofuran-
20-yl)glyoxylate (5d). As described for the preparation of
glyoxylamide 5a, benzofuran 1a @1.0 g, 3.94 mmol) was
reacted with oxalyl chloride @0.4 ml, 4.53 mmol) and then
quenched with methanol to give methyl 2-%40,60-dimethoxy-
30-phenylbenzofuran-20-yl)glyoxylate 5d @1.32 g, 99%) as
pale yellow crystals, mp 157±1588C. @Found: C, 66.7; H,
nmax 3494, 2956, 1627, 1516, 1205, 1120, 1094 cm21
.
4.1.13.
a-(4-Chlorophenyl)-4,6-dimethoxy-3-phenyl-
benzofuran-2-methanol (10b). As described for the prepa-
ration of alcohol 6a, treatment of ketone 4b @870 mg,
2.22 mmol) with an excess of sodium borohydride gave
a-%4-chlorophenyl)-4,6-dimethoxy-3-phenylbenzofuran-2-
methanol 10b @0.86 g, 99%) as a colourless gum which
solidi®ed on standing, mp 64±668C @methanol). @Found:
C, 69.7; H, 4.9. C23H19ClO4 requires C, 70.0; H, 4.9%).
1H NMR spectrum: d 2.62 @1H, s, OH); 3.70, 3.82 @6H,
2s, OMe); 5.83 @1H, s, alkyl CH); 6.32 @1H, d, 2.0 Hz);
6.62 @1H, d, Jˆ2.0 Hz, H70); 7.29±7.50 @5H, m, aryl). 13C
NMR spectrum: d 55.4, 55.7 @OMe); 67.4 @alkyl CH); 88.3,
94.7 @C5, C7); 127.4, 127.8, 127.9, 128.5, 130.3 @9£aryl
CH); 110.9, 119.8, 132.0, 133.5, 139.6, 149.9, 154.8,
156.3, 159.5 @aryl C). Mass spectrum: m/z 396 @M 37Cl,
31%), 394 @M 35Cl, 90%), 379 @40), 377 @100), 363 @38),
139 @100). IR @KBr) nmax 3417, 2960, 1616, 1505, 1217,
1
4.8. C19H16O6 requires C, 67.1; H, 4.7%). H NMR spec-
trum: d 3.36 @3H, s, COOMe); 3.67, 3.89 @6H, 2s, ArOMe);
6.28 @1H, d, Jˆ2.0 Hz, H50); 6.68 @1H, d, Jˆ2.0 Hz, H70);
7.48 @5H, m, aryl). 13C NMR spectrum: d 52.1 @COOMe);
55.3, 55.7 @ArOMe); 87.6, 95.6 @C50, C70); 127.3, 128.6,
130.2 @5£aryl CH); 111.7, 134.8, 143.6, 157.0, 158.1,
163.6 @aryl C); 163.8, 175.6 @CO). Mass spectrum: m/z
340 @M, 20), 281 @100), 267 @15), 225 @20). IR @KBr) nmax
3097, 1749, 1662, 1625, 1549, 1505, 1229 cm21
.
4.1.10. 2-Hydroxymethyl-4,6-dimethoxy-3-phenylbenzo-
furan (6a). To a stirred solution of aldehyde 2a @140 mg,
0.496 mmol) in methanol @10 ml) was added an excess of
sodium borohydride. After 1 h water was added and the
solution was concentrated in vacuo and extracted with
dichloromethane @3£10 ml). The combined extracts were
dried and evaporated to give 2-hydroxymethyl-4,6-
dimethoxy-3-phenylbenzofuran 6a @139 mg, 99%) as a
colourless solid, mp 135±1368C @from ethyl acetate).
1153, 1111 cm21
.
4.1.14.
