Preparation of N-aryl azacrown ether derivatives, using arene-iron chemistry

Article abstract of DOI:10.1021/jo020527p

m- or p-phenylenediamine and m- or p-chlorophenyl-substituted azacrown ether derivatives were synthesized through sequential nucleophilic substitution of [(η⁵-cyclopentadienyl)(η⁶-(m- or p-dichlorobenzene))] iron hexafluorophosphate

Full text of DOI:10.1021/jo020527p

P r ep a r a tion of N-Ar yl Aza cr ow n Eth er Der iva tives, Usin g
Ar en e-Ir on Ch em istr y
Anthony J . Pearson* and Wenjing Xiao
Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106
ajp4@po.cwru.edu
Received August 9, 2002
m- or p-phenylenediamine and m- or p-chlorophenyl-substituted azacrown ether derivatives were
synthesized through sequential nucleophilic substitution of [(η5-cyclopentadienyl)(η6-(m- or p-
dichlorobenzene))]iron hexafluorophosphate by azacrown ethers and cyclohexaamines. Monoaryl-
ation is the main reaction for diazacrown ethers. The overall yield from the starting complex is
50-96% for multiple steps.
In tr od u ction
complexes in our laboratory.6 Ruthenium-arene com-
plexes are stable toward ambient light and air, and are
easy to handle, but the demetalation requires UV-light
and very low solution concentration. Iron-arene com-
plexes are much more sensitive toward light, which in
turn makes the demetalation relatively easy. Moreover
the cost of iron is much lower than that of ruthenium.
Construction of an arene-nitrogen bond is achievable
via several approaches. Traditional aromatic nucleophilic
substitution requires strong electron-withdrawing groups
on the phenyl ring. Ullmann-type coupling employs harsh
reaction conditions. The benzyne mechanism and the
S
RN1 mechanism only afford primary arylamines.1 The
Direct attachment of azacrown ethers to aromatic rings
has been attempted through all the above pathways.
Lapouyade et al. made substituted aryl crowns via SNAr
reaction and multistep transformation to the desired
functionality.7 High-pressure SNAr reaction was adopted
to prepare various aryl and heteroaryl crown ethers.8
Palladium-catalyzed amination has been used to generate
some simple aryl crowns.9
latter two procedures can tolerate very limited function-
ality on the phenyl ring.
Over the last two decades, transition-metal-catalyzed
amination of aryl halides or triflates has been developed
and well-studied by several groups.2,3 Palladium-cata-
lyzed cross-coupling is especially valuable because it
shows relatively high compatibility with functional groups
and provides medium to high yields depending on the
substrates. Starting with aryl polyhalides, symmetrical
aryl polyamines can be made.4
The transition-metal-mediated SNAr reaction opens
another door to the synthesis of arylamines. Various
transition metals have been used to form metal-arene
complexes.5 Complexation with the metal lowers the
electron density of the phenyl ring so that nucleophilic
attack can occur. The most attractive feature of this
method is that sequential nucleophilic substitutions can
proceed easily, leading to unsymmetrical phenylenedi-
amine or -triamine. Several p-phenylenediamine deriva-
tives have been made via iron- or ruthenium-arene
Previous studies in our laboratory showed that the
fluorescence and redox potential of crown-substituted
p-phenylenediamines respond to metal cations selec-
tively, which makes this type of molecule useful for
possible molecular devices.10 The synthesis was achieved
via arene-ruthenium complexes.11 Here we report more
convenient syntheses of m- or p-phenylenediamine and
m- or p-chlorophenyl-substituted azacrown ether deriva-
tives via arene-iron chemistry.
(6) (a) Pearson, A. J .; Gelormini, A. M.; Fox, M. A.; Watkins, d. J .
Org. Chem. 1996, 61, 1297-1305. (b) Pearson, A. J .; Gelormini, A. M.
Tetrahedron Lett. 1997, 38 (29), 5123-5126. (c) Pearson, A. J .; Hwang,
J .-J . J . Org. Chem. 2000, 65, 3466-3472.
(7) (a) Le´tard, J . F.; Lapouyade, R.; Rettig, W. Pure Appl. Chem.
1993, 65 (8), 1705-1712. (b) Crochet, P.; Malval, J .-P.; Lapouyade, R.
Chem. Commun. 2000, 289-290.
(8) (a) Matsumoto, K.; Hashmoto, M.; Toda, M.; Tsukube, H. J .
Chem. Soc., Perkin Trans. 1 1995, 2497-2502. (b) Ciobanu, M.;
Matsumoto, K. Liebigs Ann. 1997, 623-635.
(1) For examples of each of the described cases, see: March, J .
Advanced Organic Chemistry, 4th ed.; New York, 1992 and references
therein.
(2) Wolfe, J . P.; Wagsaw, S.; Marcoux, J .-F.; Buchwald, S. L. Acc.
