EPR probes with well-defined, long distances between two or three unpaired electrons

Article abstract of DOI:10.1021/jo005556j

The synthesis of rod- and star-shaped compounds carrying two or three spin labels as end groups is described. The unpaired electrons are 2.8-5.1 nm apart from each other. The shape-persistent scaffolds were obtained through Pd-Cu-catalyzed alkynyl-aryl coupling and Pd-Cu-catalyzed, alkyne dimerization in the presence of oxygen using p-phenyleneethynylene as the basic shape-persistent building block. The spin label 1-oxyl-2,2,5,5-tetramethylpyrroline-3-carboxylic acid (4) was attached through esterification of the terminal phenolic OH groups of the scaffold.

Full text of DOI:10.1021/jo005556j

J . Org. Chem. 2000, 65, 7575-7582
7575
EP R P r obes w ith Well-Defin ed , Lon g Dista n ces betw een Tw o or
Th r ee Un p a ir ed Electr on s
Adelheid Godt,* Corinna Franzen, Stephan Veit, Volker Enkelmann, Matthias Pannier, and
Gunnar J eschke
Max-Planck-Institut fu¨r Polymerforschung, Ackermannweg 10, D-55128 Mainz, Germany
godt@mpip-mainz.mpg.de
Received J une 26, 2000
The synthesis of rod- and star-shaped compounds carrying two or three spin labels as end groups
is described. The unpaired electrons are 2.8-5.1 nm apart from each other. The shape-persistent
scaffolds were obtained through Pd-Cu-catalyzed alkynyl-aryl coupling and Pd-Cu-catalyzed
alkyne dimerization in the presence of oxygen using p-phenyleneethynylene as the basic shape-
persistent building block. The spin label 1-oxyl-2,2,5,5-tetramethylpyrroline-3-carboxylic acid (4)
was attached through esterification of the terminal phenolic OH groups of the scaffold.
In tr od u ction
3,9-diene-1,5,7,11-tetrayne,16 1,4-diethynylbenzene,16-18
1,4-bis(4-ethynylphenyl)butadiyne,16,18 or 2,6-dihydroxy-
anthrachinone19 and the spin labels 1-oxyl-2,2,6,6-tet-
ramethylpiperidine-4-yl,18 1-oxyl-2,2,6,6-tetramethylaza-
cyclohex-3-en-4-yl,17,18 and 1-oxyl-2,2,5,5-tetramethylpyrro-
line-3-yl.12,19 The lately developed, very efficient strate-
gies for the preparation of monodisperse rod-shaped
compounds such as oligo(p-phenyleneethynylene)s (oligo-
PPE)20-22 and oligo(p-phenylene)s23 with a wide range of
lengths are an ideal starting point for the synthesis of
well-defined biradicals with a larger spacing between the
two unpaired electrons. Furthermore, these strategies
offer a convenient access to molecules with architectures
other than rods.22,24 For instance, star-shaped triradicals
are required to check whether and how precisely the
angle between molecular fragments with a distance in
the nanometer range can be determined by EPR. Such
angle measurements could finally be used to determine
the relative orientation of protein subunits or dendrimer
arms. Herein we report on the preparation of the biradi-
cals 1 and 2a ,b with a spacing of 2.8-5.1 nm12 and of
the star-shaped triradical 3 with p-phenyleneethynylene
as the building block for the spacer and 1-oxyl-2,2,5,5-
tetramethylpyrroline-3-yl as the spin label.
Electron paramagnetic resonance (EPR) is a versatile
tool for investigating structure and dynamics of biomol-
ecules such as proteins1-3 and DNA4,5 and of synthetic
polymers.6-9 Important information can be obtained for
example by measuring the distance between two or more
radicals attached at specific sites of the macromolecule.3,10
To broaden the scope of such EPR techniques new pulse
sequences are developed and existing sequences are
improved.11-14 To explore the potential of new pulse
sequences and to assess the upper limit of the measurable
distances between unpaired electrons, well-defined com-
pounds are highly desirable. The term “well-defined”
particularly addresses the distance between the unpaired
electrons. In the past, biradicals with distances of up to
2.77 nm were prepared. They are based on spacers such
as tetraphenylporphyrin,15 hex-3-ene-1,5-diyne,16 dodeca-
(1) Spin Labeling II. Methods and Applications; Berliner, L. J ., Ed.;
Academic Press: New York, 1979.
(2) Shin, Y. K.; Levinthal, C.; Levinthal, F.; Hubbel, W. L. Science
1993, 259, 960.
(3) Hustedt, E. J .; Beth, A. H. Annu. Rev. Biophys. Biomol. Struct.
1999, 28, 129.
(4) Robinson, B. H.; Mailer, C.; Drobny, G. Annu. Rev. Biophys.
Biomol. Struct. 1997, 26, 259.
(5) Spaltenstein, A.; Robinson, B. H.; Hopkins, P. B. J . Am. Chem.