N-t-Butyl-2-(40,60-dimethoxy-30-phenylbenzo-
furan-20-yl)-2-hydroxyethanamide (10d). As described
for the preparation of alcohol 6a, reaction of glyoxylamide

D.StC.Black et al./ Tetrahedron 58 %2002) 5125±5134
5131
5a @1.40 g, 3.67 mmol) with an excess of sodium boro-
hydride gave N-t-butyl-2-%40,60-dimethoxy-30-phenylbenzo-
furan-20-yl)-2-hydroxyethanamide 10d @1.39 g, 99%) as
colourless crystals, mp 85±888C @from ethyl acetate/light
petroleum). @Found: C, 68.2; H, 6.8; N, 3.6. C22H25NO5
oxaheptacyclo[17.5.2.23,9.211,17.05,29.013,27.021,25]triaconta-
1%24),3,5%29),6,8,11,13%27),14,16,19,21%25),22-dodecaene
8a @16 mg, 19%) as colourless crystals, mp 278±2818C
@from ethyl acetate/light petroleum) @lit.,1 278±2818C).
The second fraction contained 6,8,14,16,20,22-hexa-
methoxy-4,12,24-triphenyl-25,28,30-trioxaheptacyclo-
[17.5.2.23,9.211,17.05,29.013,27.023,26]triaconta-1%24),3,5%29),6,
8,11,13%27),14,16,19,21,23%26)-dodecaene 9a @62 mg,
74%) as colourless crystals, mp 185±1878C @from ethyl
acetate/light petroleum) @lit.1 185±1878C).
1
requires C, 68.9; H, 6.6; N, 3.7). H NMR spectrum: d
1.31 @9H, s, CMe3); 3.70, 3.84 @6H, 2s, OMe); 5.03 @1H,
s, CHOH); 5.30 @1H, s, CHOH); 5.84 @1H, br, CONH); 6.32
@1H, d, Jˆ2.0 Hz H50); 6.65 @1H, d, Jˆ2.0 Hz, H70); 7.36±
7.62 @5H, m, aryl). 13C NMR spectrum: d 28.3 @CMe3); 51.1
@CMe3); 55.1, 55.4 @OMe); 66.2 @alkyl CH); 88.1, 94.4 @C50,
C70); 127.1, 127.4, 130.3 @5£aryl CH); 110.7, 121.1, 131.5,
147.8, 154.5, 156.0, 159.2 @aryl C); 168.8 @CO). Mass
spectrum: m/z 383 @M, 5%), 283 @100), 267 @10). IR @KBr)
4.1.18. Reaction of alcohol 7a with K10 clay to give calix-
benzofuran (8a). As described for alcohol 6a, alcohol 7a
@100 mg, 0.352 mmol) was treated with K10 clay to give
calix[3]benzofuran 8a1 @71 mg, 76%).
n
max 3371, 3215, 1737, 1656,1528, 1215, 1153, 1111 cm21
.
4.1.15. 2-(40,60-Dimethoxy-30-phenylbenzofuran-20-yl)-2-
hydroxyethanamide (10e). As described for the prepara-
tion of alcohol 6a, treatment of glyoxylamide 5b @460 mg,
1.425 mmol) with an excess of sodium borohydride gave
2-%40,60-dimethoxy-30-phenylbenzofuran-20-yl)-2-hydroxy-
ethanamide 10e @457 mg, 98%) as colourless crystals, mp
88±908C @from ethyl acetate/light petroleum). @Found: C,
66.2; H, 5.5; N, 4.1. C18H17NO5 requires C, 66.1; H, 5.2; N,
4.1.19. Reaction of alcohol 7b with K10 clay to give calix-
benzofuran (8b). As described for alcohol 6a, alcohol 7b
@220 mg, 0.833 mmol) was treated with K10 clay to give
4,12,20-tri-t-butyl-6,8,14,16,22,24-hexamethoxy-26,28,30-
trioxaheptacyclo[17.5.2.23,9.211,17.05,29.013,27.021,25]triaconta-
1%24),3,5%29),6,8,11,13%27),14,16,19,21%25),22-dodecaene
8b @199 mg, 97%) as colourless crystals, mp 273±2758C
@lit.1 273±2758C).
