Molecular Architecture. 2.1 Synthesis and Metal Complexation of Heptacyclic Terpyridyl Molecular Clefts

Article abstract of DOI:10.1021/jo9720041

Methods are described for the synthesis of a series of functionalized derivatives of 9-butyl-1,2,3,4,5,6,7,8-octahydroacridine (9), a building block for several types of highly preorganized host compounds. A key intermediate is 5-benzylidene-9-butyl-2,3,5,6,7,8-hexahydroacridin-4(1H)-one (23), which can also be used in the syntheses of torands and hydrogen-bonding hexagonal lattice receptors. A tridentate cleft (20), consisting of 2,2′;6′,2″-terpyridine imbedded in a heptacyclic framework, and a corresponding pentadentate diketone (6) were synthesized from 9 in five and seven steps, respectively. The picrate extraction method was used to estimate the solution stabilities of alkali metal complexes of heptacyclic terpyridyls 6 and 20, which was also compared with a flexible terpyridyl (37). Alkali metal complexes of both heptacyclic terpyridyls showed relatively high K_S values, but low size selectivity. Pentadentate host 6 binds Na⁺ and K⁺ more strongly than do most hexadentate crown ethers; flexible tridentate analogue 37 failed to extract alkali metal picrates into chloroform. The complexation abilities of 6 and 20 are attributed to enforced orientation of functional group dipoles toward the center of the molecular cleft. Sodium and potassium picrate complexes of pentadentate cleft 6 were synthesized (1:1 stoichiometry), and a 2:1 complex of calcium triflate (6₂·(Ca(CF₃SO₃)₂)was also prepared.

Full text of DOI:10.1021/jo9720041

2232
J . Org. Chem. 1998, 63, 2232-2243
Molecu la r Ar ch itectu r e. 2.1 Syn th esis a n d Meta l Com p lexa tion of
Hep ta cyclic Ter p yr id yl Molecu la r Clefts
Thomas W. Bell,* Peter J . Cragg, Albert Firestone, Albert D.-I. Kwok, J ia Liu,
Richard Ludwig, and Andrej Sodoma
Department of Chemistry, University of Nevada, Reno, Nevada 89557-0020 and Department of Chemistry,
State University of New York, Stony Brook, New York 11794-3400
Received October 31, 1997
Methods are described for the synthesis of a series of functionalized derivatives of 9-butyl-
1,2,3,4,5,6,7,8-octahydroacridine (9), a building block for several types of highly preorganized host
compounds. A key intermediate is 5-benzylidene-9-butyl-2,3,5,6,7,8-hexahydroacridin-4(1H)-one
(23), which can also be used in the syntheses of torands and hydrogen-bonding hexagonal lattice
receptors. A tridentate cleft (20), consisting of 2,2′;6′,2′′-terpyridine imbedded in a heptacyclic
framework, and a corresponding pentadentate diketone (6) were synthesized from 9 in five and
seven steps, respectively. The picrate extraction method was used to estimate the solution stabilities
of alkali metal complexes of heptacyclic terpyridyls 6 and 20, which was also compared with a
flexible terpyridyl (37). Alkali metal complexes of both heptacyclic terpyridyls showed relatively
high Ks values, but low size selectivity. Pentadentate host 6 binds Na+ and K+ more strongly than
do most hexadentate crown ethers; flexible tridentate analogue 37 failed to extract alkali metal
picrates into chloroform. The complexation abilities of 6 and 20 are attributed to enforced
orientation of functional group dipoles toward the center of the molecular cleft. Sodium and
potassium picrate complexes of pentadentate cleft 6 were synthesized (1:1 stoichiometry), and a
2:1 complex of calcium triflate (62‚Ca(CF3SO3)2) was also prepared.
The discovery of alkali metal complexation by crown
at the expense of rapid equilibration. Fast kinetics
needed for many analytical and preparative applications
of metal ligands can be achieved by decreasing the
number of macrocyclic rings. For example, podands and
lariat ethers may be considered open-chain analogues of
crown ethers and cryptands, respectively. This modifica-
tion enhances exchange rates but reduces the selectivities
of the hosts and stabilities of the alkali metal complexes.
Our studies have explored the unique combination of
rigidity and planarity in hosts for metal ions. We have
previously shown that an all-sp2 hybridized hexaaza-18-
crown-6 host forms strong complexes with alkali metal
salts.1,8 We have also introduced the torands7 (e.g., 5),
in which the macrocyclic perimeter is completely formed
by smaller, fused rings. The stabilities of alkali metal
complexes of torand 5 are comparable to those of crypta-
spherands, yet cation exchange between host molecules
is faster. Reported herein are the syntheses and some
complexation properties of heptacyclic terpyridyl molec-
ular clefts, represented by diketone 6 in Figure 1. These
ethers2 foreshadowed development of several other host
families,3 including podands, cryptands,4 lariat ethers,5
spherands,6 cryptahemispherands,6c and torands.7 The
examples shown in Figure 1 illustrate the general trend
toward ion encapsulation and ligand rigidity for cryptands,
spherands and cryptaspherands, compared with crown
ethers. These structural modifications generally produce
higher selectivity and stronger binding of alkali metals
* Corresponding author at University of Nevada.
(1) Part 1: Bell, T. W.; Guzzo, F.; Drew, M. G. B. J . Am. Chem.
Soc. 1991, 113, 3115-3122.
(2) (a) Pedersen, C. J . J . Am. Chem. Soc. 1967, 89, 2495-2496. (b)
Pedersen, C. J . Science (Washington, D.C.) 1988, 241, 536-540.
(3) For general reviews, see: (a) Patai, S.; Rappaport, Z., Eds. Crown
Ethers and Analogues; Wiley: New York, 1989. (b) Inoue, Y.; Gokel,
G. W., Eds. Cation Binding by Macrocycles; Marcel Dekker: New York,
1990. (c) Atwood, J . L.; Davies, J . E. D.; MacNicol, D. D., Eds. Inclusion
Compounds; Oxford University Press: Oxford, 1991. (d) Vo¨gtle, F.
Supramolecular Chemistry; Wiley: New York, 1991. (e) Gokel, G. W.
Crown Ethers and Cryptands; Royal Society of Chem.: Cambridge,
1991. (f) Cooper, S. R., Ed. Crown Compounds: Toward Future
Applications; VCH: New York, 1992. (g) Balzani, V.; deCola, L., Eds.,
Supramolecular Chemistry; Kluwer: Dordrecht, 1992. (h) Gokel, G.
W., Ed. Advances in Supramolecular Chemistry, J AI Press: Greenwich,
CT, 1993; V.3. (i) Bradshaw, J . S.; Krakowiak, K. E.; Izatt, R. M. Aza-
Crown Macrocycles; Wiley: New York, 1993. (j) Izatt, R. M.; Pawlak,
K.; Bradshaw, J . S.; Bruening, R. L. Chem. Rev. 1995, 95, 2529-2586.
(k) Parker, D., Ed. Macrocycle Synthesis; Oxford University Press:
Oxford, 1996.
(7) (a) Bell, T. W.; Firestone, A. J . Am. Chem. Soc. 1986, 108, 8109-
8111. (b) Bell, T. W.; Firestone, A.; Hu, L.-Y.; Guzzo, F. J . Inclusion
Phenom. 1987, 5, 149-152. (c) Bell, T. W.; Firestone, A.; Ludwig, R.
J . Chem. Soc., Chem. Commun. 1989, 1902-1904. (d) Bell, T. W.;
Firestone, A.; Liu, J .; Ludwig, R.; Rothenberger, S. D. In Inclusion
Phenomena and Molecular Recognition; Atwood, J . L., Ed.; Plenum:
New York, 1990; pp 49-56. (e) Bell, T. W.; Liu, J . Angew. Chem., Int.
Ed. Engl. 1990, 29, 923-925. (f) Bell, T. W.; Cragg, P. J .; Drew, M.
G. B.; Firestone, A.; Kwok, D.-I. A. Angew. Chem., Int. Ed. Engl. 1992,
31, 345-347. (g) Bell, T. W.; Cragg, P. J .; Drew, M. G. B.; Firestone,
A.; Kwok, D.-I. A. Angew. Chem., Int. Ed. Engl. 1992, 31, 348-350.
(h) Bell, T. W. in ref 3f, pp 305-318. (i) Bell, T. W.; Cragg, P. J .; Drew,
M. G. B.; Firestone, A.; Kwok, D.-I.; Liu, J .; Ludwig, R. T.; Papoulis,
A. T. Pure Appl. Chem. 1993, 65, 361-366. (j) Boguslavsky, L.; Bell,
T. W. Langmuir 1994, 10, 991-993. (k) Bell, T. W.; Tidswell, J . in ref
3k, pp 119-143.
(4) (a) Lehn, J .-M. Angew. Chem., Int. Ed. Engl. 1988, 27, 89-112.
(b) Lehn, J .-M. Angew. Chem., Int. Ed. Engl. 1990, 29, 1304-1319. (c)
Dietrich, B.; Viout, P.; Lehn, J .-M. Macrocyclic Chemistry; VCH: New
York, 1993.
(5) (a) Inoue, Y.; Gokel, G. W., Eds. Cation Binding by Macrocycles;
Marcel Dekker: New York, 1990; pp 253-361. (b) Atwood, J . L.;
Davies, J . E. D.; MacNicol, D. D., Eds. Inclusion Compounds; Oxford
University Press: Oxford, 1991; pp 283-324. (c) Gokel, G. W. Chem.
Soc. Rev. 1992, 39-47.
(6) (a) Cram, D. J . Angew. Chem., Int. Ed. Engl. 1986, 25, 1039-
1057. (b) Cram, D. J . Science (Washington, D. C.) 1988, 240, 760-
767. (c) Cram, D. J .; Ho, S. P. J . Am. Chem. Soc. 1986, 108, 2998-
3005.
(8) (a) Bell, T. W.; Guzzo, F. J . Am. Chem. Soc. 1984, 106, 6111-
6112. (b) Bell, T. W.; Guzzo, F. Ann. N. Y. Acad. Sci. 1986, 471, 291-
294.
S0022-3263(97)02004-5 CCC: $15.00 © 1998 American Chemical Society
Published on Web 03/13/1998