Soc. 1988, 110, 1299; 1989, 111, 2303.
(6) Miller, W. G. in ref 1, p 173.
(7) Molecular Motion in Polymers by ESR; Boyer, R. F.; Keinath, S.
E., Eds.; Hanwood: Chur, 1980.
(8) Cameron, G. G. In Comprehensive Polymer Science; Booth, C.,
Price, C., Eds.; Pergamon Press: London, 1989; Vol. 1, Chapter 23.
(9) Hill, D. J . T.; O’Donnell, J . H.; Pomery, P. J . Electron Spin Reson.
1992, 13A, 202.
(10) Eaton, G. R.; Eaton, S. S. In Biological Magnetic Resonance;
Berliner; L. J ., Reuben, J ., Eds.; Plenum: New York, 1989; Vol. 8, p
339.
(11) Milov, A. D.; Maryasov, A. G.; Tsvetkov, Y. D. Appl. Magn.
Reson. 1998,15, 107.
(12) J eschke, G.; Pannier, M.; Godt, A.; Spiess, H. W. Chem. Phys.
Lett., submitted.
(13) Pannier, M.; Veit, S.; Godt, A.; J eschke, G.; Spiess, H. W. J .
Magn. Reson. 2000, 142, 331.
(14) Pannier, M.; Scha¨dler, V.; Scho¨ps, M.; Wiesner, U.; J eschke,
G.; Spiess, H. W. Macromolecules, submitted.
(15) Rakowsky, M. H.; More, K. M.; Kulikov, A. V.; Eaton, G. R.;
Eaton, S. S. J . Am. Chem. Soc. 1995, 115, 2049.
(16) Martin, R. E.; Pannier, M.; Diederich, F.; Gramlich, V.; Hubrich,
M.; Spiess, H. W. Angew. Chem., Int. Ed. Engl. 1998, 37, 2834.
Resu lts a n d Discu ssion
1-Oxyl-2,2,5,5-tetramethylpyrroline-3-carboxylic acid
(4) was selected as the spin label for reasons of avail-
(17) Torii, S.; Hase, T.; Kuroboshi, M.; Amatore, C.; J utand, A.;
Kawafuchi, H. Tetrahedron Lett. 1997, 38, 7391.
(18) Pavlikov, V. V.; Shapiro, A. B.; Rozantsev, E. G. Izv. Akad. Nauk
SSSR, Ser. Khim. 1980, 128; Bull. Acad. Sci. USSR Div. Chem. Sci.
(Engl. Transl.) 1980, 29, 113. Kokorin, A. I.; Pavlikov, V. V.; Shapiro,
A. B. Dokl. Akad. Nauk SSSR 1980, 253, 147.
(19) Larsen, R. G.; Singel, D. J . J . Chem. Phys. 1993, 98, 5134.
Pfannebecker, V.; Klos, H.; Hubrich, M.; Volkmer, T.; Heuer, A.;
Wiesner, U.; Spiess, H. W. J . Phys. Chem. 1996, 100, 13428.
(20) Kukula, H.; Veit, S.; Godt, A. Eur. J . Org. Chem. 1999, 277.
Ziener, U.; Godt, A. J . Org. Chem. 1997, 62, 6137.
(21) J ones, L., II; Schumm, J . S.; Tour, J . M. J . Org. Chem. 1997,
62, 2, 1388. Huang, S.; Tour, J . M. J . Org. Chem. 1999, 64, 8898.
(22) Moore, S. Acc. Chem. Res. 1997, 30, 402.
(23) Liess, P.; Hensel, V.; Schlu¨ter, A.-D. Liebigs Ann. 1996, 1037.
(24) For example, Prince, R. B.; Okada, T.; Moore, J . S. Angew.
Chem., Int. Ed. 1999, 38, 233. Yao, Y.; Tour, J . M. J . Org. Chem. 1999,
64, 1968. Mongin, O.; Gossauer, A. Tetrahedron 1997, 53, 6835.
Mongin, O.; Papamicae¨l, C.; Hoyler, N.; Gossauer, A. J . Org. Chem.
1998, 63, 5569.
10.1021/jo005556j CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/12/2000

7576 J . Org. Chem., Vol. 65, No. 22, 2000
Godt et al.
Sch em e 1a
ability, easily addressable carboxylic acid functionality,
its restricted conformational flexibility, and the expected
low exchange coupling. A restricted conformational flex-
ibility is important to allow for a well-defined spacing.
Hence, 3-ethynyl-1-oxyl-2,2,5,5-tetramethylpyrroline25 and
the corresponding six-membered-ring compound 4-ethy-
nyl-1-oxyl-2,2,6,6-tetramethylazacyclohex-3-en26 might be
even better labels when attached to oligoPPEs through
an alkynyl-aryl coupling.27 However, if one considers the
exchange coupling between the unpaired electron spins
these labels are less favorable. The exchange coupling
should be much smaller than the dipole-dipole coupling.