1
4.3%). H NMR spectrum: d 2.60 @1H, sbr, CHOH); 3.71,
3.83 @6H, 2s, OMe); 5.17 @1H, s, CHOH); 5.74, 6.07 @2H,
2s, CONH2); 6.31 @1H, d, Jˆ2.0 Hz, H50); 6.64 @1H,
d, Jˆ2.0 Hz, H70); 7.37±7.60 @5H, m, aryl). 13C NMR
spectrum: d 55.4, 55.8 @OMe); 66.0 @CHOH); 88.3, 94.9
@C50, C70); 127.6, 127.9, 130.4 @5£aryl CH); 110.7, 131.4,
133.1, 146.8, 154.9, 156.4, 159.9 @aryl C); 172.1 @CO). Mass
spectrum: m/z 327 @M, 10%), 283 @90), 267 @15). IR @KBr)
4.1.20. Reduction of aldehyde 2b with sodium boro-
hydride and reaction of the resulting alcohol 6b with
K10 clay to give calixbenzofurans (8b and 9b). Benzo-
furan 2b @300 mg, 1.15 mmol) was reduced with sodium
borohydride as described for the preparation of alcohol
6a. The resulting alcohol 6b was treated directly with K10
clay in dichloromethane. After stirring overnight, the solu-
tion was ®ltered through Celite. The ®ltrate was evaporated
and chromatographed @ethyl acetate/light petroleum, 7:93
and then 10:90) to give two fractions. The ®rst fraction
contained calix[3]benzofuran 8b @50 mg, 18% for two
steps). The second fraction was 4,12,24-tri-t-butyl-
6,8,14,16,20,22-hexamethoxy-25,28,30-trioxaheptacyclo-
[17.5.2.23,9.211,17.05,29.013,27.023,26]triaconta-1%24),3,5%29),6,
8,11,13%27),14,16,19,21,23 %26)-dodecaene 9b @90 mg,
32% for two steps) as colourless crystals, mp 174±1778C
@from ethyl acetate/light petroleum) @lit.1 174±1778C).
n
max 3445, 3147, 1699, 1606, 1507, 1222, 1146, 1111 cm21
.
4.1.16.
N-Methyl-2-(40,60-dimethoxy-30-phenylbenzo-
furan-20-yl)-2-hydroxyethanamide (10f). As described
for the preparation of alcohol 6a, treatment of glyoxylamide
5c @475 mg, 1.401 mmol) with an excess of sodium boro-
hydride gave N-methyl-2-%40,60-dimethoxy-30-phenylbenzo-
furan-20-yl)-2-hydroxyethanamide 10f @473 mg, 99%) as
colourless crystals, mp 100±1038C @from ethyl acetate/
light petroleum). @Found: C, 66.4; H, 5.9; N, 3.8.
1
C19H19NO5 requires C, 66.8; H, 5.6; N, 4.1%). H NMR
spectrum: d 1.05 @1H, sbr, CHOH); 2.84 @3H, d, Jˆ5.1 Hz,
NMe); 3.70, 3.83 @6H, 2s, OMe); 5.30 @1H, s, CHOH); 6.14
@1H, d, Jˆ5.1 Hz, NH); 6.31 @1H, d, Jˆ2.0, H50); 6.64 @1H,
d, Jˆ2.0, H70); 7.36±7.61 @5H, m, aryl). 13C NMR spec-
trum: d 26.3 @NMe); 55.4, 56.0 @OMe); 66.2 @CHOH); 88.3,
94.8 @C50, C70); 127.5, 127.8, 130.5 @5£aryl CH); 110.8,
122.0, 131.5, 147.2, 145.8, 156.3, 159.7 @aryl C); 170.4
@CO). Mass spectrum: m/z 341 @M, 1%), 327 @5), 280
@60), 249 @30), 207 @30), 180 @100), 165 @100). IR @KBr)
nmax 3396, 3228, 1662, 1538, 1507, 1222, 1153, 1111
4.1.21. Reduction of ketone 4a and reaction of the result-
ing alcohol 10a with K10 clay to give calixbenzofuran
(11a). As described for the preparation of alcohol 6a, ketone
4a @315 mg, 0.85 mmol) was reduced with sodium boro-
hydride to give alcohol 10a @312 mg, 99%). This alcohol
@260 mg, 0.7 mmol) was treated with K10 clay as described
for the synthesis of calix[3]benzofuran 8a to give 6,8,
14,16,22,24-hexamethoxy-2,10,18-tri%40-methylphenyl)-4,12,
20-triphenyl-26,28,30-trioxaheptacyclo[17.5.2.23,9.211,17
.05,29.013,27.021,25]-triaconta-1%24),3,5%29),6,8,11,13%27),14,
16,19,21%25),22-dodecaene 11a @210 mg, 85%) as colour-
less crystals, mp 190±1928C @from ethyl acetate/light
petroleum) @lit.1 190±1928C).