Heptacyclic Terpyridyl Molecular Clefts
J . Org. Chem., Vol. 63, No. 7, 1998 2233
Sch em e 1a
lipophilicity of the host compounds, enabling the evalu-
ation of complexation by liquid-liquid or solid-liquid
extraction. By later synthetic modification, side-chains
might also be useful for immobilization or conjugation
of hosts to solid supports, soluble polymers, or biomol-
ecules.
Several methods were investigated for preparation of
BuOHA (9, Scheme 1). Direct alkylation11 of OHA or
corresponding pyrylium salts12 proved less useful than
a two-step approach involving tricyclic keto alcohol 7.
This crystalline intermediate can be easily prepared in
500-g batches by condensation of pentanal with cyclo-
hexanone.13 The procedure is a modification of reported
methods for condensation of cyclohexanone with aromatic
and shorter-chain aliphatic aldehydes.14 The configura-
tion of keto alcohol 7 is tentatively assigned as shown in
Scheme 1 by comparison with the structure of the methyl
analogue, which was assigned by spectroscopic methods.15
Tricyclic keto alcohols related to 7 are known to
undergo reverse intramolecular aldol condensation under
acidic conditions, yielding 1,5-diketones.16 Acidic pyroly-
sis gave only dehydration product 8,17 which probably
corresponds in structure to the HCl-catalyzed dehydra-
tion product of the methyl analogue of 7.14a Heating with
base (NaOH or NaHCO3) caused decomposition of 7 to
cyclohexanone, 2-pentylidenecyclohexanone, and other
products. Tricyclic keto alcohols may be converted
directly to OHA derivatives by reaction with ammonium
acetate,16b,c apparently by condensation of the 1,5-dike-
tone formed in situ. Ammonium acetate in acetic acid is
a general method for synthesis of pyridines from 1,5-
diketones,16c,18 but the yield of this cyclization is limited
by disproportionation of the intermediate dihydro-
pyridine.13b,16c,18a,19 Reaction of hydroxylamine hydro-
chloride with 1,5-diketones13a,18b,20 avoids the dispropor-
F igu r e 1. Representative members of several classes of host
compounds: crown ether (1), cryptand (2), spherand (3),
cryptaspherand (4), torand (5) and heptacyclic terpyridyl cleft
(6).
preorganized podands constitute a family of host com-
pounds that form alkali metal complexes of comparable
strength to those of crown ethers. Also reported are the
syntheses of key intermediates used to prepare torands7
and hexagonal lattice hosts for hydrogen-bonded com-
plexation of organic guests.7d,9
Resu lts a n d Discu ssion
Syn th eses. The 9-butyl-1,2,3,4,5,6,7,8-octahydroacri-
dine (BuOHA) ring system was chosen as the building
block for assembly of polycyclic clefts and torands because
octahydroacridines can be functionalized selectively and
the n-butyl group was expected to produce a good balance
between solubility, crystallinity, and spectroscopic sim-
plicity. Thummel et al.10 have used unsubstituted
1,2,3,4,5,6,7,8-octahydroacridine (OHA) for synthesis of
“polyaza cavity-shaped” molecules of similar structure to
the hexagonal lattice clefts described here. We recog-
nized that introduction of an alkyl group would enhance
(11) (a) Schultz, A. G.; Flood, L.; Springer, J . P. J . Org. Chem. 1986,
51, 838-841.
(12) Kharchenko, V. G.; Yartseva, N. M.; Kozhevnikova, N. I. Zh.
Org. Khim. (Engl. Trans.) 1973, 9, 187-190.
(13) (a) Bell, T. W.; Firestone, A. J . Org. Chem. 1986, 51, 764-765.
(b) Bell, T. W.; Cho, Y.-M.; Firestone, A.; Healy, K.; Liu, J .; Ludwig,
R.; Rothenberger, S. D. Org. Synth. 1990, 69, 226-237. (c) Bell, T.
W.; Cho, Y.-M.; Firestone, A.; Healy, K.; Liu, J .; Ludwig, R.; Rothen-
berger, S. D. Organic Syntheses; Freeman, J . P., Ed.; Wiley: New York,
1993; Coll. Vol. VIII, pp 87-93.
(14) (a) Plesek, J .; Munk, P. Collect. Czech. Chem. Commun. 1957,
22, 1596-1602. (b) Tilichenko, M. N. Uch. Zap. Saratovsk. Gos. Univ.
1962, 75, 60-65; Chem. Abstr. 1964, 60, 419a.
(15) (a) Pitha, J . J . Org. Chem. 1970, 35, 2411-2412. (b) Cocker,
W.; Shannon, P. V. R. Chem. Ind. 1988, 339-340.
(16) (a) Tilichenko, M. N.; Kharchenko, V. G. J . Gen. Chem. USSR
1959, 29, 2334-2336. (b) Tilichenko, M. N.; Kharchenko, V. G. J . Gen.
Chem. USSR 1960, 30, 2264-2266. (c) Vysotskii, V. I.; Tilichenko,
M. N. Khim. Geterotsikl. Soedin. (Engl. Trans.) 1969, 5, 560-561.
(17) The double bond position was assigned as shown in 8 according
to the absence of an olefinic resonance in the 1H NMR spectrum.
(9) (a) Bell, T. W.; Liu, J . J . Am. Chem. Soc. 1988, 110, 3673-3674.
(b) Bell, T. W.; Santora, V. J . J . Am. Chem. Soc. 1992, 114, 8300-
8302. (c) van Straaten-Nijenhuis, W. F.; de J ong, F.; Reinhoudt, D.
N.; Thummel, R. P.; Bell, T. W.; Liu, J . J . Membrane Sci. 1993, 82,
277-283. (d) Beckles, D. L.; Maioriello, J .; Santora, V. J .; Bell, T. W.;
Chapoteau, E.; Czech, B. P.; Kumar, A. Tetrahedron 1995, 51, 363-
376. (e) Bell, T. W.; Hou, Z.; Luo, Y.; Drew, M. G. B.; Chapoteau, E.;
Czech, B. P.; Kumar, A. Science (Washington, D.C.) 1995, 269, 671-
674. (f) Bell, T. W.; Hou, Z.; Zimmerman, S. C.; Thiessen, P. A. Angew.
Chem., Int. Ed. Engl. 1995, 34, 2163-2165. (g) Bell, T. W.; Hou, Z.
Angew. Chem. Int. Ed. Engl. 1997, 36, 1536-1538.
(10) (a) Thummel, R. P. Tetrahedron 1991, 34, 6851-6886. (b)
Thummel, R. P. Synlett 1992, 1-12.

2234 J . Org. Chem., Vol. 63, No. 7, 1998
Bell et al.
Sch em e 2a
Sch em e 3a
tionation of dihydropyridines, but colored byproducts are
formed and both methods produce 9 from 7 in comparable
yield.13,19 The method of choice for preparation of BuOHA
(9) is reaction of 7 with NH4OAc and Cu(OAc)2 in acetic
acid.13b,19 Cu2+ apparently oxidizes the intermediate
dihydropyridine before disproportionation occurs. With
modification of the workup method13b this reaction gives
a 95% yield of 9 on a 200-g scale. An alternative two-
step synthesis of BuOHA (9) via 1,2,3,4,5,6,7,8-octahy-
droxanthen-9-one (10)21 was also investigated. An im-
proved preparation21b of 10 was employed (cf. Scheme 1).
Reaction of 10 with butyllithium followed by NH4OAc in
acetic acid gave 9 in 95% yield. This method produces 9
in comparable overall yield from commercially available
starting materials and may be useful for introducing
other substituents.
acetate intermediate to 12.13 Two methods were used to
prepare ketone 13 from alcohol 12: CrO3/H2SO4 in
aqueous acetic acid23 and Swern oxidation.24 The latter
method gave a somewhat cleaner product, but the CrO3
method is preferred for large scale oxidations. An
alternative approach to 13 based on the two-step syn-
thesis of 6,7-dihydroquinolin-8(1H)-one from 5,6,7,8-
tetrahydroquinoline25 was also evaluated. Condensation
of excess 9 with benzaldehyde gave a mixture of diben-
zylidene derivative 14 and the desired monobenzylidene
product (15)26 which was ozonized to ketone 13.
Coupling of two OHA subunits to form heptacyclic
terpyridyls, such as 6, requires oxidation of the methyl-
ene group adjacent to the pyridine N atom (position 4).
This was accomplished via N-oxide 11 (Scheme 2), which
can be prepared by reaction of 9 with MCPBA10a,13 or
Oxone (2KHSO5‚KHSO4‚K2SO4).13b Both oxidation reac-
tions give 11 in high yield, but the lower cost of Oxone
favors this method for large scale preparations. Buffer-
ing by NaHCO3 prevents the reaction mixture from
becoming acidic, reducing the reactivity of 9 by protona-
tion on nitrogen. A modification of the published
procedure13b is reported in the experimental section.
Functionalization of C4 was accomplished by Katada or
Boekelheide rearrangement22 of 11 and hydrolysis of the
Three approaches were used for symmetrical coupling
of two molecules of ketone 13 to form heptacyclic terpy-
ridyl 20 (Scheme 3). This transformation is precedented
by two syntheses of 5,6,8,9-tetrahydroquino[8,7-b]-
[1,10]phenanthroline from 6,7-dihydroquinolin-8(1H)-
one: reaction of the enamine with formaldehyde, followed
by cyclization of the intermediate 1,5-diketone with
NH4OAc;18d and condensation of the ketone with its
â-aminomethylene ketone derivative.27 The latter method
involving a â-heterosubstituted enone is attractive be-
cause it offers access to unsymmetrical terpyridyls from
two different ketones. Condensation of 13 with ethyl
formate gave â-hydroxymethylene ketone 16, which was
converted to â-ethoxymethylene ketone 17. This inter-
mediate underwent acid-catalyzed condensation with 13
and NH4OAc to give heptacyclic terpyridyl 20 in 33%
yield. Reaction of ketone 13 with NaH and 17, followed
by NH4OAc, gave 20 in higher yield. An alternative
synthesis of 20 involved the reaction of â-dimethylamino
(18) (a) Weiss, M. J . Am. Chem. Soc. 1952, 74, 200-202. (b)
Cologne, J .; Dreux, J .; Delplace, H. Bull. Soc. Chim. Fr. 1957, 447-
449. (c) Hall, G. E.; Walker, J . J . Chem. Soc. 1968, 2237-2244. (d)
Thummel, R. P.; J ahng, Y. J . Org. Chem. 1985, 50, 2407-2412. (e)
Tilichenko, M. N.; Koroleva-Vasil′eva, I. A.; Akimora, T. I. Zh. Org.
Khim. (Engl. Trans.) 1986, 22, 1725-1727.
(19) Bell, T. W.; Rothenberger, S. D. Tetrahedron Lett. 1987, 28,
4817-4820.
(20) Gill, N. S.; J ames, K. B.; Lions, F.; Potts, K. T. J . Am. Chem.
Soc. 1952, 74, 4923-4928.
(21) (a) Monson, R. S. J . Heterocycl. Chem. 1976, 13, 893-895. (b)
Cordonnier, G.; Sliwa, H. J . Heterocycl. Chem. 1987, 24, 111-115.
(22) (a) Boekelheide, V.; Linn, W. J . J . Am. Chem. Soc. 1954, 76,
1286-1291. (b) Cohen, T.; Deets, G. L. J . Am. Chem. Soc. 1972, 94,
932-938. (c) McKillop, A.; Bhagrath, M. K. Heterocycles 1985, 23,
1697-1701. (d) Klimov, G. A.; Tilichenko, M. N. Khim. Geterotsikl.
Soedin., Sb. 1: Azotsoderzhashchie Geterotsikly 1967, 306-309 (Chem.
Abstr. 1969, 70, 87539z. (e) Fontenas, C.; Bejan, E.; Haddou, H. A.;
Balavoine, G. G. A. Synth. Commun. 1995, 25, 629-633.
(23) J o¨ssang-Yanagida, A.; Gansser, C. J . Heterocycl. Chem. 1978,
15, 249-251.
(24) Omura, K.; Swern, P. Tetrahedron 1978, 34, 1651-1660.
(25) (a) Lodde, N.; Reimann, E. Arch. Pharm. (Weinheim) 1977, 312,
940-950. (b) Thummel, R. P.; Lefoulon, F.; Cantu, D.; Mahadevan,
R. J . Org. Chem. 1984, 49, 2208-2212.
(26) A lower-yield synthesis of 4-benzylidene-9-methyl-1,2,3,4,5,6,7,8-
octahydroacridine (the methyl analogue of 15) in two steps from the
methyl analogue of 7 has been reported: Minaeva, N. N.; Tilichenko,
M. N. Zh. Org. Khim. (Engl. Trans.) 1986, 22, 1720-1724.
(27) Ransohoff, J . E. B.; Staab, H. A. Tetrahedron Lett. 1985, 26,
6179-6182.