Otherwise, the measurement of the distance will be more
complicated and the precision that can be achieved will
be lowered. Spin label 4 is expected to couple less
unpaired spin density into the conjugated scaffold than
the other labels mentioned above.18 Furthermore, calcu-
lations show that the error of the distance measurements
by EPR is in the range or larger than the uncertainty of
the spacing of the unpaired electron spins due to different
conformers when using 4 as the spin label, especially for
distances larger than 3 nm.12
A functionality that corresponds to the carboxylic acid
group of the spin label 4 is the phenolic OH group. Thus,
appropriate rod-shaped diphenols were prepared. The
smallest diphenol 8 was obtained through an alkynyl-
aryl coupling of protected monophenol 5 and diiodo
compound 6 and subsequent removal of the tetrahydro-
pyran-2-yl protecting groups from coupling product 7
(Scheme 1).28
The analogous approach to longer diphenols with five
or seven phenyleneethynylene units through a reaction
starting from protected monophenol 13 and diiodo com-
pound 6 should be possible. However, it is expected that
separation of the intended products and the butadiynes
14, which will be formed as byproducts,20,30 will be rather
troublesome because of very similar polarity. Another
option is the preparation of a sufficiently long oligoPPE
9 with n ) 3 or 5, successive deprotections of the alkyne
moieties and couplings with iodophenol 11. A very
different, much more straightforward approach to long,
rod-shaped diphenols is the oxidative dimerization of
protected monophenols 13 which yields the protected
diphenols 14 that are finally O-deprotected to obtain the
diphenols 15 (Scheme 2). The protected monophenols 13
were prepared through coupling of TIPS-protected oli-
goPPEs 10 with protected iodophenol 11 followed by the
a
Key: (a) Pd(PPh3)2Cl2, CuI, Et2NH (74%); (b) TsOH, methanol,
THF (85%); (c) DCC, DMAP, THF (76%).
reaction of the obtained monofunctionalized oligoPPEs
12 with n-Bu4NF in THF. Protected monophenol 13a was
also synthesized via the reaction of protected monophenol
5 with iodo compound 16 and subsequent removal of the
hydroxymethyl group from coupling product 17 through
treatment with MnO2 and powdered KOH. However, in
this case the overall yield is lower than with the former
strategy and chromatographic purification of 17 turned
out to be difficult.
The protected monophenols 13 can be dimerized through
treatment with CuCl and CuCl2 in pyridine.31 However,
these reactions were very slow. They took several days
for completion and yielded mixtures of protected diphe-
nols 14 and partially O-deprotected diphenols. The reac-
tion with CuCl, TMEDA in THF at air32 resulted in
incomplete conversion and in the formation of side
products. For the coupling reactions of alkynes 10 with
iodobenzene derivatives such as 6 or 16 the alkynes 10
had been used in excess. Nevertheless, no residual
alkynes 10 but their oxidative dimerization products, i.e.,
the butadiyne derivatives, were detected in the reaction
product mixture.20 This observation led to the idea of
using the conditions of alkynyl-aryl coupling for pur-
poseful alkyne dimerization. Dimerization, also called
homocoupling, of terminal alkynes as a side reaction in
alkynyl-aryl coupling reactions in the presence of Pd
complexes and CuI is well documented.20,30 Nonetheless,
we found only a few reports on making use of these
reaction conditions for alkyne dimerization.33-38 Chloro-
(25) Kalai, T.; Balog, M.; J ekoe, J .; Hideg, K. Synthesis 1999, 973.
(26) Hamill, G. P.; Yost, E. A.; Sandman, D. J . Mol. Cryst. Liq. Cryst.
Sci. Technol., Sect. A 1992, 211, 339.
(27) Examples for alkynyl-aryl coupling with 3-ethynyl-1-oxyl-
2,2,5,5-tetramethylpyrroline: Kirchner, J , J .; Hustedt, E. J .; Robinson,
B. H.; Hopkins, P. B. Tetrahedron Lett. 1990, 31, 593 See also ref 5.
(28) We have not tested whether unprotected 4-ethynylphenol (ref
29) can be coupled with diiodo compound 6. Unprotected 4-ethynylphe-
nol is reported to be very susceptible to hydration. In contrast, 5 could
be stored for several month without any sign of decomposition.
According to ref 29, for preparing 4-ethynylphenol from 4-iodophenol
and trimethylsilylethyne (20) the latter reagent was used in large
excess. As we found, this is necessary because first the phenol is
silylated by 20 and then the resulting O-silylylated 4-iodophenol reacts
with 20 through alkynyl-aryl coupling. The waste of precious 20 and
problems associated with the reactivity of the final compound can be
avoided by using the THP-protected iodophenol.
(31) O’Krongly, D.; Denmeade, S. R.; Chiang, M. Y.; Breslow, R. J .