@CO) cm21
.
4.1.17. Reaction of alcohol 6a with K10 clay to give calix-
benzofurans (8a and 9a). To a solution of alcohol 6a
@90 mg, 0.317 mmol) in dichloromethane @20 ml) was
added K10 clay and the mixture was allowed to stir over-
night, then ®ltered through Celite. The ®ltrate was evapo-
rated and chromatographed @ethyl acetate/light petroleum,
25:75) to give two fractions. The ®rst fraction contained
6,8,14,16,22,24-hexamethoxy-4,12,20-triphenyl-26,28,30-tri-
4.1.22. Reaction of alcohol 10b with K10 clay to give
calixbenzofurans (11b and 12). As described for the
preparation of calix[3]benzofuran 8a, alcohol 10b @590
mg, 1.496 mmol) was treated with K10 clay to give a
crude residue which was chromatographed @ethyl acetate/
light petroleum, 15:85 and then 30:70) to afford two

5132
D.StC.Black et al./ Tetrahedron 58 %2002) 5125±5134
fractions. The ®rst fraction contained 2,10,18-tri%40-chloro-
phenyl)-6,8,14,16,22,24-hexamethoxy-4,12,20-triphenyl-26,
28,30-trioxaheptacyclo[17.5.2.23,9.211,17.05,29.013,27.021,25]-
triaconta-1%24),3,5%29),6,8,11,13%27),14,16,19,21%25),22-
dodecaene 11b @420 mg, 75%) as colourless crystals, mp
204±2078C @ethyl acetate/light petroleum). @Found: C,
@6£OMe); 90.6, 91.5, 92.0 @benzofuran C5); 125.9, 126.1,
126.4, 127.0, 127.1, 127.6, 130.1, 130.3, 130.7 @15£aryl
CH); 107.4, 108.1, 111.7, 113.1, 113.3, 114.0, 114.6,
115.0, 130.9, 133.6, 134.4, 134.5, 152.1, 152.2, 152.5,
153.2, 153.4, 153.5, 153.7, 153.8, 154.7, 154.9, 155.2,
155.9 @aryl C). Mass spectrum: m/z 841 @M11). IR @KBr)
1
73.2; H, 4.6. C69H51Cl3O9 requires C, 73.3; H, 4.6%). H
nmax 2932, 2335, 1615, 1506, 1329, 1205, 1153 cm21
.
NMR spectrum: d 3.54, 3.64, 3.74, 3.75, 3.84, 4.00 @18H,
6s, OMe); 5.97, 6.10, 6.18 @3H, 3s, alkyl CH); 6.21, 6.34,
6.50 @3H, 3s, benzofuran H5); 6.57±7.51 @27, m, aryl). 13C
NMR spectrum: d 37.1, 38.8, 38.9 @alkyl CH); 55.2, 55.4,
55.6, 56.0, 56.8, 57.1 @OMe); 90.5, 91.0, 91.4 @benzofuran
C5); 126.6, 127.0, 127.1, 127.2, 127.4, 128.1, 128.7, 129.8,
129.9, 130.0, 130.4, 131.2, 133.2 @27£aryl CH); 105.9,
106.5, 109.7, 111.8, 113.0, 113.5, 115.1, 115.7, 117.9,
125.8, 126.0, 130.5, 132.1, 132.9, 138.6, 139.0, 139.7,
151.0, 151.7, 152.5, 153.0, 153.1, 153.9, 154.5 @aryl C).
IR @KBr) nmax 2932, 2835, 1609, 1489, 1327, 1208, 1142,
1100 cm21. Mass spectrum: m/z @MALDI) 1129 @M11,
35Cl, 35Cl, 35Cl).