Heptacyclic Terpyridyl Molecular Clefts
J . Org. Chem., Vol. 63, No. 7, 1998 2235
Sch em e 4a
Sch em e 5a
enone 18, prepared by condensation of ketone 13 with
Bredereck’s reagent,28 with 13 and NH4BF4. Though
limited to synthesis of symmetrical pyridines, the tri-
methylhydrazonium tetrafluoroborate pyrolysis method29
provided the simplest synthesis of 20 from ketone 13.
Quaternization of dimethylhydrazone 19 with trimethyl-
oxonium BF4 (rather than methyl iodide29) generated
-
the pyrolysis precursor directly, saving an anion ex-
change step. Batch pyrolysis of 19 yielded 20 in 23%
yield overall from 13.13a
tried, including the following: acetic anhydride,34 oxalyl
chloride,24,33,35 DCC,36 P2O5,37 trifluoroacetic anhydride,38
and phenyl dichlorophosphate.39 The best results were
obtained with the methods of Swern (oxalyl chloride)35
and Albright-Goldman (acetic anhydride).34 Yields ex-
ceeded 90% with the Swern oxidation, but the latter
procedure is better suited to large-scale reactions, since
it can be conducted at room temperature and is not very
sensitive to the presence of water. Recrystallization
removes side products, consisting mainly of 21 and the
(methylthio)methyl ether corresponding to alcohol 22.
The Newkome-Fishel pyrolysis method29 used for
synthesis of heptacyclic terpyridyl 20 (Scheme 3) was also
applied successfully to dibenzylidene analogue 26 (Scheme
5). Dimethylhydrazone 24 was quaternized with tri-
methyloxonium BF4- and the trimethylhydrazonium salt
25 was pyrolyzed to give 26. Attempts to scale-up batch
reactions produced 26 in lower yields, apparently because
of less efficient removal of volatile byproducts. To
overcome this problem, a flow system was developed in
which a solution of 25 was added slowly to an inclined,
heated tube through which N2 was passed. Recrystalli-
zation of the crude product gave 26 in higher, though
variable, yield. The yield of pure 26 was reproducibly
Synthesis of pentadentate cleft 6 requires functional-
ization of both OHA components at both CH2 groups
nearest to nitrogen (positions 4 and 5). One strategy
would be to oxidize heptacyclic terpyridyl 20 to diketone
6, or masked carbonyl groups could be introduced prior
to coupling the OHA units. The latter approach could
shorten the overall synthesis because benzaldehyde
condensation and N-oxide rearrangement can be com-
bined in one step.30 N-Oxide 11 is first heated in acetic
anhydride, then benzaldehyde is added to form ben-
zylideneacetate 21 (Scheme 4).7a Acidic hydrolysis yields
benzylidene alcohol 22, previously isolated as its H2SO4
salt.7a The procedure has been modified for large scale
and ease of separation of 22 from side products, consist-
ing mainly of 14. Hydrolysis of 21 with aqueous HBr
and recrystallization of 22‚HBr affords pure product in
higher yield than previously obtained with 22‚H2SO4
(43%).7a Oxidation of alcohol 22 to ketone 23 was
previously carried out in high yield with Dess-Martin
periodinane.31 This hypervalent iodine reagent is report-
edly explosive,32 so alternative methods were sought for
large-scale reactions. The CrO3/H2SO4 procedure used
for conversion of 12‚H2SO4 to 13 was not successful,
probably because of the low solubility of 22‚H2SO4.
Several activated DMSO oxidation methods33-39 were
(28) Abdulla, R. F.; Brinkmayer, R. S. Tetrahedron 1979, 35, 1675-
1735.
(29) Newkome, G. R.; Fishel, D. L. J . Org. Chem. 1972, 37, 1329-
1336.
(30) Klimov, G. A.; Tilichenko, M. N. Khim. Geterotsikl. Soedin.
(Engl. Trans.) 1969, 5, 133-134.
(31) Dess, D. B.; Martin, J . C. J . Org. Chem. 1983, 48, 4156-4158
Caution: Dess-Martin periodinane is explosive (ref 32).
(32) Plumb, J . B.; Harper, D. J . Chem., Eng. News 1990, J uly 16, 3.
(33) Mancuso, A. J .; Swern, D. Synthesis 1981, 165-185.
(34) Albright, J . D.; Goldman, L. J . Am. Chem. Soc. 1967, 89, 2416-
2423.
(36) (a) Pfitzner, K. E.; Moffatt, J . G. J . Am. Chem. Soc. 1963, 85,
3027-3028. (b) Pfitzner, K. E.; Moffatt, J . G. J . Am. Chem. Soc. 1965,
87, 5670-5678.
(37) (a) Onodera, K.; Hirano, S.; Kashimura, N. J . Am. Chem. Soc.
1965, 87, 4651-4652. (b) Georges, M.; Fraser-Reid, B. J . Org. Chem.
1985, 50, 5754-5758. (c) Taber, D. F.; Amedio, J . C.; J ung, K.-Y. J .
Org. Chem. 1987, 52, 5621-5622.
(38) (a) Omura, K.; Sharma, A. K.; Swern, D. J . Org. Chem. 1976,
41, 957-962. (b) Huang, S. L.; Omura, K.; Swern, D. J . Org. Chem.
1976, 41, 3329-3331. (c) Huang, S. L.; Omura, K.; Swern, D. Synthesis
1978, 297-299.
(39) Liu, H.-J .; Nyangulu, J . M. Tetrahedron Lett. 1988, 29, 3167-
3170.
(35) Mancuso, A. J .; Huang, S.-L.; Swern, D. J . Org. Chem. 1978,
43, 2480-2482.

2236 J . Org. Chem., Vol. 63, No. 7, 1998
Bell et al.
Sch em e 6a
F igu r e 2. Formation of heptacyclic terpyridyl derivative 26
and side products 31 and 33 in coupling reaction between
Manich base 27 and ketone 23.
improved by treatment of the crude product with hy-
droxylamine hydrochloride. The synthesis of 26 was
greatly improved with Mannich salt 27‚HCl. Despite the
previous failure of several methods for preparation of
Mannich bases40 from 23, reaction with N,N-dimethyl-
(methylene)immonium chloride41 in acetonitrile effi-
ciently gave 27‚HCl. Either 27‚HCl or free base 27 could
be condensed with ketone 23 and NH4OAc by variations
of the method of Risch et al.42 The best yields of 26 were
obtained when the reaction was conducted in hot DMSO
or pyridine and when ketone 23 was treated with
NH4OAc prior to addition of the Mannich base or salt.
Oxidants (Cu(OAc)2, DDQ, Ag2O, or Hg(OAc)2) did not
significantly improve the yield of 26, despite the required
intermediacy of a dihydropyridine. The R-methylene
ketone (29) was prepared efficiently from 27 by reaction
with methyl iodide, followed by triethylamine, but 29
reacted with ketone 23 to give 26 in yields comparable
to those of reactions in which this enone was formed in
situ from 27 or 27‚HCl.
improved yield of 26 when 23 was preheated with
NH4OAc. In this case, imine 30 is apparently formed,
and the concentration of NH4OAc is minimized. Enone
29, formed by elimination of dimethylamine from 27, is
then trapped more efficiently by reaction with the enam-
ine tautomer of 30. Unsymmetrical terpyridyl 33 ap-
parently results from condensation of ketone 23 with
â-amino enone 32, which is produced by conjugate
addition of ammonia to 29. Pretreatment of 23 with
NH4OAc reduces the yields of both 31 and 33, indicating
that 33 is not produced from 30 by nucleophilic attack
of the imine nitrogen atom at the â-carbon of enone 29.
Similar S-shaped terpyridyls were isolated by Risch et
al.42d in a study of Mannich condensations of 6,7-dihy-
roquinolin-8(5H)-one with substituted iminium salts, but
the role of regioselectivity in the reaction of ammonia
with enone intermediates was not discussed.
Diketone 6 was synthesized by two different routes
(Scheme 6). Following Thummel’s observation that the
terminal rings of 2,2′;6′,6′′-terpyridine undergo N-oxida-
tion prior to the central ring,43 we treated heptacyclic
terpyridyl 20 with MCPBA. Crude di-N-oxide 34 under-
went Boekelheide rearrangement,22 and the resulting
diacetate was hydrolyzed to a diastereomeric mixture of
diols (35). Oxidation of 35 with Dess-Martin periodi-
nane31 gave diketone 6 in 35% yield overall from 20.
Ozonolysis of dibenzylidene compound 26 gave 6 more
efficiently (>90%) and in higher purity than by the
former route. Diketone 6 adsorbs strongly to silica gel
and alumina in the absence of metal salts. Addition of
2% KI to a 95% ethanol eluent moved 6 off the baseline
during TLC on alumina or silica plates; 6 could be
As a result of efforts to improve the synthesis of 26,
two significant side products were isolated and identified
from Mannich condensations: 31, the spiro-dimer of
enone 29 and unsymmetrical S-shaped terpyridyl 33
(Figure 2). Enone dimer 31 was also produced in control
experiments in which 27 was heated in DMSO with or
without NH4OAc. The pathways presented in Figure 2
account for the formation of these products and for the
(40) Review: Tramontini, M.; Angiolini, L. Tetrahedron 1990, 46,
1791-1837.
(41) (a) Kinast, G.; Tietze, L.-F. Angew. Chem., Int. Ed. Engl. 1976,
15, 239-240. (b) Rochin, C.; Babot, O.; Dunogues, J .; Duboudin, F.
Synthesis 1986, 228-229.
(42) (a) Risch, N.; Esser, A. Synthesis 1988, 337-339. (b) Wester-
welle, U.; Esser, A.; Risch, N. Chem. Ber. 1991, 124, 571-576. (c)
Risch, N.; Esser, A. Liebigs Ann. 1992, 233-237. (d) Keuper, R.; Risch,
N.; Flo¨rke, U.; Haupt, H.-J . Liebigs Ann. 1996, 705-715. (e) Keuper,
R.; Risch, N. Liebigs Ann. 1996, 717-723.
(43) Thummel, R. P.; J ahng, Y. J . Org. Chem. 1985, 50, 3635-3636.

Heptacyclic Terpyridyl Molecular Clefts
J . Org. Chem., Vol. 63, No. 7, 1998 2237
Sch em e 7a
Ta ble 1. Sta bility Con sta n ts (log Ks) of Com p lexes
betw een Hosts a n d Alk a li Meta l P icr a tes in
a
H2O-Sa tu r a ted CHCl3
host
Li
Na
9.7
4.7
<8
6.1
K
Rb
8.9
4.3
<3
7.1
Cs
8.1
4.1
<3
6.1
6
20
8.3
5.2
<3
4.4
9.5
4.7
<3
7.9
37
38b
a
The method for estimation of Ks values is described in ref 46.
b
Reference 46b.
picrate extraction method.46 Stability constants of the
1:1 complexes were calculated assuming the absence of
any other equilibria in the water-saturated organic phase
competing with that represented by eq 1; the results are
given in Table 1. Extraction experiments employing
flexible terpyridyl 37 did not produce detectible concen-
trations of picrate in the organic phase, so the stability
constants of the alkali metal complexes of 37 cannot
exceed 103 M-1. For purpose of comparison, the stability
constants of alkali metal picrate complexes of 2,3-
naphtho-18-crown-6 (38)46b are also given in Table 1.
isolated from the ozonolysis product mixture by addition
of Ca(OTf)2 and chromatography of the 1:1 complex.
For comparison of complexation properties of preorga-
nized and flexible terpyridyls, 2,6-bis(5,6,7,8-tetrahydro-
quinol-2-yl)pyridine (37) was prepared by an effective
synthesis of terpyridyls from ketones.44 As shown in
Scheme 7, 2,6-diacetylpyridine was treated with Bred-
ereck’s reagent to afford bis(â-dimethylamino enone) 36.
This compound has also been synthesized by reaction of
2,6-diacetylpyridine with DMF dimethylacetal.45 Reac-
tion of 36 with cyclohexanone enolate, followed by
NH4OAc, gave 37. This sequence demonstrates that
J ameson’s terpyridine synthesis44 can be extended from
methyl ketones to cyclohexanones and that two pyridine
rings can be formed in one step in useful yield.
Com p lexa tion . Increased chromatographic mobility
of diketone 6 in the presence of KI and Ca(OTf)2 suggests
that the preorganized cleft of the free ligand has high
charge density. The TLC behavior of 6 is opposite that
of many host compounds, such as crown ethers, which
have higher Rf values as metal-free ligands than as alkali
or alkaline earth metal complexes. Strong complexation
of a cation apparently reduces the negative charge
density of the cleft, and adsorption of the resulting
complex is weak in the presence of a lipophilic anion. An
alternative explanation is that metal-free 6 is protonated
during chromatography and that the resulting salt is
more polar than the metal complexes. Sodium and
potassium picrate complexes were prepared by extraction
of the picrate salts from water into CHCl3 solutions of 6.
The presence of Na2CO3 or K2CO3 in the aqueous layers
gave the purest samples of complexes, apparently be-
cause host protonation is suppressed. The recrystallized
6‚Na(picrate) and 6‚K(picrate) complexes have 1:1 sto-
ichiometries, while the Ca(OTf)2 complex isolated had 2:1
stoichiometry. Crystals of this complex were not of
sufficient quality to allow crystallographic investigation
of its structure, but the symmetry exhibited by its 1H
NMR spectrum suggests that the two molecules of 6 bind
calcium by an equal number of metal-ligand interac-
tions. They may lie in perpendicular or parallel planes,
binding calcium in interlocked or stacked arrangements,
respectively.
Ks
H + G+ 98 H‚G+
(1)
The Ks values for alkali metal complexes of heptacyclic
terpyridines 6 and 20 are remarkably high for hosts
containing five and three ligand atoms, respectively.
Stability constants reported for comparable crown ether
complexes containing 5-6 ligating sites generally range
from 104-109 M-1, as exemplified by results for 2,3-
naphtho-18-crown-6 (38) given in Table 1. In water-
saturated chloroform, pentadentate host 6 binds Na+ and
K+ more strongly than do most crown ethers.3j,47 Even
tridentate host 20 extracts alkali metal picrates into
chloroform, whereas model system 37 is ineffective under
the same experimental conditions. Compared with 20,
37 lacks two butyl chains as well as two six-membered
rings. Preorganization of three pyridine rings in 20
might be expected to have a larger effect than substitu-
tion of the pyridine rings with alkyl groups. The potent
complexation ability of heptacyclic terpyridyl hosts can
be attributed to enforced orientation of relatively large
ligand functional group dipoles48 toward the center of the
molecular cleft.
Heptacyclic terpyridyl host 6 is somewhat selective for
Na+ and K+ relative to Li+, Rb+, and Cs+, but its
selectivity curve is relatively flat compared with those
of typical crown ethers and cryptands.47 Tridentate cleft
20 shows measurable selectivity for Li+, but the Ks values
of the strongest and weakest complexes vary by only 1
(46) (a) Koenig. K. E.; Lein, G. M.; Stu¨ckler, P.; Kaneda, T.; Cram,
D. J . J . Am. Chem. Soc. 1979, 101, 3553-3566. (b) Helgeson, R. C.;
Weisman, G. R.; Toner, J . L.; Tarnowski, T. L.; Chao, Y.; Mayer, J .
M.; Cram. D. J . J . Am. Chem. Soc. 1979, 101, 4928-4941.
(47) Reviews: (a) Izatt, R. M.; Bradshaw, J . S.; Nielsen, S. A.; Lamb,
J . D.; Christensen, J . J . Chem. Rev. 1985, 85, 271-339. (b) Izatt, R.
M.; Pawlak, K.; Bradshaw, J . S.; Bruening, R. L. Chem. Rev. 1991,
91, 1721-2085.
Solution stabilities of the alkali metal complexes of
heptacyclic terpyridyls 6 and 20 were estimated by the
(44) J ameson, D. L.; Guise, L. E. Tetrahedron Lett. 1991, 32, 1999-
2002.
(45) Bejan, E.; Haddou, E. A.; Daran, J . C.; Balavoine, G. G. A.
Synthesis 1996, 1012-1018.
(48) The dipole moments of pyridine and acetone are 2.2 and 2.9 D,
respectively: Weast, R. C.; Ed. CRC Handbook of Chemistry and
Physics; CRC Press: Boca Raton, FL, 1988; pp E58-60.