Am. Chem. Soc. 1985, 107, 5544.
(32) Hay, A. S. J . Org. Chem. 1962, 27, 3320.
(33) Rødbotten, S.; Benneche, T.; Undheim K. Acta Chem. Scand.
1997, 51, 873.
(29) Chang, J . Y.; Yeon, J . R.; Shin, Y. S.; Han, M. J .; Hong, S.-K.
Chem. Mater. 2000, 12, 1076.
(30) E.g., McGaffin, G.; de Meijere, A. Synthesis 1994, 583. Shultz,
D. A.; Gwaltney, K. P.; Lee, H. J . Org. Chem. 1998, 63, 4034. Ma, L.;
Hu, Q.-S.; Vitharana, D.; Wu, C.; Kwan, C. M. S.; Pu, Li. Macromol-
ecules 1997, 30, 204. Bharathi, P.; Patel, U.; Kawaguchi, T.; Pesak, D.
J .; Moore, J . S. Macromolecules 1995, 28, 5955.
(34) Wagner, R. W.; J ohnson, T. E.; Li, F, Lindsey, J . S. J . Org.
Chem. 1995, 60, 5266.
(35) Brickmann, K.; Hambloch, F.; Suffert, J .; Brueckner, R. Lieb.
Ann. 1996, 457.
(36) Liu, Q.; Burton, D. J . Tetrahedron Lett. 1997, 38, 4371.

Synthesis of EPR Probes
J . Org. Chem., Vol. 65, No. 22, 2000 7577
Sch em e 2a
a
Key: (a) MnO2, KOH, Et2O (10: 75-80%, 13a : 94%); (b) Pd(PPh3)2Cl2, CuI, piperidine, THF (12a : 92%, 12b: 93%, 17: 66%); (c)
n-Bu4NF, THF (13a : 81%, 13b: 93%); (d) Pd(PPh3)2Cl2, CuI, piperidine, THF, air (14a : 90%, 14b: 96%); (e) TsOH, methanol, THF (15a :
87%, 15b: 71%); (f) spin label 4, DCC, DMAP, THF (2a : 78%, 2b: 48%).
acetone,37 trimethylsilylethyne,35 and allyl bromide38 have
been used as additional reagents. Intuitively more obvi-
ous reagents that have been used in addition to Pd
complexes and CuI are iodine36 and oxygen.33,34 We found
that stirring a solution of the protected monophenols 13,
Pd(PPh3)2Cl2 (ca. 2 mol %) and CuI (ca. 4 mol %) in THF
and piperidine under air resulted in a quantitative and
well-defined dimerization giving the protected diphenols
14. As early as a few minutes after addition of the
catalysts, the highly fluorescent protected diphenol 14
could be detected. This suggests that the dimerization
reaction is a fast reaction. Therefore, the butadiynes
found as byproducts of alkynyl-aryl coupling reactions
are most probably, at least partially formed upon the
workup which is carried out under air.39
Treatment of protected diphenols 14 with toluene-
sulfonic acid in the presence of methanol gave the
diphenols 15.
For the star-shaped triradical 3 (Scheme 3), the
protected monophenol 13a was coupled with 1,3,5-tri-
iodobenzene. The product 18 was easily separated from
the accompanying protected diphenol 14a by column
chromatography because of their distinctly different
polarity. The triphenol 19 was obtained through treat-
ment of 18 with toluenesulfonic acid in the presence of
methanol.
The last step in the preparation of the EPR probes is
the attachment of the spin label 4 to the diphenols 8 and
15 and to the triphenol 19 (Schemes 1-3). Attachment
via the acid chloride of 413,19 gave incomplete substitution.
Almost quantitative40 derivatization was achieved through
reaction of the diphenols with a large excess of acid 4 in
(37) Gosper, J . J .; Ali, M. J . Chem. Soc., Chem. Commun. 1994, 1707.
Rossi, R.; Carpita, A.; Bigelli, C. Tetrahedron Lett. 1985, 26, 523.
(38) Vlassa, M.; Ciocan-Tarta, I.; Ma˜rgineanu, F.; Oprean, I. Tet-
rahedron 1996, 52, 1337.
(40) Based on TLC and FD-MS spectra. The intensity of the FD-
MS signals corresponding to 8 or 15 and the corresponding monoes-
terification products was 1-2% of the signal intensity of 1 and 2.
(39) Heitz, W. Pure Appl. Chem. 1995, 67, 1951.

7578 J . Org. Chem., Vol. 65, No. 22, 2000
Godt et al.
Sch em e 3a
NO-C bond. The methyl transfer seems to be a rather
efficient process under the conditions of FD-MS. For
example, in a mass spectrum of 2a signals for M+, [M -
15]+, [M - 30]+, and [M + 15]+ were found with
intensities of 100%, 19%, 5%, and 8%, respectively.