4.1.24. Reaction of alcohol 10d with p-toluenesulfonic
acid to give calixbenzofurans (11d). To a stirred solution
of alcohol 10d @610 mg, 1.59 mmol) in dichloromethane
@100 ml) was added p-toluenesulfonic acid and the mixture
was stirred for 5 days. The solvent was evaporated and the
crude residue was chromatographed @ethyl acetate/light
petroleum, 50:50) to give two fractions. The ®rst fraction
contained tri-t-butyl 6,8,14,16,22,24-hexamethoxy-4,12,20-
triphenyl-26,28,30-trioxaheptacyclo[17.5.2.23,9.211,17.05,29
.013,27.021,25]triaconta-1%24),3,5%29),6,8,11,13%27),14,16,19,
21%25),22-dodecaene-2,10,18-tricarboxamide 11d(i) @65 mg,
12%) as a colourless solid, mp 201±2038C @from ethyl
acetate/light petroleum). @Found: C, 71.2; H, 6.1; N, 3.6.
1
The second fraction contained 2,10,18,26-tetra-%40-chloro-
phenyl)-6,8,14,16,22,24,30,32-octamethoxy-4,12,20,28-
tetraphenyl-33,35,37,39-tetraoxanonacyclo[25.5.2.23,9
.211,17.219,25.05,34.013,36.021,38.029,40]tetraconta-1%40),3,5,7,
9%34),11,13,15,17%36),19,21,23,25%38),27,29,31-hexadeca-
ene 12 @105 mg, 19%) as colourless crystals after evapo-
ration, mp.3308C @ethyl acetate/light petroleum). @Found:
C, 73.1; H, 4.5. C92H68Cl4O12 requires C, 73.3; H, 4.6%). 1H
NMR spectrum: d 3.01, 3.15, 3.31, 3.49, 3.51, 3.52, 3.62,
3.92 @24H, 8s, OMe); 5.52, 5.84, 5.89, 5.98 @4H, 4s, alkyl
CH); 6.07, 6.12, 6.33 @4H, 3s, 4£H50); 6.45±7.60 @32H, m,
aryl). 13C NMR spectrum: d 36.8, 38.7, 39.8, 40.8 @alkyl
CH); 54.9, 55.4, 55.6, 55.7, 55.8, 56.2, 56.5, 57.3 @OMe);
91.3, 91.6, 92.5 @4£benzofuran C5); 125.2, 126.9, 127.2,
127.4, 127.8, 128.1, 129.3, 129.6, 130.1, 130.2, 130.3,
131.1 @36£aryl CH); 105.5, 105.6, 106.6, 106.7, 110.0,
112.3, 114.2, 114.9, 117.1, 117.7, 118.7, 118.9, 124.6,
125.0, 126.4, 126.5, 128.5, 130.0, 131.3, 131.5, 132.1,
132.6, 133.3, 133.9, 134.0, 139.5, 140.1, 140.3, 140.6,
148.3, 149.0, 150.6, 151.3, 152.9, 153.0, 153.1, 153.2,
153.4, 153.5, 154.0 @aryl C). Mass spectrum: m/z
@MALDI) 1505 @M11, 35Cl, 35Cl, 35Cl, 35Cl). IR @KBr)
C66H69N3O12´H2O requires C, 71.1; H, 6.4; N, 3.8%). H
NMR spectrum: d 1.11 @27H, s, 3£CMe3); 3.58, 3.64
@18H, 2s, 6£OMe); 5.27 @3H, s, 3£CH); 5.60 @3H, s, 3£
CONH); 6.17 @3H, s, 3£benzofuran H5); 7.20±7.50 @15H,
m, aryl). 13C NMR spectrum: d 28.5 @3£CMe3); 42.2
@3£alkyl CH); 51.1 @3£CMe3); 56.3, 56.8 @6£OMe); 91.7
@3£benzofuran C5); 126.8, 127.4, 130.2 @15£aryl CH);
102.8, 110.6, 117.9, 132.5, 147.2, 152.5, 154.3, 155.6
@24£aryl C); 167.9 @3£CO). Mass spectrum: m/z 1096
@M11, 100%), 731 @50). IR @KBr) nmax 3420, 2958, 1687,
1612, 1513, 1222, 1111 cm21
.