2238 J . Org. Chem., Vol. 63, No. 7, 1998
Bell et al.
was extracted with 20 mL of ether. The organic layer was
dried over K2SO4 and concentrated to minimum volume in
vacuo (25-35 mm). The resulting yellow solid was recrystal-
lized from hexane to afford 1,2,3,4,5,6,7,8-octahydroxanthen-
9-one (10) as yellow crystals (0.88 g, 72%), mp 130-131 °C
(lit.21b 131 °C). Of this product, 0.5 g (2.5 mmol) was placed
in a flask equipped with a rubber septum. The flask was
flushed thoroughly with nitrogen, and freshly distilled anhy-
drous THF (10 mL) was added by syringe. The resulting
solution was stirred at 0 °C as 2.2 mL of a 1.34 M solution of
n-butyllithium in hexane was added dropwise. Stirring was
continued at 0 °C for 3 h after addition was complete. Reaction
was quenched by addition of 0.6 mL of acetic acid, and the
resulting solution was warmed to room temperature. THF was
removed at reduced pressure, and 0.2 g of NH4OAc (2.6 mmol)
and 4 mL of acetic acid were added. The resulting solution
was heated at reflux for 2 h and then cooled to room
temperature. The mixture was diluted with 10 mL of water,
basified (pH 14) with 2 M aqueous NaOH, and extracted with
ether (20 mL). The extract was dried (MgSO4) and filtered,
and the filtrate was concentrated by rotary evaporation to yield
0.6 g (95%) of the desired product as a beige solid, mp 36-37
°C (lit.13c 41-43 °C).
order of magnitude. These trends parallel the poor
discrimination between alkali metals observed for torand
5.7c The general conclusions are the same as for torand
5: strong complexation can be achieved with relatively
planar preorganized hosts that do not encapsulate the
guest; however, encapsulation may be needed for selec-
tivity toward a series of spherical guests of varying radii.
Further interpretation of these results must await more
detailed thermodynamic and structural investigation of
these complexes.
Exp er im en ta l Section
Gen er a l Meth od s. All reactions were conducted under an
atmosphere of dry N2 unless otherwise indicated. Reagent
grade solvents were used without purification. Anhydrous
solvents were purified as follows: DMSO was distilled from
CaH2 under reduced pressure and collected over activated 4A
molecular sieves; CH2Cl2, pyridine, and benzene were distilled
from CaH2 under N2; THF was distilled from Na and ben-
zophenone; acetic anhydride was dried over P2O5 and then
distilled under reduced pressure.
9-Bu tyl-1,2,3,4,5,6,7,8-octa h yd r oa cr id in e N-Oxid e (11).
The following modification of the published procedure13c was
employed. A 3 L flask equipped with a mechanical stirrer and
reflux condenser fitted with a nitrogen inlet tube was charged
with 76 g (0.32 mol) of 9-butyl-1,2,3,4,5,6,7,8-octahydroacri-
dine, 144 g (0.24 mol) of Oxone, 57 g (0.68 mol) of NaHCO3,
1.6 L of methanol, and 480 mL of distilled water. The resulting
suspension was stirred at 45-50 °C under nitrogen for 24 h.
The inorganic salts were removed from the cooled reaction
mixture by vacuum filtration and washed with CH2Cl2 (2 ×
100 mL). Solvents were removed from the combined filtrates
by rotary evaporation and the resulting white suspension was
extracted with CH2Cl2 (3 × 100 mL). The combined extracts
were washed with water (2 × 100 mL) and dried using MgSO4.
Filtration and removal of CH2Cl2 by rotary evaporation yielded
a pale yellow oil. Residual solvent was removed in vacuo (0.5
mm), yielding 80 g (97%) of 11 as a pale yellow, waxy solid,
mp 98-99 °C (lit.13c 92-94 °C). 13C NMR (75 MHz, CDCl3) δ
145.3, 137.4, 129.9, 30.7, 27.4, 25.7, 25.4, 23.1, 22.2, 21.8, 13.7.
9-Bu t yl-2,3,5,6,7,8-h exa h yd r oa cr id in -4(1H )-on e (13).
Meth od A. A solution of 3.5 mL (40 mmol) of oxalyl chloride
(Aldrich, 98%) in 100 mL of anhydrous CH2Cl2 was stirred
under N2 at -78 °C as 5.8 mL (81 mmol) of anhydrous DMSO
was added by syringe. The resulting mixture was stirred for
30 m at -78 °C, and then a solution of 7.0 g (27 mmol) of
9-butyl-1,2,3,4,5,6,7,8-octahydroacridin-4-ol (12)13 in 20 mL of
CH2Cl2 was added dropwise. The viscous reaction mixture was
stirred for 30 min at -78 °C, 17 mL (0.12 mol) of triethylamine
was added, and the cooling bath was removed. The reaction
mixture was allowed to warm to room temperature, poured
into 25 mL of water, and extracted with CH2Cl2 (2 × 25 mL).
The combined extracts were washed with pH 7 buffer (3 ×
100 mL), dried over Na2SO4, and concentrated in vacuo to give
7.8 g of a brown oil. This oil was dissolved in 30 mL of
hexanes/ethyl acetate (1:1, v/v) and filtered through 75 g of
basic alumina (Fisher, activity I, 80-100 mesh), washing the
alumina with additional 1:1 hexane/ethyl acetate. Rotary
evaporation gave a yellow oil that solidified on standing in
vacuo, yielding 6.75 g (97%) of an off-white solid, mp 64-65
°C. An analytical sample was obtained as a pale orange oil
by bulb-to-bulb distillation at 145-150 °C (0.1 mm). 1H NMR
(300 MHz, CDCl3) δ 3.01 (m, 2 H), 2.92 (t, J ) 6 Hz, 2 H), 2.75
(m, 4 H), 2.61 (t, J ) 6 Hz, 2 H), 2.15 (m, 2 H), 1.85 (m, 4 H),
1.45 (m, 4 H), 0.98 (t, J ) 7 Hz, 3 H); 13C NMR (75 M Hz,
CDCl3) δ 197.2 (CdO), 156.2, 148.5, 144.9, 136.0, 134.4, 38.9,
33.0, 30.0, 27.6, 25.9, 25.1, 22.9, 22.3, 22.13, 22.05, 13.4; IR
(KBr) 2950 (s), 2850 (s), 1690 (s), 1560 (s), 1450 (m), 1430 (s),
1340 (m), 1320 (m), 1290 (m), 1240 (s), 1160 (s), 1120 (m), 940
(m), 910 (m), 740 (s); GCMS (70 eV) m/z (rel int) 257 (100,
M+), 242 (35, M - CH3), 228 (63, M - C2H5), 214 (46, M -
C3H7), 200 (80, M - C4H7). Anal. Calcd for C17H23NO: C,
79.33; H, 9.01; N, 5.44. Found: C, 79.38; H, 8.88; N, 5.19.
Melting points are uncorrected. All NMR chemical shifts
were measured relative to solvent resonances as indicated and
are reported in δ values (ppm); coupling constants are reported
in Hz. Infrared frequencies are reported in units of cm-1. UV-
visible wavelengths are reported in units of nm. Electron
impact mass spectra were recorded at 70 eV. Fast atom
bombardment mass spectra were obtained using a m-nitroben-
zyl alcohol matrix.
9-Bu tyl-2-h ydr oxytr icyclo[7.2.1.02,7]tr idecan -13-on e (7).
The condensation of cyclohexanone with n-pentanal was
conducted according to the published procedure.13 Recrystal-
lization was carried out by dissolving each gram of crude
product in 3 mL of hot methanol, boiling until cloudiness
occurred and cooling slowly to 0 °C. The white, crystalline
product was dried: mp 140-141 °C (lit.13c 141-142 °C); 13C
NMR (75 MHz, CDCl3) δ 207.4 (CdO), 77.9 (COH), 59.4, 48.2,
44.8, 42.1, 36.4, 29.1, 28.8, 28.5, 28.2, 26.1, 25.2, 22.5, 20.9,
20.1, 13.7.
8-Bu tyltr icyclo[7.3.1.02,7]tr id ec-2(7)-en -13-on e (8).
A
mixture of 4.78 g (18.1 mmol) of keto alcohol 7 and 0.2 mL of
a 0.1 M solution of p-toluenesulfonic acid monohydrate in
ethanol was heated at 210 °C under vacuum (0.1 mm) with
distillation of the product through a 16 cm Vigreux column
(bp 120-130 °C). Thus 2.59 g (58%) of â,γ-enone 8 was
obtained, which crystallized upon standing. An analytical
sample was obtained by recrystallization from methanol, mp
52 °C. 1H NMR (80 MHz, CDCl3) δ 2.5 (m, 1 H), 1.9-2.3 (m,
6 H), 1.1-1.9 (m, 16 H), 0.89 (t, J ) 6, 3 H); IR (neat) 2930
(s), 2850 (s), 1720 (s), 1680 (s), 1460 (m), 1450 (s), 1390 (s),
1280 (m), 1200 (s), 1160 (m), 1130 (s), 1120 (m), 980 (m), 910
(m), 880 (m); MS (70 eV) m/z (rel int) 246 (0.2, M+), 189 (100,
M - C4H9). Anal. Calcd for C17H26O: C, 82.87; H, 10.63.
Found: C, 83.01; H, 10.63.
9-Bu tyl-1,2,3,4,5,6,7,8-octa h yd r oa cr id in e (9). Meth od
A. The published procedure13 was used to convert 200 g (0.76
mol) of 7 to 173-177 g (91-96%) of 9, mp 36-38 °C (lit.13c
41-43 °C). 13C NMR (75 MHz, CDCl3) δ 153.5, 148.2, 127.2,
33.0, 30.3, 27.6, 25.6, 23.3, 23.1 22.9, 13.7.
Meth od B. A mixture of 1.0 g (6 mmol) of 1-morpholinocy-
clohexene,49,50 1.02 g (6.0 mmol) of 2-carbethoxycyclohexanone,
and 10 mL of anhydrous xylene was heated under nitrogen at
170 °C for 72 h. The reaction mixture was cooled and solvents
were removed in vacuo (1 mm). The resulting yellow oil was
diluted with 15 mL of 40% aqueous sodium metabisulfite and
5 mL of ethanol and stirred at room temperature for 1 h. The
resulting solids were removed by filtration, and the filtrate
(49) Hu¨nig, S.; Lu¨cke, E.; Brenninger, W. Organic Syntheses;
Baumgarten, H. E., Ed.; Wiley: New York, 1973; Coll. Vol. V, pp 808-
809.
(50) Roelofsen, D. P.; van Bekkum, H. Rec. Trav. Chim. 1972, 91,
605-610.