Occasionally signals of low intensity for [M - 45]+ and
[M + 30]+ were detected. The former is assigned to [M -
2CH3 - NO]+ and the latter to [M + 2CH3]+.
From the shortest diradical 1 single crystals were
obtained. X-ray structure analysis42 (Supporting Infor-
mation) reveals a nearly coplanar arrangement of the
three phenylene rings (torsion angles of 4° and 6°). The
planes of the pyrroline and the phenylene rings are
roughly perpendicular to each other (torsion angles of
76-109°). The carbonyl group and the N-O bond are
approximately coplanar with the pyrroline ring as has
been found in other derivatives of spin label 4.43 The
carbonyl group and the double bond in the pyrroline ring
adopt an s-trans conformation. The two pyrroline moi-
eties are transoidally arranged, representing the con-
former with the largest distance between the unpaired
electrons (dN1-N1 ) 2.78 nm, dO1-O1 ) 3.01 nm). In
solution a shorter distance is expected because of a
44
rotation around the bond Caryl-Cethynylene and deviation
from the s-cis conformation of the ester moiety. Never-
theless, despite this conformational flexibility the dis-
tances between the unpaired electrons are rather nar-
rowly distributed as shown by force field calculations and
a Monte Carlo conformational search.12 With the longer
compounds 2 this uncertainty becomes insignificant in
comparison to the experimental error.12
a
Key: (a) Pd(PPh3)2Cl2, CuI, piperidine, THF (87%); (b) TsOH,
methanol, THF (89%); (c) spin label 4, DCC, DMAP, THF (84%).
In conclusion, we have developed a convenient route
to rod-shaped diphenols 8 and 15a ,b based on phenyle-
neethynylene as the building blocks and Pd-Cu cata-
lyzed alkynyl-aryl and alkynyl-alkynyl coupling chem-
istry. Extension of this strategy gave the star-shaped
triphenol 19. These compounds were used for the prepa-
ration of the diradicals 1, 2a ,b and the triradical 3 with
distances of 2.8-5.2 nm between the unpaired electrons.
Minor changes of the discussed synthetic routes will allow
for the preparation of oligoPPEs with only one spin label
and either a terminal aryl or alkynyl unit. Such com-
pounds may be of interest as shape anisotropic and shape
persistent spin probes. Furthermore, these compounds
will enable a combination of spin- and fluorescence45
labeling of biomolecules with the additional advantage
of a rigidly attached spin label.5 As shown with the
synthesis of the spinlabeled compounds 1, 2a ,b, and 3,
the corresponding phenols 8, 15a ,b, and 19 are easily
derivatized and can therefore be used as photolumines-
cent modules for the preparation of, e.g., photolumines-
cent rod-coil blockcopolymers46 and polymer additives.47
the presence of dicyclohexylcarbodiimide and DMAP. The
products were identified by NMR spectroscopy and field
desorption mass spectrometry (FD-MS).
Mass spectrometry is of special value because the
1
signals in H NMR spectra are broad and signals result-
ing from the spin label moiety were not detected. Usually,
the most intense signal in the FD-MS spectra corresponds
to M+. Additional, significant signals, besides the signals
that are due to dicationic spezies, correspond to [M -
15]+, [M - 30]+, and [M + 15]+. Their intensity relative
to the signal intensity of M+ varied considerably. For
example, in two FD-MS spectra of diradical 2b the signal
of [M - 15]+ was found to reach 14% and 40% of the
intensity of the M+ signal, respectively. Loss of one
methyl group, i.e., a signal for [M - 15]+ is commonly
found for N-oxyl radicals with methyl groups at the
R-position to the nitrogen atom under the conditions of
electron impact or chemical ionization mass spectrom-
etry.41 The signals [M -30]+ in the spectra of diradicals
1 and 2 and triradical 3 are assigned to the loss of two
methyl groups, one per spin label and not to the loss of
NO. This interpretation is based on the finding that the
Mm+-signals of the monoesterification products of diphe-
nols 8 and 15 are accompanied by signals corresponding
to [Mm - 15]+ and [Mm + 15]+ but not by [Mm - 30]+.
The signals corresponding to [M + 15]+ are assigned to
diradicals which have added a methyl group, most
probably by radical recombination of 1, 2 or 3 with an in
situ formed methyl radical and thus formation of an
Exp er im en ta l Section
Gen er a l Meth od s. The reactions were performed under
argon unless otherwise described. Solutions for coupling
(42) The crystallographic data have been deposited with the Cam-
bridge Crystallographic Data Centre as supplementary publication no.
CCDC-146143. A Copy of the data can be obtained free of charge on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (Fax:
(+44) 1223-336-033. E-mail: deposit@ccdc.cam.ac.uk).
(43) Wiley, D. W.; Calabrese, J . C.; Harlow, R. L.; Miller, J . S. Angew.
Chem. 1991, 103, 459. Wiley, D. W.; Calabrese, J . C.; Miller, J . S. J .