Chem. Res. 1998, 31, 805-818.
(3) Hartwig, J . F. Angew. Chem., Int. Ed. 1998, 37, 2046-2067.
(4) (a) Witulski, B.; Senft, S.; Thum, A. Synlett, 1998, 504-506. (b)
Yamaoto, T.; Nishiyama, M.; Koie, Y. Tetrahedron Lett. 1998, 39,
2367-2370. (c) Hauck, S.; Lakshmi, K. V.; Hartwig, J . F. Org. Lett.
1999, 1 (13), 2057-2060. (d) Brenner, E.; Schneider, R.; Fort, Y.
Tetrahedron 1999, 55, 12829-12842. (e) Desmarets, C.; Schneider, R.;
Fort, Y. Tetrahedron Lett. 2000, 41, 2875-2879. (f) Zhang, X.-X.;
Sadighi, J . P.; Mackewitz, T. W.; Buchwald, S. L. J . Am. Chem. Soc.
2000, 122, 7606-7607.
(9) (a) Witulski, B.; Zimmerman Y.; Darcos, V.; Desvergne, J .-P.;
Bassani, D. M.; Bouas-Laurent, H. Tetrahedron Lett. 1998, 39, 4807-
4808. (b) Witulski, B. Synlett 1999, 8, 1223-1226. (c) Zhang, X.-X.;
Buchwald, S. L. J . Org. Chem. 2000, 65, 8027-8031.
(10) (a) Pearson, A. J .; Hwang, J .-J .; Ignatove, M. E. Tetrahedron
Lett. 2001, 42, 3537-3540. (b) Pearson, A. J .; Hwang, J .-J . Tetrahedron
Lett. 2001, 42, 3541-3543.
(11) Pearson, A. J .; Hwang, J .-J Tetrahedron Lett. 2001, 42, 3533-
3536.
(5) Astruc, D. Tetrahedron 1983, 39, 4027-4095.
10.1021/jo020527p CCC: $25.00 © 2003 American Chemical Society
Published on Web 02/20/2003
J . Org. Chem. 2003, 68, 2161-2166
2161

Pearson and Xiao
SCHEME 1
Resu lts a n d Discu ssion
F IGURE 1. 1H NMR patterns of phenyl and Cp protons at
different stages of substitution (in acetone-d6).
The major problem for preparation of the requisite
dichlorobenzene-iron complexes is low yield and deha-
logenation of starting material.12,13 The best yield previ-
ously recorded in our laboratory was around 25%.14
Careful investigation of reaction conditions in the present
study reveals that lower temperature at the beginning
improves the yield up to 35% based on added ferrocene
(actually excess ferrocence and dichlorobenzene can be
recovered after reaction workup). No dehalogenation of
dichlorobenzene was observed. Several precautions were
taken when carrying out the reaction. The procedure is
run under argon or nitrogen atmosphere; ferrocene was
sublimed immediately before use; AlCl3 and water were
added slowly. The reaction mixture was maintained at
55 °C for several hours after all reagents had been added.
During the reaction workup, water was added very slowly
to reduce possible damage by heat generated during the
hydrolysis of excess AlCl3. The reaction mixture becomes
viscous with time and therefore vigorous stirring is
needed.
Sequential amination of dichlorobenzene-iron complex
1 with secondary cyclic amines was examined, which
included monoazacrown ethers, diazacrown ethers, and
cyclohexaamines. Compared with cyclohexaamines, an
azacrown ether is a relatively weak nucleophile. There-
fore it was attached to the phenyl ring first. Then the
second chloride is substituted by a cyclohexaamine. The
two steps can be carried out in one pot. The reaction flask
should be covered with aluminum foil because this type
of iron-arene complex is sensitive even to room light.
Both the crown ether and amine are in excess, but the
crown ether can be recovered and reused. Different
solvents can be used for the reaction: THF, CH3CN, and
CH2Cl2 are useful. CH3CN is usually better for the second
step because some amines are more soluble in it. At room
temperature, the crown substitution requires around 5
to 9 days for completion, and the cyclohexaamine sub-
stitution requires around 2 to 4 days. At reflux temper-
ature, both steps can be completed in several hours to
overnight without compromising selectivity, and the
overall yield is also high.
Scheme 1 presents the general procedure for the
synthesis of the title compounds (the m-chlorophenyl
complex precursors to compounds 6 and 7 (Figure 2) are
not shown in the scheme).
Various demetalation procedures have been used in our
laboratory.6,14,15 During this work, we found that irradia-
tion with a 100-W Q-beam halogen lamp worked well for
(12) Nesmeyanov, A. N.; Vol’kenau, N. A.; Bolesova, I. N. Tetrahe-
dron Lett. 1963, 1725-1729.
(13) Khand, I. U.; Pauson, P. L.; Watts, W. E. J . Chem. Soc. C 1968,
2261-2265.