Heptacyclic Terpyridyl Molecular Clefts
J . Org. Chem., Vol. 63, No. 7, 1998 2239
Meth od B. A solution of CrO3 in 2:1 (v/v) acetic acid/water
(6.0 mL, 24 mmol of CrO3) was added dropwise over 3 min to
a rapidly stirred solution of 7.78 g (30 mmol) of 9-butyl-
1,2,3,4,5,6,7,8-octahydroacridin-4-ol (12) and 6 mL of concen-
trated sulfuric acid in 54 mL of glacial acetic acid. The
reaction mixture was stirred for 2 h and then diluted with 500
mL of 2 M aqueous sodium acetate and extracted with CHCl3
(3 × 110 mL). The combined extracts were washed with 5%
aqueous NaHCO3, dried over Na2SO4, and concentrated by
rotary evaporation to a red-brown oil. The crude product was
dissolved in CH2Cl2 and filtered through 100 g of basic alumina
(activity II), eluting with 94:6 CH2Cl2/acetone. Rotary evapo-
ration gave 7.31 g (95%) of ketone 13 as a light brown oil,
which could be further purified as described in method A.
Meth od C. A solution of 9.16 g (37.7 mmol) of 9-butyl-
1,2,3,4,5,6,7,8-octahydroacridine (9) and 1.50 mL (14.7 mmol)
of benzaldehyde in 18 mL of acetic anhydride was heated
under N2 at 155-160 °C for 16.5 h. Most of the acetic
anhydride was removed by distillation in vacuo (25-35 mm),
and the residue was dissolved in 20 mL of CHCl3. The
resulting solution was washed with 100 mL of 1 M aqueous
NaOH, and the aqueous layer was extracted with CHCl3 (2 ×
5 mL). The combined organic solutions were distilled under
vacuum through a 8 cm Vigreux column, yielding 5.12 g of
recovered starting material, bp 120-130 °C (0.2 mm). The
residue was dissolved in 12.6 g of acetone, and 2.05 g of
concentrated sulfuric acid was added with stirring to precipi-
tate the product. The resulting mixture was stored overnight
in a refrigerator. The precipitate was collected by filtration,
washed with acetone, and dried in vacuo to yield 4.59 g (63%)
drate in 20 mL of ethanol was heated at reflux for 15 min.
The reaction mixture was cooled, diluted with ether, washed
with pH 7 buffer (2 × 40 mL) and saturated aqueous NaCl
(25 mL), and then dried over MgSO4. Rotary evaporation gave
0.12 g (86%) of ethoxymethylene ketone 17 as a light yellow-
brown oil that partially crystallized on standing and slowly
decomposed upon exposure to air. A mixture of 38 mg (0.15
mmol) of ketone 13, 42 mg (0.13 mmol) of ethoxymethylene
ketone 17, 20 mg (0.8 mmol) of NaH, 0.06 mL of ethanol, and
2 mL of anhydrous THF was stirred at room temperature for
19 h. Solvents were removed by rotary evaporation and the
residue was dissolved in 10 mL of acetic acid with 0.52 g (6.8
mmol) of ammonium acetate. The resulting solution was
stirred under reflux for 7.5 h and then concentrated to dryness
by rotary evaporation. The residue was triturated with 2 M
aqueous NaOH and extracted with CHCl3 (2 × 2 mL). The
combined extracts were dried (MgSO4) and rotary evaporated,
leaving a glassy orange-brown residue. Chromatography with
neutral alumina (activity grade II), eluting with CH2Cl2/ethyl
acetate (1:1, v/v) gave 31 mg (43%) of 20 as straw-colored
crystals.
Meth od B. A mixture of 2.82 g (11.0 mmol) of ketone 13
and 4.0 mL of tert-butoxybis(dimethylamino)methane (Bred-
ereck’s reagent, Aldrich) was heated at 70 °C for 3 h. The
cooled mixture was diluted with benzene and washed with 50
mL of 5% aqueous NaHCO3 and then with 50 mL of pH 7
buffer. Rotary evaporation gave 3.14 g (92%) of crude 18 as a
brown oil, which can be purified by chromatography on silica
gel, eluting with benzene/ethanol/triethylamine (85:15:15, v/v).
1H NMR (80 MHz, CDCl3) δ 7.70 (s, 1 H), 3.10 (s, 6 H), 2.5-
3.4 (m, 10 H), 1.7-1.9 (m, 4 H), 1.3-1.5 (m, 4 H), 0.96 (t, J )
6 Hz, 3 H). MS (70 eV) m/z (rel int) 312 (54, M+), 311 (35, M
- 1), 197 (30, M - CH3), 268 (76, M - NMe2). A solution of
2.45 g (9.5 mmol) of ketone 13, 3.14 g (10.1 mmol) of crude 18
and 5 g (50 mmol) of ammonium tetrafluoroborate in 15 mL
of dimethylformamide was stirred at 150 °C for 15 min. An
additional 1 g (10 mmol) of ammonium tetrafluoroborate was
added, and the reaction mixture was stirred a further 65 min
at 150 °C. The cooled reaction mixture was diluted with 150
mL of benzene/chloroform (9:1, v/v), washed with 0.5 M
aqueous NaOH (2 × 200 mL), and dried over MgSO4. Rotary
evaporation left a dark brown glass that was dissolved in ethyl
acetate. After standing for several hours, this solution was
filtered to collect a precipitate, which was washed with ethyl
acetate. The solid was dissolved in CH2Cl2, and a small
amount of undissolved material was removed by filtration. The
filtrate was rotary evaporated, and the residue was recrystal-
lized from ethanol to give 1.31 g (26%) of 20 as yellow-orange
needles.
1
of 15‚H2SO4, H NMR (80 MHz, CDCl3) δ 7.81 (s, 1 H), 7.2-
7.5 (m, 5 H), 3.40 (m, 2 H), 2.6-2.9 (m, 8 H), 1.75-1.90 (m, 6
H), 1.3-1.5 (m, 4 H), 0.99 (t, J ) 6 Hz, 3 H). This salt was
converted to the free base by reaction with 50 mL of 2 M
aqueous NaOH and extraction with CHCl3. The combined
extracts were washed with saturated aqueous NaCl, dried
(MgSO4), and evaporated. A solution of 2.29 g (6.9 mmol) of
15 in 11 mL of CHCl2/methanol (3:1, v/v) was cooled to -42
°C by means of a CH3CN/CO2 slush bath. An ozone/oxygen
mixture was bubbled through the solution for 2.5 h, and then
the solution was purged of ozone by bubbling with N2 for 1 h.
Dimethyl sulfide (1 mL) was added, and the resulting mixture
was stored at room temperature for 18 h. Solvents were
removed by rotary evaporation, and then the residue was
heated at 70-80 °C under vacuum (0.1-1 mm). The crude
product was chromatographed on 200 g of silica gel, eluting
with CH2Cl2/methanol (9:1, v/v), yielding 1.46 g (82%) of ketone
13 as an orange-brown oil.
9-Bu t yl-3-(h yd r oxym et h ylen e)-2,3,5,6,7,8-h exa h yd r o-
a cr id in -4(1H)-on e (16). To a solution of 1.10 g (4.3 mmol)
of ketone 13 in 15 mL of anhydrous THF were added 0.30 g
(12 mmol) of NaH, 0.6 mL (10 mmol) of ethanol, and 1.5 mL
(19 mmol) of ethyl formate. The reaction mixture was stirred
for 12 h at room temperature, and then solvents were removed
by rotary evaporation. The residue was triturated with several
portions of pH 7 buffer (125 mL total, 0.25 M capacity) and
extracted with CHCl3 (2 × 5 mL). The combined extracts were
dried (MgSO4) and evaporated to give 1.21 g of brown oil that
rapidly crystallized. Recrystallization from 10 mL of cyclo-
hexane gave 0.73 g (60%) of 16 as reddish-brown needles. An
analytical sample was obtained by filtration of an ethyl acetate
solution through silica gel followed by recrystallization from
cyclohexane, mp 118-119 °C. 1H NMR (80 MHz, CDCl3) δ
9.85 (bs, 1 H), 2.5-3.0 (m, 10 H), 1.7-1.9 (m, 4 H), 1.3-1.5
(m, 4 H), 0.97 (t, J ) 6 Hz, 3 H); IR (KBr) 3210 (s), 2940 (s),
2860 (s), 1660 (m), 1650 (s, CdO), 1570 (s), 1570 (s), 1450 (s),
1415 (s), 1385 (s), 1340 (s), 1280 (m), 1240 (m), 1185 (s), 1110
(m), 990 (s), 905 (m), 890 (m), 830 (m), 820 (m), 735 (s), 670
(s). UV-Vis (CH3OH, ꢀ × 10-3) λmax 236 (10.7), 240 (10.7), 271
(4.1), 281 (4.3), 340 (22.0). Anal. Calcd for C18H23NO2: C,
75.76; H, 8.12; N, 4.96. Found: C, 75.77; H, 8.24; N, 4.83.
5,11-Dibu tyl-1,2,3,4,6,7,9,10,12,13,14,15-dodecah ydr oacr i-
d in o[4,3-b]ben zo[j][1,10]p h en a n th r olin e (20). Meth od A.
A solution of 0.11 g (0.39 mmol) of hydroxymethylene ketone
16 and 92 mg (0.48 mmol) of p-toluenesulfonic acid monohy-
Meth od C. A solution of 4.76 g (18.5 mmol) of ketone 13,
8 mL (105 mmol) of 1,1-dimethylhydrazine, 10 mL of ethanol,
and 30 mL of cyclohexane was stirred at room temperature
for 13 h. Solvents were removed by rotary evaporation, 30
mL of benzene was added, and the solution was dried by
azeotropic distillation using a Dean-Stark apparatus. Rotary
evaporation gave the solid dimethylhydrazone, which was
dissolved in 40 mL of anhydrous CH2Cl2. Trimethyloxonium
tetrafluoroborate (2.73 g, 18.4 mmol) was added, and the
reaction mixture was stirred at room temperature for 25 min.
Dichloromethane was removed by rotary evaporation without
heating, and the flask containing the orange glassy residue of
trimethylhydrazonium salt 19 was placed in a 200 °C oil bath
for 6 min. During this period the viscous pyrolysis mixture,
which was stirred under a stream of N2, turned dark and
evolved gas. A solution of the cooled reaction mixture in 40
mL of CHCl3 was washed with 40 mL of 2 M aqueous NaOH,
dried (MgSO4), and evaporated. The resulting dark glassy
residue was triturated with 20 mL of ethyl acetate, causing
precipitation of the product over a period of 24 h. The solid
was collected by filtration, washed with ethyl acetate, and
recrystallized from ethanol to give 1.15 g (23%) of 20 as straw-
colored needles, mp 220-221 °C. 1H NMR (300 MHz, CDCl3)
δ 7.36 (s, 1 H), 3.15-3.25 (m, 4 H), 2.92 (m, 8 H), 2.86 (bs, 3
H), 2.79 (m, 4 H), 2.64 (t, J ) 6 Hz, 4 H), 1.8-1.9 (m, 8 H),