Chem. Soc., Chem. Commun. 1989, 1523.
(44) The rotation barrier was calculated to be ca. 1 kcal/mol:
Seminario, J . M.; Zacarias, A. G.; Tour, J . M. J . Am. Chem. Soc. 1998,
120, 3970.
(45) Crisp, G. T.; Gore, J . Tetrahedron 1997, 53, 1523. Davies, M.
J .; Shah, A.; Bruce, I. J . Chem. Soc. Rev. 2000, 29, 97.
(41) Davies, A. P.; Morrison, A.; Barratt, M. D. Org. Mass. Spectrom.
1974, 8, 43. Morrison, A.; Davies, A. P. Org. Mass. Spectrom. 1970, 3,
353. Sosnovsky, G.; Rao, N. U. M.; Li, S. W.; Swartz, H. M. J . Org.
Chem. 1989, 54, 3667.

Synthesis of EPR Probes
J . Org. Chem., Vol. 65, No. 22, 2000 7579
reactions were carefully degassed through several freeze-
pump-thaw cycles. THF was distilled from sodium/benzophe-
none. The petroleum ether used had a boiling range of 30-40
°C. For flash chromatography, Merck silica gel (40-63 µm)
was used. Thin-layer chromatography (TLC) was carried out
on silica gel coated aluminum foils (Merck, 60F254). Unless
otherwise specified, NMR spectra were recorded at room
temperature in CD2Cl2 as solvent and internal standard on a
300 MHz instrument. For signal assignment the carbon
multiplicity was determined by a DEPT-135 experiment. The
UV/vis and fluorescence spectra were recorded in CH2Cl2. The
melting points were determined in open capillaries. The
starting compounds 1-iodo-4-(tetrahydropyran-2-yloxy)benzene
(11),48 [4-(tetrahydropyran-2-yloxy)phenyl]ethyne (5),48 1,4-
dihexyl-2,5-diiodobenzene (6),20 and the alkynes 10a ,b20 were
prepared as described in the literature. 1-Oxyl-2,2,5,5-tetra-
methylpyrroline-3-carboxylic acid (4) was purchased from
Acros.
mg, 1.40 mmol) in THF (6 mL) was added N,N′-dicyclohexyl-
carbodiimide (258 mg, 1.25 mmol). The reaction mixture was
stirred at room temperature for 20 h. The precipitate was
filtered off and washed with diethyl ether and THF until the
solid was colorless. The yellow filtrate was washed with 2 N
HCl and subsequently with brine. The solution was dried
(MgSO4) and concentrated in vacuo. Flash chromatography
(petroleum ether/diethyl ether 1:2 v/v; Rf ) 0.52; The crude
product was dissolved in a small amount of warm CH2Cl2 and
applied in this form to the column.50) gave diradical 1 (256
mg, 76%) as a yellow solid tenaciously including methylene
chloride which had been used for the transfer of the material.
An intensely yellow colored compound of unidentified structure
was eluted first (Rf ) 0.83). Crystals for X-ray analysis were
obtained by recrystallization in ethanol containing a small
amount of ethyl acetate. Mp (from ethanol/ethyl acetate):
176.7-178.0 °C. 1H NMR: all signals are broad and struc-
tureless δ 7.63 (4 H), 7.42 (2 H), 7.21 (very broad, 4 H), 2.86
(4 H), 1.74 (4 H), 1.38 (15 H), 0.92 (6 H). 13C NMR: δ 148.4
(broad; CAr-O), 141.8 (CAr-Hex), 132.0 and 131.7 (CArH), 121.8
(CAr-CtC), 121.6 (CH ortho to OH), 120.7 (CAr-CtC), 92.3 and
87.9 (CtC), 33.4, 31.1, 30.0, 28.5, and 22.0 (CH2), 13.2 (CH3).
UV/vis: λmax [nm] (ꢀ [106 cm2 mol-1]) ) 314 (46.9; shoulder),
332 (59.4), 350 (43.0; shoulder). Emission (λexcitation ) 320
nm): λ ) 366, 385 nm (maximum). Anal. Calcd for C52H62N2O6
(811.076) (recrystallized from ethanol/ethyl acetate): C, 77.00;
H, 7.71; N, 3.45. Found: C, 77.17; H, 7.68; N, 3.64. FD-MS:
m/z ) 826.3 (20%, [M + CH3]+), 811.2 (100%, M+), 796.2 (20%,
[M - CH3]+), 645.0 (3%, M+ of monoesterification product),
405.8 (23, M2+).