Crystal data for CCDC 178458.16 C69H75N3O13, M 1154.4,
monoclinic, space group P21/c, a 28.070 @13), b 22.912 @4),
Ê
Ê 3
c 21.396 @9) A, b 107.44 @2)8, V 13128 @8) A , Dc
1.17 g cm23, Z 8, mCu 6.19 cm21. Crystal size 0.19£
0.22£0.27 mm3, 2umax 908, min. and max.transmission
factors 0.87 and 0.90. The number of re¯ections was 6485
considered observed out of 10,585 unique data, with Rmerge
0.022 for 203 pairs of equivalent 0kl re¯ections. Final
residuals R, Rw were 0.088, 0.134 for the observed data.
The structure was described as a combination of four
types of re®neable identical groups @benzofuran, phenyl,
t-butyl, and acetone) and single atoms. The benzofuran,
phenyl and acetone groups were maintained planar, and
the t-butyl groups had three-fold symmetry. Thermal motion
was described by TLX rigid body thermal parameters, one
for the macrocycle, and one for each phenyl and t-butyl-
amide and acetone. Hydrogen atoms were included in
positions calculated each cycle, and their thermal motions
were assigned to the appropriate group.
nmax 2932, 2835, 1610, 1489, 1211, 1141, 1093 cm21
.
4.1.23. Reduction of ketone 4c and reaction of the result-
ing alcohol 10c with K10 clay to give calixbenzofuran
(11c). Ketone 4c @110 mg, 0.37 mmol) was reduced with
sodium borohydride using the usual procedure. This
resulting alcohol 10c was treated with K10 clay as described
for the preparation of calix[3]benzofuran 8a to give
6,8,14,16,22,24-hexamethoxy-2,10,18-trimethyl-4,12,20-tri-
phenyl-26,28,30-trioxaheptacyclo[17.5.2.23,9.211,17.05,29
.013,27.021,25]triaconta-1%24),3,5%29),6,8,11,13%27),14,16,19,
21%25), 22-dodecaene 11c @60 mg, 58% for two steps) as a
colourless solid, mp.3008C@from ethyl acetate/light petro-
leum). @Found: C, 77.3; H, 6.1. C54H48O9 requires C, 77.1;
The second fraction contained the isomer 11d(ii) @100 mg,
17%) as a colourless solid, mp 277±2798C @from ethyl
acetate/light petroleum). @Found: C, 72.2; H, 6.7; N, 3.6.
1
C66H69N3O12 requires C, 72.3; H, 6.3; N, 3.8%). H NMR
1
H, 5.8%). H NMR spectrum: d 1.16, 1.51, 1.56 @9H, 3d,
spectrum: d 0.88, 0.92, 0.95 @3s, @27H, 3s, 3£CMe3); 3.43,
3.60, 3.62, 3.68, 3.83 @18H, 5s, 6£OMe); 5.11, 5.22, 5.30
@3H, 3s, alkyl CH); 5.60, 5.72, 6.04 @3H, 3s, CONH); 6.04,
6.26, 6.31 @3H, 3s, benzofuran H5); 6.70±7.53 @15H, m,
aryl). 13C NMR spectrum: d 28.0, 28.2, 28.5 @CMe3);
41.2, 41.5, 44.7, @CMe3); 50.5, 50.7, 51.3 @alkyl CH);
Jˆ8.2 Hz, Me); 3.26, 3.59, 3.63, 3.71, 3.72, 3.89 @18H, 6s,
OMe); 4.70, 4.76, 5.31 @3H, 3q, Jˆ8.2 Hz, alkyl CH); 6.10,
6.24, 6.43 @3H, 3s, benzofuran H5); 7.07±7.63 @1H, m, aryl
CH). 13C NMR spectrum: d 16.6, 17.8, 18.9 @Me); 26.7,
28.0, 28.5 @alkyl CH); 55.6, 55.8, 55.9, 57.0, 57.8

D.StC.Black et al./ Tetrahedron 58 %2002) 5125±5134
5133
55.3, 55.4, 55.8, 56.3, 56.9 @6£OMe); 90.6, 91.8, 92.2,
@benzofuran C5); 126.2, 126.7, 127.1, 127.2, 127.4, 127.7,
129.9, 130.0, 130.6 @15£aryl CH); 102.5, 103.2, 104.5,
111.5, 112.2, 114.0, 117.6, 117.8, 119.4, 132.3, 133.0,
133.1, 148.6, 149.0, 150.1, 152.8, 153.6, 153.8, 153.9,
155.1, 155.5, 155.8, 156.5 @aryl C); 166.8, 167.3, 168.4
@CO). Mass spectrum: m/z 1096 @M11, 100%), 731 @10).