(14) Pearson, A. J .; Gelormini, A. M. J . Org. Chem. 1994, 59, 4561-
(15) Pearson, A. J .; Park, J . G.; Zhu, P. Y. J . Org. Chem. 1992, 57,
3583-3589.
4570.
2162 J . Org. Chem., Vol. 68, No. 6, 2003

Preparation of N-Aryl Azacrown Ether Derivatives
F IGURE 2. N-(m-/p-Chlorophenyl or m-/p-phenyldiamine)crown ethers (overall yield from dichlorobenzene iron complex).
all the metal complexes. The demetalation was carried
out in CH3CN, and the reaction solution was heated to
reflux by the irradiation. With good control, the overall
yield from the m- or p-dichlorobenzene iron complex was
50 to 96% depending on the amine substrates.
Figure 2 shows a selection of the products obtained
from the above procedure. All these compounds bear a
free amine or a hydroxyl group that can be further
manipulated, for example by attaching an electron ac-
ceptor moiety to form a donor-acceptor system. Com-
pound 4f has two open sites for further functionalization.
Compounds 4a -c were prepared from monoazacrown
ethers. Compounds 4d -f, 5a ,b, 6, and 7 were made from
diazacrown ethers. Compounds 6 and 7 were from the
m-dichlorobenzene iron complex, which is similar to the
p-dichlorobenzene iron complexes in these reactions.
Even though the crown ether is in excess amount, the
reaction stops at monosubstitution. Once one chloride is
substituted by the crown amine, the phenyl ring is less
electrophilic, so it is more difficult for a second crown to
attack. It is also noteworthy that selective monoarylation
of diazacrown ethers proceeds well. By controlling the
amount of crown ether and the reaction time, disubsti-
tution can be avoided. Most of the known diazacrown
ether derivatives are substituted symmetrically.16 For
diaza-15-crown-5 derivatives 4d and 5a there is no
symmetry axis across the two crown amines, which is
All the complexes are yellow to red-orange and oily,
and they are soluble in THF, CH3CN, CH3COCH3, and
CH2Cl2, but insoluble in ethyl ether, hexanes, and ethyl
acetate. Generally there is no need to rigorously purify
the metal complexes, thereby avoiding exposure of the
complex to room light and air. Complexes 2a , 2b, and
3b are stable enough to tolerate flash chromatography
on silica gel, but complexes containing a free secondary
amine are very polar, therefore difficult to elute from the
column. In most cases, washing the crude reaction
product with ethyl ether removes most excess crown
ether and amine. Purification of the final product was
done by flash chromatography on silica gel in the pres-
ence of Et3N.
1H NMR is very useful for monitoring the progress of
the sequential reactions. The four phenyl protons show
characteristic chemical shifts and splitting patterns at
different stages. The five Cp protons always appear as a
singlet but with different chemical shifts upon arene
(16) (a) Kulstad, S.; Malmsten, L. A° . Acta Chem. Scand. Ser. B 1979,
33, 469-474. (b) Gatto, V. J .; Gokel, G. W. J . Am. Chem. Soc. 1984,
106, 8240-8244. (c) Gatto, V. J .; Arnold, K. A.; Viscarello, A. M.; Miller,
S. R.; Morgan, C. R.; Gokel, G. W. J . Org. Chem. 1986, 51, 5373-
5384. (d) Tsukube, H.; Adachi, H.; Morosawa, S. J . Chem. Soc. Pekin
Trans. 1 1989, 89-93. (e) Fages, F.; Desvergne, J .-P.; Bouas-Laurent,
H.; Lehn, J .-M.; Konopelski, J . P.; Marsau, P.; Barrans, Y. J . Chem.
Soc., Chem. Commun. 1990, 655-658. (f) Bourson, J .; Pouget, J .;
Valeur, B. J . Phys. Chem. 1993, 97, 4552-4557. (g) Crossley, R.;
Goolamali, Z.; Gosper, J . J .; Sammes, P. G. J . Chem. Soc., Perkin Trans.
2 1994, 5113-520. (h) Katritzsky, A.; Belyakov, S.; Sorochinsky, A. E.
J . Org. Chem. 1996, 61, 7585-7592. (i) Bordunov, A. V.; Bradshaw, J .
S.; Zhang, X. X.; Dalley, N. K.; Kou, X.; Izatt, R. M. Inorg. Chem. 1996,
3, 7229-7240. (j) Kubo, K.; Kato, N.; Sakurai, T. Bull. Chem. Soc. J pn.
1997, 70, 3041-3046. (k) Prodi, L.; Bolletta, F.; Montalti, M.; Zac-
cheroni, N. Tetrahedron Lett. 1998, 5451-5454.