P r otected Dip h en ol 7. To a solution of diiodo compound
6 (2.00 g, 4.01 mmol) and protected monophenol 5 (1.62 g, 8.01
mmol) in diethylamine (30 mL) were added Pd(PPh3)2Cl2 (56
mg, 0.08 mmol) and CuI (30 mg, 0.16 mmol). After the reaction
mixture was stirred overnight at room temperature, the
solvent was removed under reduced pressure. The residue was
dissolved in diethyl ether and water and the aqueous phase
was extracted with diethyl ether. The combined organic phases
were washed with saturated aqueous NH4Cl, dried (Na2SO4)
and concentrated in vacuo. Flash chromatography (petroleum
ether/CH2Cl2 2:1 v/v; Rf ) 0.10) gave 7 as an offwhite solid
(1.9 g, 74%). Mp: 141.5-142.8 °C. 1H NMR: δ 7.46 (half of
AA′XX′, 4 H, H meta to OTHP), 7.35 (s, 2 H, C6H2), 7.05 (half
of AA′XX′, 4 H, H ortho to OTHP), 5.45 (t, J ) 3.2 Hz, 2 H,
O2CH), 3.87 and 3.62 (2 m, 2 H each, OCH2), 2.81 (m, 4 H,
ArCH2), 2.1-1.2 (m, 28 H, CH2), 0.88 (t, J ) 7.0 Hz, 6 H, CH3).
13C NMR: δ 157.8 (CAr-O), 142.5 (CAr-Hex), 133.1 (CH meta
to OTHP), 132.5 (CH of C6H2), 123.0 (CAr-CtC of C6H2), 117.0
(CH ortho to OTHP), 116.8 (CAr-CtC of C6H4), 96.9 (O2CH),
94.3 and 87.6 (CtC), 62.5 (OCH2), 34.5, 32.2, 31.1, 30.7, 29.7,
25.6, 23.1 and 19.2 (CH2), 14.3 (CH3). Anal. Calcd for C44H54O4
(646.912): C, 81.69; H, 8.41. Found: C, 81.68; H, 8.51.
Dip h en ol 8. To a solution of 7 (900 mg, 1.39 mmol) in meth-
anol (30 mL) and THF (40 mL) was added p-toluenesulfonic
acid monohydrate (27 mg, 0.14 mmol). After 4 h at room temp-
erature, the reaction mixture was cooled with an ice bath, and
water was added. The product was extracted into diethyl ether.
The combined organic phases were washed with brine, dried
(Na2SO4) and concentrated in vacuo. Flash chromatography
(petroleum ether/ diethyl ether 1:1 v/v; Rf ) 0.26) gave 8 (563
Mon ofu n ction a lized OligoP P E 12a . To a solution of
alkyne 10a (863 mg, 1.91 mmol) and 1-iodo-4-(tetrahydropy-
ran-2-yloxy)benzene (11) (529 mg, 1.74 mmol) in THF (15 mL)
and piperidine (5 mL) were added PdCl2(PPh3)2 (13 mg, 0.02
mmol) and CuI (7 mg, 0.04 mmol) at room temperature. The
reaction was stirred at room temperature for 21 h. The
suspension was cooled (ice bath), and diethyl ether and water
were added. The aqueous phase was extracted with diethyl
ether. The combined organic phases were washed successively
with water, saturated aqueous NH4Cl, water, and brine and
dried (Na2SO4). The solvent was removed in vacuo. Flash
chromatography (petroleum ether/CH2Cl2 2:1 v/v, Rf ) 0.62)
gave 12a (1.0 g, 92%) as a pale yellow oil. 1H NMR: δ 7.45
(half of AA′XX′, 2 H, H meta to OTHP), 7.32 and 7.30 (2 s, 1
H each, C6H2) 7.04 (half of AA′XX′, 2 H, H ortho to OTHP),
5.44 (t, J ) 3.2 Hz, 1 H, O2CH), 3.87 and 3.59 (2 m, 1 H each,
OCH2), 2.77 (m, 4 H, ArCH2), 2.1-1.2 (m, 22 H, CH2), 1.16 (s,
21 H, CH(CH3)2), 0.89 (m, 6 H, CH3). 13C NMR: δ 157.8 (CAr
-
1
mg, 85%) as an offwhite solid. Mp: 159.2-159.9 °C. H NMR
O), 143.1 and 142.5 (CAr-Hex), 133.3 (CH of C6H2), 133.2 (CH
meta to OTHP), 132.4 (CH of C6H2), 123.4 and 122.9 (CAr-Ct
C of C6H2), 117.0 (CH ortho to OTHP), 116.8 (CAr-CtC of
C6H4), 106.2 (CtC-TIPS), 96.9 (O2CH), 95.6 (CtC-TIPS), 94.4,
and 87.5 (ArCtCAr), 62.6 (OCH2), 34.8, 34.5, 32.3, 32.2, 31.3,
31.2, 30.7, 29.8, 29.7, 25.6, 23.1, and 19.2 (CH2), 18.9 (CH-
(CH3)2), 14.2 (CH2CH3), 11.9 (SiCH). Anal. Calcd for C42H62O2-
Si (627.042): C, 80.45; H, 9.97. Found: C, 80.29; H, 9.91.