2240 J . Org. Chem., Vol. 63, No. 7, 1998
Bell et al.
1.35-1.54 (m, 8 H), 0.98 (t, J ) 6 Hz, 3 H). 13C NMR (75 MHz,
CDCl3) δ 155.6, 150.7, 148.4, 147.4, 134.3, 132.8, 130.3, 129.1,
32.4, 30.9, 27.9, 27.5, 26.1, 23.5, 23.1, 23.0, 22.6, 13.8. IR (KBr)
3340 (m), 2950 (s), 2855 (s), 1557 (s), 1432 (m), 1390 (m), 1243
(s), 1140 (m), 960 (m). UV-Vis (95% ethanol, ꢀ × 10-3) λmax
245 (22), 297 (10), 306 (14), 346 (24). MS (70 eV) m/z (rel int)
505 (100, M+). Anal. Calcd for C35H43N3‚(H2O)1.5: C, 78.90;
H, 8.70; N, 7.89. Found: C, 78.73; H, 8.68; N, 7.65.
solution until it became cloudy. The resulting mixture was
allowed to stand at room-temperature overnight, and then the
precipitate was collected by vacuum filtration and washed with
hexane (2 × 100 mL). Drying under vacuum (1 mm) gave 67.1
g (71%) of 23 as a cream-colored solid, mp 120-121 °C. An
analytical sample was obtained by slow evaporation of a
solution in methanol/water (10:1, v/v), mp 121-122 °C. 1H
NMR (300 MHz, CDCl3) δ 8.08 (s, 1 H), 7.31-7.39 (m, 4 H),
7.23 (t, J ) 7 Hz, 1 H), 2.97 (t, J ) 6.2 Hz, 2 H), 2.82-2.88 (m,
4 H), 2.76 (t, J ) 6.3 Hz, 2 H), 2.66 (m, 2 H), 2.16 (m, 2 H),
1.84 (m, 2 H), 1.45 (m, 4 H), 0.98 (t, J ) 7 Hz, 3 H). 13C NMR
(75 MHz, CDCl3) δ 197.3, 152.0, 148.8, 145.6, 137.8, 136.9,
135.3, 134.6, 129.6, 128.2, 127.8, 126.5, 39.4, 30.5, 28.2, 27.4,
26.7, 25.8, 23.2, 22.5, 22.3, 13.8. IR (KBr) 3019 (w), 2947 (s),
2865 (m), 2832 (m), 1698 (s), 1559 (m), 1488 (m), 1443 (m),
1424 (m), 1388 (m), 1335 (m), 1213 (m), 1174 (s), 1134 (m),
966 (m), 766 (m), 701 (s). UV-Vis (CH3OH, ꢀ × 10-3) λmax
223 (21), 265 (sh, 16), 293 (24). MS (70 eV) m/z (rel int) 345
(56, M+), 344 (100, M - 1). Anal. Calcd for C24H27NO: C,
83.43; H, 7.88; N, 4.06. Found: C, 83.35; H, 7.97; N, 3.97.
5-Ben zyliden e-9-bu tyl-3-[(N,N-dim eth ylam in o)m eth yl]-
2,3,5,6,7,8-h exa h yd r oa cr id in -4(1H )-on e H yd r och lor id e
(27‚HCl). A mixture of 3.0 g (0.87 mmol) of ketone 23, 1.24 g
(13.3 mmol) of N,N-dimethyl(methylene)ammonium chloride
(Aldrich), and 56 mL of acetonitrile was stirred under N2 at
room temperature for 24 h. The resulting precipitate was
collected by vacuum filtration and washed with ethyl acetate
(2 × 25 mL), yielding 3.77 g (95%) of Mannich salt 27‚HCl as
a white solid. Slow evaporation of a solution in CH2Cl2/ethyl
acetate gave a sample which was dried in vacuo for 18 h at
room temperature, mp 156-157 °C. 1H NMR (300 MHz,
CDCl3) δ 7.90 (s, 1 H), 7.3-7.4 (m, 4 H), 7.17 (t, J ) 6.3, 1 H),
3.81 (dd, J ) 5, 13 Hz, 1 H), 3.27 (dd, J ) 5, 10 Hz, 1 H),
3.03-3.13 (m, 3 H), 2.87 (s, 6 H), 2.52-2.63 (m, 4 H), 1.94 (m,
2 H), 1.77 (m, 2 H), 1.36 (m, 4 H), 0.90 (t, J ) 6 Hz, 3 H). 13C
NMR (75 MHz, CDCl3) δ 195.8, 152.2, 149.0, 144.3, 137.3,
136.5, 135.3, 135.1, 129.3, 128.1, 127.8, 126.6, 57.7, 44.8, 44.4,
30.1, 28.0, 27.9, 27.1, 26.4, 24.9, 23.0, 22.1, 14.0. IR (KBr)
3430 (s), 3018 (w), 2941 (s), 2692 (m), 1695 (s), 1388 (s), 1149
(m), 1090 (m), 764 (m), 955 (s).
5-Ben zyliden e-9-bu tyl-3-[(N,N-dim eth ylam in o)m eth yl]-
2,3,5,6,7,8-h exa h yd r oa cr id in -4(1H)-on e (27). A mixture of
0.13 g (0.29 mmol) of 27‚HCl, 30 mL of CH2Cl2, and 40 mL of
1 M aqueous NaOH solution was stirred vigorously for 1 h.
The layers were separated, and the aqueous layer was
extracted with CH2Cl2 (2 × 15 mL). The combined organic
solutions were dried (MgSO4) and filtered, and the filtrate was
concentrated to dryness in vacuo at room temperature. Re-
sidual solvent was removed at 0.5 mmHg, yielding 0.12 g
(100%) of Mannich base 27 as a colorless solid, mp 99-100
°C. 1H NMR (300 MHz, CDCl3) δ 8.09 (s, 1 H), 7.20-7.43 (m,
5 H), 3.07 (m, 1 H), 2.93 (m, 1 H), 2.86 (m, 4 H), 2.80 (m, 1 H),
2.78 (m, 2 H), 2.65 (t, J ) 6 Hz, 2 H), 2.44 (m, 1 H), 2.28 (s, 6
H), 1.96 (m, 1 H), 1.84 (m, 2 H), 1.46 (m, 4 H), 0.98 (t, J ) 6
Hz, 3 H). 13C NMR (CDCl3, 75 MHz) δ 198.3, 152.1, 148.7,
145.6, 137.9, 136.1, 135.3, 134.4, 129.6, 128.3, 127.9, 126.5,
58.6, 46.3, 45.7, 30.5, 28.0, 27.4, 26.6, 25.9, 24.2, 23.2, 22.5,
13.7. IR (KBr) 3401 (w), 3048 (w), 3001 (w), 2931 (s), 2919
(s), 2801 (s), 2757 (s), 1698 (s), 1554 (m), 1460 (m), 1437 (m),
1378 (m) 1261 (m), 1150 (m), 1031 (m), 716 (m), 690 (m). Anal.
Calcd for C27H34N2O: C, 80.55; H, 8.51. Found: C, 80.35; H,
8.46.
5-Ben zylid en e-9-bu tyl-1,2,3,4,5,6,7,8-octa h yd r oa cr id in -
4-ol Hyd r obr om id e (22‚HBr ). To a 1-L flask equipped with
a magnetic stirring bar, reflux condenser, and a 500 mL
addition funnel were added 38.9 g (0.15 mol) of 9-butyl-
1,2,3,4,5,6,7,8-octahydroacridine N-oxide (11) and 300 mL of
acetic anhydride. The apparatus was flushed with nitrogen,
and the reaction mixture was heated by means of a 110 °C oil
bath for 1 h. Benzaldehyde (100 mL, 104 g, 1 mol) was added
in one portion, and the resulting solution was heated at reflux
for 14 h (prolonged heating causes formation of a side-product).
The condenser was replaced with a simple distillation ap-
paratus, and the mixture was concentrated by vacuum distil-
lation at 2-35 mm pressure (the still head temperature should
not exceed 45 °C at 5 mmHg), collecting 330-340 mL of
distillate in
a receiving flask cooled by dry ice/acetone.
Methanol (300 mL) and concentrated hydrobromic acid (100
mL, 48% aqueous) were added to the brown residue, and the
resulting solution was heated under reflux for 4-6 h. The
reaction mixture was allowed to cool to room temperature, 300
mL of water was added, and most of the methanol was
removed by rotary evaporation. The resulting aqueous mix-
ture was extracted with CH2Cl2 (2 × 200 mL). The combined
extracts were dried (Na2SO4) and concentrated by rotary
evaporation. The resulting dark oil was triturated with 200
mL of acetone to yield 22‚HBr in two crops as a bright yellow
solid (40 g, 62%), mp 180-182 °C. 1H NMR (300 MHz, CDCl3)
δ 8.52 (s, 1 H), 7.36-7.62 (m, 5 H), 6.29 (d, J ) 5 Hz, 1 H),
5.56 (m, 1 H), 2.71-2.95 (m, 8 H), 1.92-2.18 (m, 6 H), 1.46-
1.49 (m, 4 H), 1.01 (t, J ) 7 Hz, 3 H). IR (KBr) 3440 (m),
3257 (s), 2952 (m), 2867 (s), 1613 (s), 1584 (m), 1505 (w), 1436
(w), 1412 (w), 1354 (m), 1329 (m), 1259 (w) 1198 (m), 767 (m),
698 (m). 13C NMR (75 MHz, CDCl3) δ 159.4, 151.5, 146.0,
135.9, 135.1, 133.3, 132.3, 130.2, 128.5, 128.2, 126.7, 63.4, 29.6,
29.3, 29.1, 26.4, 25.4, 25.3, 23.1, 21.6, 18.6, 13.5.
5-Ben zylid en e-9-bu tyl-1,2,3,4,5,6,7,8-octa h yd r oa cr id in -
4-ol (22). A solution of 40 g (9.3 mmol) of 22‚HBr in 200 mL
of CH2Cl2 was stirred vigorously with 200 mL of 1 M aqueous
NaOH for 1 h. The organic phase was dried (MgSO4) and
concentrated by rotary evaporation. The resulting pale yellow
oil was triturated with hexanes to yield 29.8 g (93%) of alcohol
22 as a pale yellow solid, mp 94-95 °C. 1H NMR (300 MHz,
CDCl3) δ 7.94 (s, 1 H), 7.35-7.43 (m, 4 H), 7.31 (t, J ) 6 Hz,
1 H), 4.66 (dd, J ) 5, 9 Hz, 1 H), 4.59 (s, 1 H), 2.74-2.89 (m,
6 H), 2.55 (m, 2 H), 2.35 (m, 1 H), 2.06 (m, 1 H), 1.80-1.87
(m, 4 H), 1.43 (m, 4 H), 0.98 (t, J ) 6 Hz, 3 H). 13C NMR (75
MHz, CDCl3) δ 154.8, 148.9, 148.6, 137.8, 135.6, 129.4, 129.2,
127.8, 127.5, 126.3, 125.9, 69.3, 30.22, 27.9, 25.8, 25.5, 23.1,
22.8, 19.5, 13.6. IR (KBr) 3412 (m), 2931 (s), 2848 (s), 1590
(w), 1554 (s), 1384 (s), 1090 (s), 1061 (s), 749 (m), 690 (s). Anal.
Calcd for C24H29NO: C, 82.95; H, 8.41; N, 4.03. Found: C,
82.79; H, 8.45; N, 3.80.
5-Ben zylid en e-9-b u t yl-2,3,5,6,7,8-h exa h yd r oa cr id in -
4(1H)-on e (23). A mixture of 95 g (0.27 mol) of alcohol 22
and 560 mL of DMSO was stirred at 40-45 °C under N2 until
the solid dissolved. The solution was cooled to room temper-
ature, acetic anhydride (400 mL) was added, and stirring was
continued at room temperature for 16 h. The reaction mixture
was transferred to a 4 L Erlenmeyer flask and diluted with
water (3 L) using an ice bath to minimize heating. The
resulting mixture was stirred at room temperature for 7 h and
then filtered. The residue was washed with water (2 × 150
mL) and dried in air. A solution of the crude product in 300
mL of CHCl3 was washed with 2% aqueous Na2CO3 solution
(2 × 150 mL) and then with 150 mL of water and dried
(MgSO4). Filtration and rotary evaporation gave a residue,
which was dissolved in hot ethyl acetate (450 mL). Hexane
(200 mL portions) was added to the boiling ethyl acetate
5-Ben zylid en e-9-bu tyl-3-m eth ylen e-2,3,5,6,7,8-h exa h y-
d r oa cr id in -4(1H)-on e (29). A mixture of 4.34 g (11 mmol)
of Mannich base 27 and 24 mL (55 g, 0.39 mol) of CH3I was
stirred at room temperature for 30 min, and then excess CH3I
was removed by rotary evaporation. The resulting pale yellow
solid (quaternary ammonium salt 28) was dissolved in 220 mL
of CH2Cl2. The solution was stirred at room temperature as
10 mL (7.3 g, 72 mmol) of triethylamine was added in one
portion. The solution became cloudy within a few minutes due
to the precipitation of triethylammonium iodide. After 10 min
the reaction mixture was shaken with 100 mL of H2O, and
the organic layer was separated, dried (Na2SO4), and concen-
trated by rotary evaporation. The residual off-white solid was