IR @KBr) nmax 3431, 2972, 1681, 1612, 1513, 1333, 1208,
@770 mg, 2.24 mmol) in dichloromethane, under an atmos-
phere of nitrogen and cooled at 2768C with an acetone/
liquid nitrogen bath, was added diisobutylaluminium
hydride @2.5 ml, 2.5 mmol). The solution was stirred at
2768C for 45 min, allowed to come to room temperature
and a 50:50 mixture of water/methanol was added dropwise.
The two layers were separated and the aqueous phase was
extracted with dichloromethane. The combined organic
extracts were dried, evaporated and chromatographed
@ethyl acetate/light petroleum) to give the crude alcohol10g
@545 mg, 71%) as a pale yellow gum. 1H NMR spectrum: d
3.45 @1H, d, Jˆ5.0 Hz, OH); 3.71 @3H, s, COOMe); 3.78,
3.85 @6H, 2s, ArOMe); 5.23 @1H, d, Jˆ5.0 Hz, CHOH); 6.32
@1H, d, 1.7 Hz, H50); 6.65 @1H, d, Jˆ1.7 Hz, H70); 7.36±
7.44 @5H, m, aryl). 13C NMR spectrum: d 53.3 @COOMe);
55.4, 55.8 @2£ArOMe); 65.3 @alkyl CH); 88.2, 94.8 @C50,
C70); 127.5, 127.7, 130.5 @5£aryl CH); 110.9, 121.6, 131.6,
146.5, 155.0, 156.3, 159.8 @aryl C); 172.2 @CO). Mass spec-
trum: m/z 342 @M, 20%), 312 @5), 283 @100), 267 @27).
1090 cm21
.
4.1.25. Reaction of alcohol 10e with p-toluenesulfonic
acid to give calixbenzofuran (11e). As described for the
preparation of calix[3]benzofuran 11d, alcohol 10e
@200 mg, 0.612) was treated with p-toluenesulfonic acid to
give 6,8,14,16,22,24-hexamethoxy-4,12,20-triphenyl-26,28,
30-trioxaheptacyclo[17.5.2.23,9.211,17.05,29.013,27.021,25]tria-
conta-1%24),3,5%29),6,8,11,13%27),14,16,19,21%25),22-dodeca-
ene-2,10,18-tricarboxamide 11e @85 mg, 45%) as
colourless solid, mp 275±2788C @from ethyl acetate/
a
light petroleum). @Found: C, 67.2; H, 5.0, N, 4.3.
C54H45N3O12´2H2O requires C, 67.3; H, 5.1, N, 4.4%). H
1
As described for the preparation of calix[3]benzofuran 11d,
the crude alcohol 10g @400 mg, 1.170 mmol) was treated
with p-toluenesulfonic acid to give trimethyl 6,8,14,
16,22,24-hexamethoxy-4,12,20-triphenyl-26,28,30-trioxa-
heptacyclo[17.5.2.23,9.211,17.05,29.013,27.021,25]triaconta-1%24),
3,5%29),6,8,11,13%27),14,16,19,21%25),22-dodecaene-2,10,
18-tricarboxylate 11g @50 mg, 26%) as colourless crystals,
mp 176±1788C @from ethyl acetate/light petroleum).
@Found: C, 69.8; H, 5.1. C57H48O15 requires C, 70.4; H,
NMR spectrum: d 3.32, 3.63, 3.67, 3.78, 3.80, 3.81 @18H,
6s, OMe); 5.33, 5.69, 5.72 @3H, 3s, CH); 5.82, 5.88, 6.50
@3H, 3 br s, CONH); 6.16, 6.35, 6.37 @3H, 3s, benzofuran
H5); 7.33±7.57 @15H, m, aryl). 13C NMR spectrum: d 39.1,
40.7, 43.2 @alkyl CH); 55.6, 56.1, 56.8, 56.9 @6£OMe); 91.0,
91.1, 91.4 @benzofuran C5); 127.0, 127.1, 127.2, 127.4,
127.6, 127.8, 130.1, 130.6 @15£aryl CH); 102.1, 102.6,
103.5, 111.2, 112.3, 112.6, 119.2, 119.3, 119.7, 131.9, 132.5,
132.6, 147.7, 148.4, 148.5, 153.4, 153.8, 153.9, 154.1, 154.9,
155.3, 155.8, 155.9 @aryl C); 171.9, 172.0, 172.6 @CO). Mass
spectrum: m/z 928 @M11, 90%). IR @KBr) nmax 3476, 3377,
1693, 1600, 1513, 1333, 1139, 1097 cm21.