1
substitution. Figure 1 shows H NMR of the phenyl and
Cp protons for compounds 1, 2d , 3e, and 4e. Compound
1 shows two singlets: the phenyl proton singlet is at 7.0
ppm, and the Cp singlet is at 5.5 ppm. After one crown
ether is attached, the phenyl singlet is split into two
doublets at 6.5 and 6.1 ppm; the Cp singlet shifts to
higher field at 5.1 ppm. After the second amine is
attached, the phenyl proton doublets become an AB
quartet and shift to 5.8 ppm; the Cp singlet shifts to
around 5.0 ppm. After demetalation the phenyl proton
AB quartet shifts to around 6.6 to 6.9 ppm.
J . Org. Chem, Vol. 68, No. 6, 2003 2163

Pearson and Xiao
were obtained for crude metal complexes, and only values for
phenyl and Cp protons are reported because of the presence
of residual crown ether and amine. The mass for metal
complexes is M - PF6, the mass for molecules containing Cl
is reported for 35Cl.
SCHEME 2
Im p r oved Syn th esis of 1. To a 250-mL three-neck round-
bottom flask was added p-dichlorobenzene (40 g, 272 mmol)
and 15 mL of n-heptane. The mixture was heated to 55-60
°C until p-dichlorobenzene completely melted. Ferrocene (freshly
sublimed, 3.14 g, 16.9 mmol), aluminum powder (400 mg, 14.8
mmol), AlCl3 (6 g, 45 mmol), and water (288 µL, 16 mmol) were
added sequentially with vigorous stirring. The mixture was
held at 55 °C for 8 h, and then heated to 95 °C for 8 h. The
dark blue slurry was cooled to room temperature, and 40 mL
of water was added slowly, followed by 30 mL of ether. The
mixture was stirred for 10 min and partitioned. The aqueous
phase was extracted with ether until the ether was almost
colorless, and saturated aqueous NH4PF6 was added to the
aqueous phase dropwise until no further yellow precipitate
appeared. The product was filtered off and dried under vacuum
(2.4 g, 35%).
[(η5-Cyclopen tadien yl)(η6-(1-ch lor o-4-(4,7,10,13-tetr aoxa-
1-a za cyclop en ta d ecyl))ben zen e)]ir on Hexa flu or op h os-
p h a te (2a ). To a round-bottom flask was added compound 1
(324 mg, 0.78 mmol) and 1-aza-15-crown-5 (500 mg, 2.3 mmol),
and the flask was flushed with argon. Pyridine (1 mL) and
THF (10 mL) were added. The resulting mixture was stirred
at room temperature for 5 days. The mixture was then filtered
through Celite. THF was removed by rotary evaporation, and
the red-orange residue was washed with ether (3 × 30 mL).
The crude product was divided into two portions and used
1
directly for preparing complex 3a or 3b. H NMR (200 MHz,
CD3COCD3): δ 6.23 (2H, d, J ) 6.8), 5.89 (2H, d, J ) 6.8),
4.94 (5H, s). HRMS-FAB: calcd for C21H29O4NClFe 450.1134,
found 450.1132.
different from the monoazacrown ether and p-phenyl
diaza-18-c-6 derivatives.
Taking advantage of monoarylation of the diazacrown
ether, compounds 10a , 10b, and 10c were made in four
steps from compound 1 (Scheme 2).17 After the first
amination, the residue is washed with ethyl ether several
times to remove excess crown ether. After the second
crown amine is attached to R, the product mixture is
again washed with ethyl ether and benzene to remove
excess RX. Following this procedure can greatly reduce
the amount of byproducts.
[(η5-Cyclop en t a d ien yl)(η6-(1-p ip er a zin o-4-(4,7,10,13-
tetr a oxa -1-a za cyclop en ta d ecyl))ben zen e)]ir on Hexa flu -
or op h osp h a te (3a ). To complex 2a (118 mg) in 4 mL of
CH3CN was added piperazine (3.3 equiv). The mixture was
stirred at room temperature for 2 days, then filtered through
Celite, and CH3CN was removed. The dark red residue was
washed with ether (40 mL). The crude product was submitted
directly to demetalation.1H NMR (200 MHz, CD3COCD3): δ
5.55 (4H, br s), 4.82 (5H, s). HRMS-FAB: calcd for C25H38O4N3-
Fe 500.2212, found 500.2212.
p-Phenylenediamine derivatives 4a -f and 10a -c be-
come deep blue when treated with UV light or acid, which
indicates that they all form the Wu¨rster’s blue radical
cation.6 5a , 5b, 6, and 7 do not show the blue color that
is consistent with the corresponding aromatic ring being
less electron rich.
As mentioned in the Introduction, previous studies
have indicated that these compounds can be useful as
molecular devices. Detailed studies on the above systems
in the synthesis of PET fluorescent chemosensors and
molecular switches will be reported elsewhere.