Heptacyclic Terpyridyl Molecular Clefts
J . Org. Chem., Vol. 63, No. 7, 1998 2241
dried in vacuo for 12 h, yielding 3.78 g (96%) of enone 29, mp
110-111 °C. 1H NMR (300 MHz, CDCl3) δ 8.14 (s, 1 H), 7.33-
7.44 (m, 4 H), 7.24 (t, J ) 6 Hz, 1 H), 6.28 (s, 1 H), 5.48 (s, 1
H), 3.00 (t, J ) 6 Hz, 2 H), 2.88 (m, 6 H), 2.67 (m, 2 H), 1.86
(m, 2 H), 1.46 (m, 4 H), 0.99 (t, J ) 7 Hz, 3 H). 13C NMR (75
MHz, CDCl3) δ 186.5, 152.8, 148.3, 146.5, 143.4, 138.1, 136.4,
135.3, 134.5, 129.7, 128.7, 128.0, 126.6, 121.5, 30.9, 30.8, 28.1,
27.5, 26.9, 25.3, 23.1, 22.6, 13.7.
completely dissolved (5-10 m). 5-Benzylidene-9-butyl-3-[(N,N-
dimethylamino)methyl]-2,3,5,6,7,8-hexaydroacridin-4(1H)-
one HCl salt (27‚HCl, 7.91 g, 18 mmol) was added to the
solution, and heating was continued at 80 °C. The Mannich
salt dissolved, and a precipitate formed within several min-
utes. The reaction mixture was heated briefly to 110 °C, and
then it was allowed to cool to room temperature. The
precipitate was collected by vacuum filtration, washed with
ethyl acetate, and dried in vacuo, yielding 8.26 g (67%) of crude
26. The crude product was dissolved in 40 mL of CH2Cl2 and
precipitated by addition of 300 mL of ethyl acetate. The
precipitate was collected by filtration and dried in vacuo,
yielding 7.22 g (59%) of pure 26. 1H NMR (300 MHz, CDCl3)
δ 8.30 (s, 2 H), 7.41 (s, 1 H), 7.24 (m, 4 H), 7.11 (m, 6 H), 2.94
(s, 8 H), 2.78-2.86 (m, 8 H), 2.67 (t, J ) 6 Hz, 4 H), 1.83 (quin,
J ) 6 Hz, 4 H), 1.45 (m, 8 H), 0.97 (t, J ) 6 Hz, 6 H). 13C
NMR (75 MHz, CDCl3) δ 152.0, 151.6, 149.5, 146.6, 138.7,
140.0, 134.3, 133.4, 130.6, 130.5, 129.7, 127.6, 125.8, 31.1, 28.2,
27.9, 27.6, 26.7, 24.0, 23.1, 23.0, 13.9. IR (KBr) 3070 (w), 3030
(w), 2950 (s), 2860 (m), 1600 (w), 1550 (m), 1440 (s), 1380 (s),
1240 (m), 1180 (m). Anal. Calcd for C49H51N3: C, 86.30; H,
7.54; N, 6.16. Found: C, 86.04; H, 7.56; N, 5.86.
1,11-D ib e n zy lid e n e -5,15-d ib u t y l-1,2,3,4,6,7,11,12,
13,14,16,17-d od eca h yd r oa cr id in o[3,4-c]b en zo[j][1,10]-
p h en a n th r olin e (33). Ketone 23 (0.10 g, 0.29 mmol) was
converted to 26 by method C, as described above. After
collection of the precipitate from the reaction mixture, the
filtrate was concentrated by rotary evaporation and chromato-
graphed (neutral alumina, hexanes/EtOAc, 1:1 (v/v)), yielding
0.01 g (4%) of 33 as a yellow oil. 1H NMR (300 MHz, CDCl3)
δ 8.64 (s, 1 H), 8.21 (s, 1 H), 8.04 (s, 1 H), 7.21-7.45 (m, 10
H), 3.79 (t, J ) 6 Hz, 2 H), 2.88-2.92 (m, 14 H), 2.70-2.72
(m, 4 H), 1.84-1.97 (m, 4 H), 1.47-1.49 (m, 8 H), 0.96-1.00
(m, 6 H). 13C NMR (75 MHz, CDCl3) δ 152.8, 151.2, 149.6,
149.1, 149.0, 148.8, 148.4, 139.6, 138.7, 138.2, 136.2, 133.3,
131.8, 131.6, 130.8, 130.5, 130.3, 129.6, 129.4, 129.4, 128.1,
127.8, 127.6, 126.8, 126.4, 125.0, 125.0, 31.4, 31.2, 31.1, 28.1,
27.9, 27.5, 26.4, 26.2, 26.0, 24.4, 24.2, 23.0, 22.9, 22.6, 22.3,
13.9, 13.8. IR (KBr) 3050 (w), 2954 (s), 1550 (m), 1491 (m),
1443 (m), 1390 (m), 1290 (m), 908 (m), 729 (m), 697 (m), 641
(m). Anal. Calcd for C49H51N3: C, 86.30; H, 7.54; N, 6.16.
Found: C, 86.21; H, 7.75; N, 5.92.
3,4-(5-Ben zylid en e-9-b u t yl-1,2,5,6,7,8-h exa h yd r oa cr i-
d in o[4,3-c])-8,9-(8-b en zylid en e-4-b u t yl-5,6,7,8-t et r a h yd -
r oqu in o[8,9-f])-2-oxa sp ir o[5.5]u n d eca -3,8-d ien -7-on e (31).
The chromatogram used to isolate side product 33 described
above also yielded spiro-dimer 31 as a pale yellow solid (ca.
4% of the crude product by 1NMR spectroscopy). 1H NMR (300
MHz, CDCl3) δ 8.06 (s, 1 H), 7.71 (s, 1 H), 7.2-7.4 (m, 10 H),
3.55 (m, 1 H), 2.0-3.0 (m, 23 H), 1.80 (m, 4 H), 1.31-1.41 (m,
8 H), 0.94 (m, 6 H). 13C NMR (75 MHz, CDCl3) δ 194.2, 152.1,
148.7, 148.2, 146.5, 146.0, 145.0, 143.2, 138.7, 138.0, 136.6,
136.0, 135.4, 134.3, 129.6, 129.3, 128.7, 128.0, 127.9, 127.7,
127.7, 126.4, 125.9, 125.4, 111.7, 76.3, 33.4, 31.06, 29.9, 27.8,
27.9, 27.8, 27.3, 27.3, 26.7, 26.2, 26.1, 23.5, 23.1, 23.0, 22.9,
22.9, 22.4, 21.6, 13.7, 13.5. Anal. Calcd for C50H54N2O2: C,
83.99; H, 7.61; N, 3.92. Found: C, 83.65; H, 7.59; N, 3.89.
5,11-Dib u t yl-2,3,4,6,7,9,10,12,13,14-d eca h yd r oa cr id i-
n o[4,3-b]b en zo[j][1,10]p h en a n t h r olin e-1,15-d ion e (6).
Meth od A. An ozone/oxygen mixture was bubbled through a
-70 °C solution of 7.0 g (10.3 mmol) of dibenzylidene terpyridyl
derivative 26 in 200 mL of dichloromethane/methanol (3:1,
v/v). During the first 10 min, the color of the solution changed
from brown to light yellow and then to yellow-green at the
end of the reaction period (50 min). Nitrogen was bubbled
through the cold solution for 10 min, and then 6 mL of
dimethyl sulfide was added. The resulting mixture was
allowed to warm to room-temperature overnight and then
1,15-Dib e n zylid e n e -5,11-d ib u t yl-1,2,3,4,6,7,9,10,12,
13,14,15-d o d e c a h y d r o a c r id in o [4,3-b ]b e n zo [j][1,10]-
p h en a n th r olin e (26). Meth od A. A solution of 14.6 g (42.3
mmol) of ketone 23, 30 mL (0.39 mol) of 1,1-dimethylhydrazine,
30 mL of ethanol, and 90 mL of cyclohexane was heated under
reflux for 1 h with the reflux solvent passing through a Soxhlet
extractor containing 3A molecular sieves. The solvents were
evaporated in vacuo, and the residual viscous brown oil was
dissolved in 50 mL of benzene. Rotary evaporation was
repeated to remove remaining water and 1,1-dimethylhydra-
zine. A solution of the residue in CH2Cl2 was filtered through
Woelm neutral alumina (150 g, activity II), washing with 200
mL of CH2Cl2. To the resulting yellow solution of hydrazone
24 was added 6.15 g (41.6 mmol) of trimethyloxonium tet-
rafluoroborate, and the resulting mixture was stirred at room
temperature for 40 min. The resulting dark orange solution
of salt 25 in CH2Cl2 was added over a period of 90 min to a
Pyrex glass tube inclined at an angle of 30° and heated at 235-
240 °C along a path length of 31 cm by means of a tube
furnace, while N2 gas was flowing through the tube at a rate
of approximately 1 L/min. The viscous product mixture
collected at the exit of the tube was dissolved in 60 mL of
CHCl3. This solution was washed with 1 M aqueous NaOH
(100 mL), dried (Na2SO4), and concentrated in vacuo to a dark
brown glass. This residue was dissolved in 100 mL of ethyl
acetate. After standing for 24 h, this solution deposited a
precipitate, which was collected by vacuum filtration and
washed thoroughly with ethyl acetate. This first crop was
dried in air to give 2.45 g of 26 as a pale yellow powder, which
was pure according to its 1H NMR spectrum. The mother
liquor was evaporated to dryness. A mixture of the residue
with 20 g (0.29 mol) of hydroxylamine hydrochloride and 200
mL of ethanol was heated at reflux under N2 for 5.5 h. The
ethanol solution was decanted from excess hydroxylamine
hydrochloride, which crystallized when the reaction mixture
was cooled. The supernatant was diluted with 500 mL of 1 M
aqueous HCl, and the resulting solution was extracted with
CHCl3 (2 × 75 mL). The combined extracts were washed with
1 M aqueous NaOH (100 mL), dried (MgSO4), filtered, and
evaporated. A solution of the resulting dark brown glass in
ethyl acetate (100 mL) was allowed to stand for 24 h, and a
second crop of 26 (2.40 g) was collected, washed with ethyl
acetate, and dried in air. The combined yield was 4.85 g (33%)
of relatively pure material that could be converted directly to
diketone 6. An analytical sample was obtained by recrystal-
lization from benzene and dried in vacuo for 12 h at room
temperature, mp 256-258 °C.
Meth od B. A mixture of 0.10 g (0.29 mmol) of ketone 23,
0.03 g (0.39 mmol) of ammonium acetate, and DMSO (6 mL)
was heated at 85 °C for 5 min. A solution of 0.12 g (0.29 mmol)
of 5-benzylidene-9-butyl-3-[(N,N-dimethylamino)methyl]-2,3,5,
6,7,8-hexahydroacridin-4(1H)-one (27) in 4 mL of pyridine was
added to the preheated reaction mixture, and heating was
continued at 85 °C for an additional 1 h. The reaction mixture
was allowed to cool to room temperature, diluted with CH2Cl2
(30 mL), and extracted with 1 M aqueous NaOH (4 × 30 mL),
followed by water (30 mL). The aqueous solutions were
combined and washed with CH2Cl2 (20 mL). The combined
organic layers were dried (MgSO4), filtered, and concentrated
in vacuo. The resulting brownish yellow glass was triturated
with ethyl acetate (15 mL), yielding 0.14 g (70%) of 26 as a
pale yellow solid.
concentrated to minimum volume in vacuo at ca. 30 °C.
A
solution of the residue in 10 mL of CH2Cl2 was added dropwise
to 400 mL of ether with rapid stirring. The resulting precipi-
tate was collected by vacuum filtration, washed with ether (40
mL), and dried at 90 °C for 2 h to yield 4.45 g (81%) of 6 as a
beige solid. A second crop (0.66 g, 12%) was obtained by slow
evaporation of the mother liquor. A sample for microanalysis
Meth od C. To a three-necked round-bottomed flask fitted
with a magnetic stirrer, thermometer, and a condenser with
a nitrogen inlet tube were added 6.22 g (18 mmol) of ketone
23, 2.08 g (27 mmol) of ammonium acetate, and 175 mL of
DMSO. The mixture was heated at 80 °C until all solids