1
5.0%). H NMR spectrum: d 3.05, 3.27, 3.59, 3.63, 3.65,
3.67, 3.75, 3.79 @27H, 8s, 9£OMe); 5.35, 5.76, 5.79 @3H, 3s,
CH); 6.12, 6.32, 6.38 @3H, 3s, benzofuran H5); 7.32±7.55
@15H, m, aryl). 13C NMR spectrum: d 37.5, 39.3, 41.7
@COOMe); 51.7, 52.3, 52.4 @alkyl CH); 55.5, 55.6, 55.9,
56.8, 57.4 @6£OMe); 90.3, 91.0, 91.4 @benzofuran C5);
126.6, 127.2, 127.3, 127.6, 130.1, 130.2, 130.7 @15£aryl
CH); 101.9, 103.6, 112.1, 112.6, 112.8, 117.9, 118.3,
118.9, 132.9, 133.5, 147.5, 147.7, 149.1, 153.4, 153.6,
153.8, 154.4, 155.0 @aryl C); 169.7, 170.3, 170.7 @CO).
Mass spectrum: m/z 973 @M11, 100%). IR @KBr) nmax
4.1.26. Reaction of alcohol 10f with p-toluenesulfonic
acid to give calixbenzofuran (11f). As described for the
preparation of calix[3]benzofuran 11d, alcohol 10f @400 mg,
1.173 mmol) was treated with p-toluenesulfonic acid to give
trimethyl 6,8,14,16,22,24-hexamethoxy-4,12,20-triphenyl-
26,28,30-trioxaheptacyclo[17.5.2.23,9.211,17.05,29.013,27.021,25]-
triaconta-1%24),3,5%29),6,8,11,13%27),14,16,19,21%25),22-
dodecaene-2,10,18-tricarboxamide 11f @120 mg, 32%) as
a colourless solid, mp 234±2368C @from ethyl acetate/light
petroleum). @Found: C, 68.5; H, 5.3; N, 3.8.
2954, 2836, 1749, 1612, 1513, 1333, 1150, 1097 cm21
.
Acknowledgements
1
C57H51N3O12´2H2O requires C, 68.1; H, 5.5; N, 4.2%). H
NMR spectrum: d 2.10, 2.36, 2.50 @9H, 3d, Jˆ4.1 Hz,
NHMe); 3.46, 3.60, 3.63, 3.69, 3.70, 3.92 @18H, 6s, OMe);
5.28, 5.57, 6.34 @3H, 3d, Jˆ4.1 Hz, NH); 5.51, 5.59, 5.99
@3H, 3s, CH); 6.18, 6.20, 6.40 @3s, benzofuran H5); 6.97±
7.56 @15H, m, aryl). 13C NMR spectrum: d 26.0, 26.3, 27.1
@NMe); 40.1, 41.8, 43.0 @alkyl CH); 55.5, 55.6, 55.8, 56.0,
56.5, 57.4 @OMe); 90.8, 91.0, 92.0 @benzofuran C5); 126.6,
127.0, 127.1, 127.2, 127.5, 129.8, 130.1, 130.3, 130.6
@15£aryl CH); 102.0, 102.5, 103.7, 111.7, 111.8, 112.8,
117.4, 118.1, 119.6, 132.0, 132.4, 133.2, 148.3, 148.7,
149.1, 153.2, 153.5, 153.6, 153.8, 154.2, 155.0, 155.4,
156.0 @aryl C); 169.1, 169.6, 170.7 @CO). Mass spectrum:
m/z 970 @M11, 100%), 648 @100), 486 @20). IR @KBr) nmax
Financial support from the Australian Research Council is
gratefully acknowledged.
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