1-P ip er a zin o-4-(4,7,10,13-t et r a oxa -1-a za cyclop en t a -
d ecyl)ben zen e (4a ). The crude 3a from above was dissolved
in 40 mL of CH3CN in a round-bottom flask with condenser
and irradiated with a 100-W Q-beam halogen lamp for 4 h.
The mixture was filtered through Celite. The solvent was
removed by rotary evaporation, and the residue was purified
by flash chromatography (silica gel, CH2Cl2/CH3OH/Et3N 90/
5/5, Rf 0.3) to afford 4a as red oil (48 mg, 63% overall yield
1
from 1). H NMR (200 MHz, CDCl3): δ 6.85 (2H, d, J ) 9.0),
6.48 (2H, d, J ) 9.0), 6.18 (1H, br), 3.5-3.8 (20H), 3.0-3.2
(8H, s + t, J ) 4.9). 13C NMR (50 MHz, CDCl3): δ 143.2, 141.8,
119.6, 112.4, 71.3, 70.2, 70.0, 69.8, 69.6, 68.8, 67.4, 52.6, 50.6,
48.1, 45.0. HRMS-FAB: calcd for C20H34O4N(MH+) 380.2549,
found MH+ 380.2556.
Exp er im en ta l Section
1-Ch lor o-4-(4,10,13-t r ioxa -1,7-d ia za cyclop en t a d ecyl)-
ben zen e (5a ). One portion of the above product (157 mg, 0.24
mmol) was dissolved in 35 mL of CH3CN and irradiated with
a 100-W Q-beam halogen lamp for 3 h. The solvent was
removed by rotary evaporation, and the residue was purified
by flash chromatography (silica gel, acetone/hexanes/Et3N 1/1/
0.1, Rf 0.2), to afford the product as a pale yellow oil (53 mg,
All reactions were conducted under nitrogen or argon.
Reaction flasks except those for demetalation were covered
with aluminum foil. Solvents for all reactions were freshly
distilled before use: THF over sodium/benzophenone, CH2Cl2,
CH3CN, Et3N and pyridine over CaH2. All reagents were used
as purchased unless otherwise noted. NMR spectra were
recorded on 200 or 300 MHz instruments. Chemical shifts are
reported in ppm with solvent as the internal reference, and
1
67% yield from 1). H NMR (200 MHz, CDCl3): δ 7.15 (2H, d,
J ) 8.8), 6.60 (2H, d, J ) 8.8), 4.52 (1H, br), 3.5-3.8 (16H),
3.03 (4H, t, J ) 4.7). 13C NMR (50 MHz, CDCl3): δ 146.7, 129.1,
121.4, 113.5, 70.8, 70.1, 69.3, 69.0, 68.4, 67.4, 52.6, 48.3.
HRMS-FAB: calcd for C16H26N2O3Cl (MH+) 329.1632, found
MH+ 329.1615.
1
coupling constants are reported in Hz. Only H NMR spectra
(17) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 3rd ed.; Wiley-Interscience: New York, 1999.
2164 J . Org. Chem., Vol. 68, No. 6, 2003

Preparation of N-Aryl Azacrown Ether Derivatives
1-(4-Hyd r oxyp ip er a zin o)-4-(4,7,10,13-tetr a oxa -1-a za cy-
clop en ta d ecyl)ben zen e (4b). Similar to 4a . 1H NMR (200
MHz, CD3COCD3): δ 6.85 (2H, d, J ) 9.1), 6.61 (2H, d, J )
reflux for 5 h, then cooled and filtered through Celite. CH3CN
was removed by rotary evaporation, and the residue was taken
up in acetone and filtered. Excess piperidine and acetone were
removed by rotary evaporation. Without further purification,
9.1), 3.4-3.7 (22H), 3.4 (2H), 2.69 (2H), 1.9 (2H), 1.6 (2H). 13
C
1
NMR (50 MHz, CD3COCD3): δ 143.9, 143.3, 120.0, 113.4, 72.0,
71.2, 70.9, 70.8, 69.8, 68.0, 53.4, 50.2, 35.8. HRMS-FAB: calcd
for C21H34O5N2 394.2468, found 394.2469.
1-(4-P ip er a zin o)-4-(4,7,10,13,16-p en t a oxa -1-a za cyclo-
p en ta d ecyl)ben zen e (4c). Similar to 4a . 1H NMR (200 MHz,
CD3COCD3): δ 6.84 (2H, d, J ) 9.2), 6.67 (2H, d, J ) 9.2),
3.4-3.7 (24H), 3.02 (1H, s), 2.91 (8H, s). 13C NMR (50 MHz,
CD3COCD3): δ 144.5, 143.6, 119.3, 114.0, 71.7, 71.6, 71.5, 69.9,
52.9, 52.6, 47.2. HRMS-FAB: calcd for C22H38O5N3 (MH+)
424.2811, found MH+ 424.2793.