2242 J . Org. Chem., Vol. 63, No. 7, 1998
Bell et al.
was recrystallized from freshly distilled n-butyronitrile, washed
with acetone, and dried in vacuo at 60 °C for 12 h, mp 270-
275 °C dec. 1H NMR (300 MHz, CDCl3) δ 7.42 (s, 1 H), 4.46
(s, 2 H), 2.95-3.03 (m, 12 H), 2.76 (m, 8 H), 2.19 (m, 4 H),
1.47 (m, 8 H), 0.98 (t, J ) 7 Hz, 6 H). IR (KBr) 3400 (b), 2950
(s), 2860 (s), 1695 (s), 1650 (sh), 1560 (s), 1540 (sh), 1450 (sh),
1430 (s), 1410 (sh), 1380 (s), 1340 (sh), 1330 (m), 1270 (sh),
1220 (s), 1180 (s), 1130 (sh), 1100 (w), 1030 (m), 980 (w), 940
(w), 890 (w). UV-Vis (CH3CN, ꢀ × 10-3) λmax 237 (55.3), 310
(18.4), 344 (18.0). Anal. Calcd for C35H39N3O2‚2H2O: C, 73.78;
H, 7.61; N, 7.38. Found: C, 73.92; H, 7.61; N, 7.44.
2.28 (m, 4 H), 1.45-1.60 (m, 8 H), 1.03 (t, J ) 7 Hz, 6 H). IR
(KBr) 3090 (w), 3070 (w), 3020 (w), 2940 (s), 2920 (sh), 2860
(s), 2840 (sh), 1690 (s), 1625 (s), 1600 (sh), 1555 (s), 1480 (m),
1450 (w), 1425 (m), 1400 (w), 1390 (w), 1350 (s), 1325 (s), 1295
(s), 1280 (s), 1250 (s), 1230 (sh), 1175 (m), 1150 (m), 1065 (m),
930 (m), 915 (m), 890 (m), 780 (s), 740 (m), 720 (m), 710 (m),
700 (m), 680 (m), 540 (m). Anal. Calcd for C41H41N6O9Na: C,
62.75; H, 5.27; N, 10.71. Found: C, 62.47; H, 5.35; N, 10.69.
6‚K(p icr a te). A solution of 52 mg (0.092 mmol) of diketone
6 in 3 mL of CHCl3 was washed with 15 mL of an aqueous
solution containing 40 mg (0.15 mmol) of potassium picrate
and 42 mg (0.30 mmol) of K2CO3. The CHCl3 solution was
concentrated to dryness in vacuo, and the crude product was
recrystallized from benzene/95% ethanol (2:1, v/v). The result-
ing fine, yellow needles were washed with benzene and dried
in vacuo at room temperature for 12 h, yielding 59 mg (77%)
of 6‚K(picrate), mp 189-190 °C. The 0.33 equiv of benzene
contained in the crystals could not be removed by further
drying at room temperature. 1H NMR (300 MHz CDCl3) δ 8.46
(s, 2 H), 7.44 (s, 1 H), 7.36 (s, 2 H), 2.9-3.1 (m, 12 H), 2.82 (t,
J ) 6 Hz, 4 H), 2.73 (m, 4 H), 2.25 (m, 4 H), 1.45-1.60 (m, 8
H), 1.02 (t, J ) 7 Hz, 6 H). IR (KBr) 3080 (w), 3020 (w), 2940
(s), 2920 (s), 2860 (s), 1690 (s), 1630 (s), 1600 (m), 1550 (s),
1505 (m), 1485 (m), 1470 (m), 1450 (w), 1430 (m), 1420 (sh),
1405 (w), 1350 (m), 1320 (s), 1290 (m), 1250 (s), 1225 (m), 1210
(sh), 1180 (sh), 1170 (m), 1150 (m), 1135 (sh), 1060 (m), 900
(m), 890 (sh), 785 (m), 740 (m), 700 (m), 665 (m). Anal. Calcd
Meth od B. A solution of 0.57 g (1.1 mmol) of heptacyclic
terpyridyl 20, 1.11 g (7.3 mmol) of 85% m-chloroperoxybenzoic
acid, and 11 mL of CH2Cl2 was stirred at room temperature
for 75 min. The reaction mixture was washed with 1 M
aqueous NaOH (2 × 40 mL), dried (MgSO4), and concentrated
in vacuo, yielding crude di-N-oxide 34 as a light brown glass.
(Note: incomplete removal of MCPBA at this stage could lead
to the formation of potentially exp losive diacetyl peroxide in
the next step.) A solution of this intermediate, 5 mL of acetic
anhydride, and 0.16 mL of acetyl chloride was stirred for 15
min at room temperature, 0.30 g (3.7 mmol) of sodium acetate
was added, and the resulting mixture was stirred at 100 °C
for 1 h. Most of the acetic anhydride was removed from the
cooled reaction mixture by rotary evaporation. A solution of
the residue in 5 mL of CH2Cl2 was shaken with 25 mL of 2 M
aqueous NaOH, saturated aqueous NaCl was added, the layers
were separated, and the organic layer was dried (MgSO4).
Evaporation gave a brown solid, which was chromatographed
using 70 g of neutral alumina (Act. II), eluting with CH2Cl2/
acetone (3:2, v/v). Thus 0.44 g (66%) of 5,11-dibutyl-1,2,3,
4,6,7,9,10,12,13,14,15-dodecahydroacridino[4,3-b]benzo[j]-
[1,10]phenanthroline-1,15-diol diacetate was obtained as a
light tan powder (mixture of diastereomers). 1H NMR (300
MHz, CDCl3) δ 7.40 (s, 1 H), 6.03 (m, 2 H), 2.85-3.00 (m, 8
H), 2.60-2.75 (m, 8 H), 2.18 (s, 3 H), 2.17 (s, 3 H), 1.85-2.30
(m, 8 H), 1.40-1.55 (m, 8 H), 0.98 (m, 6 H). A solution of 0.44
g (0.70 mmol) of this intermediate and 9 mL of 2 M aqueous
HCl was heated under reflux for 85 min. The resulting orange
solution was cooled to room temperature, made basic with 20
mL of 2 M aqueous NaOH and extracted with CHCl3 (3 × 7
mL). The combined extracts were dried (MgSO4) and concen-
trated in vacuo. The residue was washed with benzene and
dried in air, yielding 0.27 g (72%) of 5,11-dibutyl-1,2,3,4,6,
7,9,10,12,13,14,15-dodeca h ydr oa cr idin o[4,3-b]ben zo[j]-
[1,10]phenanthroline-1,15-diol (35) as a tan powder (mixture
of diastereomers). 1H NMR (300 MHz, CDCl3) δ 7.41 (s, 1 H),
4.95-5.0 (m, 2 H), 3.8 (bs, 2 H), 2.95 (m, 8 H), 2.5-3.0 (m, 8
for
C41H41N6O9K‚1/3C6H6: C, 62.46; H, 5.24; N, 10.16.
Found: C, 62.57; H, 5.34; N, 9.95.
(6)2Ca (CF 3SO3)2. Dibenzylidene derivative 26 (4.9 g, 7.1
mmol) was ozonized according to method A for preparation of
diketone 6. After the solvents were removed in vacuo at ca.
30 °C, the residue was dissolved in ether and the resulting
solution was allowed to stand for several hours at room
temperature. Fine white needles of diketone 6 (1.37 g, 34%)
were collected by filtration and washed with acetone. The
combined filtrates were extracted with 1 M aqueous HCl (2 ×
50 mL). The combined aqueous layers were made basic with
2 M aqueous LiOH and extracted with CHCl3 (50 mL). The
CHCl3 extract was washed with H2O (100 mL) and concen-
trated by rotary evaporation. A solution of resulting glassy
residue, 1 g (3.0 mmol) of calcium trifluoromethanesulfonate
and ca. 5 mL of acetone was evaporated to dryness, and then
the residue was chromatographed using 100 g of neutral
alumina (Act. II), eluting with CH2Cl2/2-propanol/triethy-
lamine (44:5:1, v/v/v). The resulting greenish-brown product
was dissolved in 15 mL of CH2Cl2, and 45 mL of ethyl acetate
was added. After several hours the crystallized product was
filtered, washed with ethyl acetate/CH2Cl2 (3:1, v/v), and dried
in air to yield 1.66 g (33%) of complex (6)2Ca(OTf)2 as pale
yellow-green plates, mp 275-285 °C dec. An analytical sample
was obtained by adding ethyl acetate to a solution of the
product in CH2Cl2, drying for 4 h at room temperature in
vacuo, yielding pale yellow plates, mp 275-285 °C dec. 1H
NMR (300 MHz, CDCl3) δ 7.80 (s, 1 H), 3.26 (s, 8 H), 2.80-
2.95 (m, 8 H), 2.13 (t, J ) 6 Hz, 4 H), 1.72 (m, 4 H), 1.4-1.6
(m, 8 H), 1.01 (t, J ) 7 Hz, 6 H). 13C NMR (75 MHz, CDCl3)
δ 199.7, 152.3, 150.0, 147.6, 144.2, 140.5, 137.3, 136.9, 135.8,
37.3, 31.0, 28.3, 26.1, 25.1, 24.0, 23.0, 21.9, 13.8. IR (KBr)
3500 (w, br), 2950 (s), 2870 (s), 1740 (m), 1680 (s), 1570 (s),
1460 (sh), 1440 (s), 1360 (sh), 1260 (s, br), 1180 (m), 1140 (s),
1020 (s), 1000 (sh), 900 (w), 720 (w). Anal. Calcd for
H), 1.7-2.2 (m, 8 H), 1.45-1.5 (m, 8 H), 0.97 (m, 6 H).
A
solution of 0.25 g (0.47 mmol) of this intermediate, 0.42 mL of
a 1.1 M solution of H2SO4 in CH3CN, and 5 mL of CH3CN was
stirred as 0.51 g (1.2 mmol) of Dess-Martin periodinane
(Ca u tion : explosion hazard)32 was added in one portion. The
resulting suspension was stirred at room temperature for 10
min, resulting in a cloudy yellow solution, which was diluted
with 10 mL of 1 M aqueous NaHCO3 and 10 mL of 1 M
aqueous Na2S2O3. The resulting mixture was extracted with
CHCl3 (2 × 7 mL), and the combined extracts were dried
(MgSO4) and evaporated in vacuo. The brown, glassy residue
was dissolved in 1.5 mL of acetone. The product crystallized
from this solution at room temperature; it was collected by
filtration and washed with acetone. A small second crop was
collected from the mother liquor, yielding a total of 197 mg
(74%) of diketone 6 as a greenish-brown solid, mp 180-190
C
36H39N3O5SF3Ca0.5: C, 61.52; H, 5.59; N, 5.98. Found: C,
61.49; H, 5.54; N, 5.91.
1
°C dec. According to its H NMR spectrum, this product was
2,6-Bis[3-(d im eth yla m in o)p r op en oyl]p yr id in e (36). A
mixture of 1.5 g (9.2 mmol) of 2,6-diacetylpyridine and 10 mL
of tert-butoxybis(dimethylamino)methane was heated under
N2 at 85 °C for 15 min and then cooled to room temperature.
Ether (10 mL) was added, and the resulting yellow-orange
solid was collected by vacuum filtration, washed with cold
ether (2 × 15 mL), and dried in vacuo to afford 2.2 g (89%) of
36 as a pale yellow solid, mp 232-233 °C (lit.45 222-230 °C).
1H NMR (300 MHz, CDCl3) δ 8.22 (d, J ) 7.5 Hz, 2 H), 7.92
(d, J ) 12 Hz, 2 H), 7.89 (t, J ) 7.5 Hz, 1 H), 6.61 (d, J ) 12
Hz, 2 H), 3.18 (s, 6 H), 2.99 (s, 6 H). 13C NMR (75 MHz, CDCl3)
less pure than that obtained by method A.
6‚Na (p icr a te). A solution of 53 mg (0.092 mmol) of
diketone 6 in 3 mL of CHCl3 was washed with 11 mL of an
aqueous solution containing 45 mg (0.18 mmol) of sodium
picrate and 65 mg (0.78 mmol) of Na2CO3. The CHCl3 solution
was concentrated to dryness in vacuo, and the crude product
was recrystallized from 95% ethanol and dried in vacuo,
yielding 58 mg (80%) of 6‚Na(picrate) as a yellow powder, mp
165-165 °C. 1H NMR (300 MHz, CDCl3) δ 8.41 (s, 2 H), 7.43
(s, 1 H), 3.0-3.15 (m, 12 H), 2.8-2.9 (m, 4 H), 2.75 (m, 4 H),

Heptacyclic Terpyridyl Molecular Clefts
J . Org. Chem., Vol. 63, No. 7, 1998 2243
δ 186.5, 154.4, 149.2, 137.2, 123.4, 91.2, 44.9, 36.9. MS (FAB)
m/z (rel int) 273 (100, M+).
Sta bility Con sta n ts of Alk a li Meta l P icr a te Com -
p lexes. The H2O/CHCl3 extraction experiments were carried
out at 21-24 °C exactly as described previously.46 Stability
constants were calculated with absorbances measured for both
phases in the case of host 6 and for the aqueous phase only in
the case of host 20. Values given in Table 1 are averages of
several determinations and errors were estimated to be (0.2-
0.4 log Ks units.
2,6-Bis(5,6,7,8-tetr a h yd r oqu in ol-2-yl)p yr id in e (37). A
solution of 3.6 g (53 mmol) of potassium tert-butoxide, 70 mL
of THF and 2.0 mL (1.9 g, 19 mmol) of cyclohexanone was
stirred for 1 min at room temperature. Bis(enaminone) 36
(0.30 g, 1.1 mmol) was added in one portion, and the resulting
mixture was stirred for 10 h. The reaction mixture was
acidified with acetic acid (25 mL), and the THF was removed
by rotary evaporation. Ammonium acetate (0.80 g, 10.3 mmol)
was added, and the resulting mixture was heated at 110 °C
for 1 h. Volatile materials were removed in vacuo, and a
solution of the resulting residue in methylene chloride (40 mL)
was washed with water (3 × 50 mL). The organic layer was
concentrated to dryness by rotary evaporation, and a solution
of the oily residue in a few milliliters of CH2Cl2 was filtered
through neutral alumina, eluting with CH2Cl2/2-propanol (20:
1, v/v), to yield 0.16 g, 42% of terpyridine 37 as a yellow solid,
mp 89-90 °C. 1H NMR (300 MHz, CDCl3) 8.37 (d, J ) 8 Hz,
2 H), 8.31 (d, J ) 8 Hz, 2 H), 7.85 (t, J ) 8 Hz, 1 H), 7.49 (d,
J ) 8 Hz, 2 H), 3.01 (t, J ) 6 Hz, 4 H), 2.83 (t, J ) 6 Hz, 4 H),
1.79-1.98 (m, 8 H). 13C NMR (75 MHz, CDCl3) 156.6, 155.7,
153.6, 137.4, 137.3, 132.3, 120.2, 118.4, 32.8, 28.7, 23.2, 22.8.
MS (FAB) m/z (rel int) 341 (100, M+). Anal. Calcd for
Ack n ow led gm en t. This research was supported by
the National Institutes of Health (PHS Grant GM R01-
32937) and funds for purchase of the 600 MHz spec-
trometer were provided by NIH, NSF, Center for
Biotechnology, and SUNY Stony Brook. Professor D. L.
J ameson is thanked for providing details of his terpy-
ridine synthesis prior to publication.
Su p p or t in g In for m a t ion Ava ila b le: Proton NMR data
complete with peak assignments (3 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
C
23H23N3: C, 80.90; H, 6.79; N, 12.30. Found: C, 80.66; H,
6.71; N, 12.11.
J O9720041