the crude product was submitted directly to demetalation. H
NMR (200 MHz, CD3COCD3): δ 5.94 (1H, t, J ) 6.5), 5.79 (1H,
s), 5.70 (2H, d, J ) 5.4), 4.88 (5H, s). HRMS-FAB: calcd for
C
28H44O4N3ClFe 542.2681, found 542.2661. The product was
dissolved in 50 mL CH3CN, and irradiated with 100 W Q-beam
halogen lamp for 35 min. The solvent was removed by rotary
evaporation, and the residue was purified by flash chroma-
tography (silica gel, acetone/Et3N: 15/1, Rf ) 0.2), to afford 7
as yellow oil (272 mg, 96% overall yield from the starting
1
complex). H NMR (200 MHz, CDCl3): δ 7.12 (1H, t, J ) 8.0),
6.35 (1H, dd, J ) 8.0, 2.0), 6.31 (1H, d, J ) 2.0), 6.24 (1H, dd,
J ) 8.0, 2.0), 4.64 (2H, s), 3.58 (24H), 2.88 (4H, t, J ) 5.8), 1.6
(6H). 13C NMR (50 MHz, CDCl3): δ 154.7, 150.5, 130.4, 106.4,
104.9, 102.1, 71.3, 71.1, 69.9, 68.8, 52.0, 51.7, 49.2, 26.9, 25.4.
1-P ip er id in o-4-(4,10,13-tr ioxa -1,7-d ia za cyclop en ta d ec-
yl)ben zen e (4d ). Similar to 4a . 1H NMR (200 MHz, CD3-
COCD3): δ 6.84 (2H, d, J ) 9.0), 6.64 (2H, d, J ) 9.0), 3.4-3.7
(16H), 2.94 (4H, t, J ) 5.4), 2.70 (4H), 2.2 (1H, br), 1.4-1.7
(6H). 13C NMR (50 MHz, CD3COCD3): δ 145.1, 143.6, 119.9,
114.1, 71.9, 71.2, 70.9, 70.4, 70.1, 69.8, 53.9, 53.6, 53.2, 49.7,
49.5, 27.2, 25.2. HRMS-FAB: calcd for C21H36O3N3 (MH+)
378.2756, found MH+ 378.2756.
HRMS-FAB Calculated for
C
23H40O4N2 (MH+) 422.3019;
Found MH+ 422.3011.
[(η5-Cyclopen tadien yl)(η6-(1-ch lor o-4-(4,7,13,16-tetr aoxa-
1-a cetyl-10-d ia za cycloocta d ecyl))ben zen e)]ir on Hexa flu -
or op h osp h a te (8a ). Crude complex 2d (750 mg, 1.0 mmol)
was dissolved in 10 mL of CH2Cl2, the flask was cooled with
ice, Ac2O (1 mL, 10 equiv) and Et3N (2 mL, 14 equiv) were
added, then the mixture was warmed to room temperature and
stirred overnight. The reaction mixture was rotary evaporated
and the residue was washed with ether. Without further
1-Ch lor o-4-(4,7,13,16-tetr a oxa -1,10-d ia za cycloocta d ec-
1
yl)ben zen e (5b). Similar to 5a . H NMR (300 MHz, CDCl3):
δ 7.11 (2H, q, J ) 9.2), 6.58 (2H, q, J ) 9.2), 3.6 (20H), 2.80
(4H, t, J ) 4.8), 2.21 (1H, br, s). 13C NMR (200 MHz, CDCl3)
δ 146.6, 129.0, 120.6, 112.8, 70.6, 70.5, 70.5, 68.6, 50.8, 49.4.
HRMS-FAB: calcd for C18H30O4N2Cl (MH+) 373.1894, found
MH+ 373.1891.
1
purification, the crude product was used for preparing 9a . H
1-P ip er id in o-4-(4,7,13,16-tetr a oxa -1,10-d ia za cycloocta -
d ecyl)ben zen e (4e). Similar to 4a . 1H NMR (200 MHz, CD3-
COCD3): δ 6.84, and 6.65 (2H each, d, J ) 9.2), 3.45-3.70
(20H), 2.94 (4H, t, J ) 5.3), 2.71 (4H, t, J ) 4.8), 1.43-1.7
(6H). 13C NMR (50 MHz, CD3COCD3): δ 144.9, 143.7, 120.0,
114.0, 71.5, 71.4, 71.3, 53.3, 52.1, 50.4, 27.2, 25.2. HRMS-
FAB: calcd for C23H40O4N3 (MH+) 422.3019, found MH+
422.3010.
NMR (300 MHz, CDCl3): δ 7.11 (2H, d, J ) 9.2), 6.57 (2H, d,
J ) 9.2), 5.38 (5H, s). HRMS-FAB: calcd for C25H35O5ClN2Fe
(M - H) 535.1662, found M - H 535.1643.
[(η5-Cyclop en t a d ien yl)(η6-(1-p ip er a zin o-4-(4,7,13,16-
t e t r a oxa -1-a ce t yl-10-d ia za cyclooct a d e cyl))b e n ze n e )]-
ir on h exa flu or op h osp h a te (9a ). The above crude 8a (1
mmol) was dissolved in 15 mL of CH3CN, piperazine (5 equiv)
was added, and the mixture was heated to reflux for 6 h, then
cooled and filtered through Celite. The filtrate was dried by
rotary evaporation, and the residue was washed with ether
(30 mL). Without further purification, the dark-red residue
1-(4-Hyd r oxyp ip er id in o)-4-(4,7,10,13-tetr a oxa -1,10-d i-
a za cycloocta d ecyl)ben zen e (4f). Similar to 4a . 1H NMR
(300 MHz, C6D6): δ 6.92 (2H, d, J ) 9.1), 6.61 (2H, d, J )
9.1), 3.2-3.6 (23H), 2.69 (6H), 2.35 (2H, br), 1.8 (2H), 1.7 (2H).
13C NMR (50 MHz, C6D6): δ 144.1, 143.3, 119.9, 114.3, 71.1,
70.8, 69.7, 67.7, 52.0, 49.9, 35.5. HRMS-FAB: calcd for
1
was submitted directly to demetalation. H NMR (200 MHz,
CD3COCD3): δ 5.75 (4H, q, J ) 5.7), 4.98 (5H, s). HRMS-
FAB: calcd for C32H45O5N4Fe 585.2739, found 585.2719.
C
23H40O5N2 (MH+) 438.2968, found MH+ 438.2963.
1-P ip er a zin o-4-(4,7,13,16-tetr a oxa -1-a cetyl-10-d ia za cy-
cloocta d ecyl)ben zen e (10a ). The above crude 9a was dis-
solved in 30 mL of CH3CN and irradiated with a 100-W
Q-beam halogen lamp for 45 min. The mixture was filtered
through Celite, and the solvent was removed by rotary
evaporation. The residue was purified by flash chromatography
(silica gel, CH2Cl2/Et3N/CH3OH 30/1/1, Rf 0.2) to afford 10a
as an orange oil (226 mg, 53% yield from 1). 1H NMR (300
MHz, CDCl3): δ 6.87 (2H, d, J ) 9.0), 6.65 (2H, d, J ) 9.0),
3.63 (24H, s), 3.0 (8H, s), 2.51 (1H, br), 2.09 (3H, s). 13C NMR
(50 MHz, CDCl3): δ 169.8, 144.5, 143.3, 119.4, 114.1, 71.4,
71.2, 71.1, 71.1, 70.8, 70.4, 70.1, 69.8, 52.7, 52.5, 50.0, 47.4,
46.8, 21.6. HRMS-FAB: calcd for C24H40O5N4 464.2999, found
464.3005.
1-Ch lor o-3-(1-(4,7,13,16-tetr a oxa -1,10-d ia za cycloocta -
d ecyl))ben zen e (6). To a round-bottom flask were added [(η5-
cyclopentadienyl)(η6-1,3- dichlorobenzene)]iron hexafluoro-
phosphate (526 mg, 1.3 mmol) and 1,10-diaza-18-crown-6 (1.0
g, 3.8 mmol). The flask was flushed with argon, then 1 mL of
pyridine and 15 mL of CH2Cl2 were added. The resulting
mixture was heated to reflux overnight. The solution was
filtered through Celite, the solvent was removed by rotary
evaporation, and the residue was washed with ether (3 × 50
mL). The crude product was divided into two portions and used
for preparing 6 and 7. 1H NMR (200 MHz, CD3COCD3): δ 6.4
(2H, br s), 6.28 (1H, br t), 5.95 (1H), 5.11 (5H,s). HRMS-FAB:
calcd for C23H34O4N2ClFe 493.1556, found 493.1543. One
portion of the above complex (406 mg, 0.6 mmol) was dissolved
in 30 mL of CH3CN and irradiated with a 100-W Q-beam
halogen lamp for 10 min. The solvent was removed by rotary
evaporation, and the residue was purified by flash chroma-
tography (silica gel, CH2Cl2/Et3N/CH3OH 10/1/1, Rf 0.5) to
afford 6 as a yellow oil (152 mg, 68% overall yield from the
[(η5-Cyclopen tadien yl)(η6-(1-ch lor o-4-(4,7,13,16-tetr aoxa-
1-ben zoyl-10-diazacyclooctadecyl))ben zen e)]ir on Hexaflu -
or op h osp h a te (8b). One portion of crude 2d (300 mg, 0.22
mmol) was dissolved in 2 mL of CH3CN, the flask was cooled
with ice, then benzoyl chloride (70 µL, 0.6 mmol) and pyridine
(0.1 mL) were added. The mixture was warmed to room
temperature and stirred for 5 h, then refluxed for 1 h. The
reaction mixture was cooled and filtered through Celite, and
the solvent was removed by rotary evaporation. The dark red
residue was washed with benzene and ether. Without further
1
starting complex). H NMR (200 MHz, CDCl3): δ 7.08 (1H, t,
J ) 8.2), 6.5-6.6 (3H), 3.60 (20H), 2.79 (4H, t, J ) 4.8), 2.25
(1H, br). 13C NMR (50 MHz, CDCl3): δ 149.1, 135.2, 130.22,
115.7, 111.4, 109.7, 70.6, 70.5, 50.6, 49.4. HRMS-FAB: calcd
for C18H30O4N2Cl 373.1894, found MH+ 373.1900.
1
purification, the residue was used for preparing 9b. H NMR
1-P ip er id in o-3-(4,7,13,16-tetr a oxa -1,10-d ia za cycloocta -
d ecyl)ben zen e (7). One portion of the preceding intermediate
(458 mg, 0.67 mmol) was dissolved in 15 mL of CH3CN and
piperidine (10 equiv) was added. The mixture was heated to
(200 MHz, CD3CN): δ 7.41(5H, s), 6.48 (2H, d, J ) 6.9), 6.01
(2H, d, J ) 6.9), 5.1 (5H, s). HRMS-FAB: calcd for C30H38O5-
ClN2Fe 597.1820, found 597.1820.
J . Org. Chem, Vol. 68, No. 6, 2003 2165

Pearson and Xiao
1-P ip er a zin o-4-(4,7,13,16-tetr a oxa -1-ben zoyl-10-d ia za -
cycloocta d ecyl)ben zen e (10b). Similar to 10a . 1H NMR (300
MHz, CD3COCD3): δ 7.44 (5H, s), 6.88 (2H, d, J ) 9.1), 6.70
(2H, d, J ) 9.1), 3.58 (25H), 3.02 (8H, s). 13C NMR (75 MHz,
CD3COCD3): δ 171.9, 144.1, 143.7, 138.5, 129.7, 129.1, 127.5,
119.3, 113.9, 71.5, 70.0, 52.4, 52.0, 46.4. HRMS-FAB: calcd
for C29H43O5N4 (MH+) 527.3233, found MH+ 527.3233.
1-P ip er a zin o-4-(4,7,13,16-tetr a oxa -1-ben zyl-10-d ia za cy-
cloocta d ecyl)ben zen e (10c). Similar to 10a . H NMR (200
1
MHz, CD3COCD3): δ 7.30 (5H), 6.84 (2H, d, J ) 9.2), 6.68 (2H,
d, J ) 9.2), 3.5-3.7 (22H), 2.92 (8H, s), 2.82 (1H, br), 2.80 (4H,
t, J ) 4.9). 13C NMR (75 MHz, CD3COCD3): δ 144.1, 143.1,
141.2, 129.5, 128.9, 127.4, 119.2, 114.0, 71.6, 71.3, 70.8, 69.9,
60.5, 54.7, 52.7, 52.4, 47.0. HRMS-FAB: calcd for C29H45O4N4
(MH+) 513.3441, found MH+ 513.3432.
[(η5-Cyclopen tadien yl)(η6-(1-ch lor o-4-(4,7,13,16-tetr aoxa-
1-ben zyl-10-diazacyclooctadecyl))ben zen e)]ir on Hexaflu -
or op h osp h a te (8c). One portion of 2d (190 mg, 0.22 mmol)
and Na2CO3 (64 mg, 0.6 mmol) were dissolved in 2 mL of CH3-
CN, the flask was cooled with ice, and PhCH2Br (70 µL, 0.58
mmol) was added. The mixture was warmed to room temper-
ature and stirred for 5 h, then heated to reflux for 1 h. The
reaction mixture was cooled to room temperature, and filtered
through Celite. The solvent was removed by rotary evapora-
tion, and the yellow residue was washed with benzene and
ether. Without further purification, the crude product was used
Ack n ow led gm en t. We are grateful to the Petro-
leum Research Fund, administered by the American
Chemical Society, for financial support.
Su p p or tin g In for m a tion Ava ila ble: Detailed experi-
mental procedure for 2b-d , 3b-f, 4b-f, 5b, 9b,c, and
10b,c;1H and 13C NMR spectra of 4a -f, 5a ,b, 6, 7, and 10a -
c. This material is available free of charge via the Internet at
http://pubs.acs.org.
1
directly for preparing 9c. H NMR (200 MHz, CD3CN): δ 7.6
(m), 6.37 (2H, d, J ) 6.9), 5.84 (2H, d, J ) 6.9), 4.98 (5H, s).
HRMS-FAB: calcd for
583.2007.
C30H40O4ClN2Fe 583.2026, found
J O020527P
2166 J . Org. Chem., Vol. 68, No. 6, 2003