(CDCl3): δ 7.41 (half of AA′XX′, 4 H, H meta to OH), 7.32 (s,
2 H, C6H2), 6.81 (half of AA′XX′, 4 H, H ortho to OH), 4.84 (s,
2 H, OH), 2.77 (m, 4 H, ArCH2), 1.67 (m, 4 H, CH2), 1.5-1.2
(m, 12 H, CH2), 0.87 (t, J ) 7.0 Hz, 6 H, CH3). 13C NMR
(CDCl3): δ 155.6 (CAr-O), 142.0 (CAr-Hex), 133.1 (CH meta to
OH), 132.1 (CH of C6H2), 122.5 (CAr-CtC of C6H2), 116.1 (CAr
-
CtC of C6H4), 115.5 (CH ortho to OH), 93.6 and 87.2 (CtC),
34.1, 31.8, 30.6, 29.2 and 22.6 (CH2), 14.1 (CH3). UV/vis: λmax
[nm] (ꢀ [106 cm2 mol-1]) ) 313 (38.7; shoulder), 333 (55.9), 352
(40.5; shoulder). Emission (λexcitation ) 330 nm): λ ) 363
(maximum), 382 nm. Anal. Calcd for C34H38O2 (478.676): C,
85.31; H, 8.00. Found: C, 84.00; H, 8.22. FD-MS: m/z ) 956.5
(6%, [2M]+), 478.1 (100%, M+), 239.1 (24%, M2+).
Com p ou n d 17. To a solution of protected monophenol 5
(2.72 g, 13.5 mmol) and iodo compound 16 (5.00 g, 11.7 mmol)
in piperidine (20 mL) and THF (160 mL) were added PdCl2-
(PPh3)2 (86 mg, 0.12 mmol) and CuI (44 mg, 0.23 mmol) at
room temperature. The reaction mixture was stirred overnight.
Aqueous workup as described for 12a followed by flash
chromatography (petroleum ether/CH2Cl2 1:1 v/v; Rf ) 0.09)
gave 17 (3.9 g, 66%) as a slightly beige colored solid. Mp: 65.5-
66.5 °C. 1H NMR: δ 7.45 (half of AA′XX′, 2 H, H meta to
OTHP), 7.32 and 7.27 (2 s, 1 H each, C6H2), 7.04 (half of
AA′XX′, 2 H, H ortho to OTHP), 5.44 (t, J ) 3.2 Hz, 1 H, O2-
CH), 4.51 (br s, 2 H, CH2OH), 3.87 and 3.59 (2 m, 1 H each,
Dir a d ica l 1.49 To a cooled (ice bath) solution of 8 (200 mg,
0.42 mmol), spin label 4 (230 mg, 1.25 mmol), and DMAP (171
(46) E.g.: Kukula, H.; Ziener, U.; Scho¨ps, M.; Godt, A. Macromol-
ecules 1998, 31, 5160. Benfaremo, N.; Sandman, D. J .; Tripathy, S.;
Kumar, J .; Yang, K.; Rubner, M. F.; Lyons, C. Macromolecules 1998,
31, 3595. Francke, V.; Ra¨der, H. J .; Geerts, Y.; Mu¨llen, K. Macromol.
Rapid Commun. 1998, 19, 275. Tew, G. N.; Li, L.; Stupp, S. I. J . Am.
Chem. Soc. 1998, 120, 5601. J enekhe, S., A.; Chen, X. L. Science 1999,
283, 372.
(47) Palmans, A. R. A.; Eglin, M.; Montali, A.; Weder, C.; Smith, P.
Chem. Mater. 2000, 12, 472.
(48) Godt, A. J . Org. Chem. 1997, 62, 7471.
(50) The diradicals were found to be labile when adsorbed onto silica
gel. E.g., preparation of 1 as described, however applying the crude
product adsorbed on silica gel (This freely flowing powder was obtained
by dissolving the compound in CH2Cl2, adding some silica gel to this
solution, and removing the solvent in vacuo) to a silica gel column
resulted in a yield of only 12%.
(49) This is an improved procedure in comparison to the one given
in ref 13.

7580 J . Org. Chem., Vol. 65, No. 22, 2000
Godt et al.
CH2CH2O), 2.74 (m, 4 H, ArCH2), 2.1-1.2 (m, 22 H, CH2), 0.89
(m, 6 H, CH3). - 13C NMR: δ ) 157.8 (CAr-O), 142.8 and 142.5
(CAr-Hex), 133.2 (CH meta to OTHP), 132.9 and 132.4 (CH of
C6H2), 123.5 and 122.1 (CAr-CtC of C6H2), 117.0 (CH ortho to
OTHP), 116.7 (CAr-CtC of C6H4), 96.9 (O2CH), 94.4, 92.3, 87.4
and 84.5 (CtC), 62.6 (CH2CH2O), 52.0 (CH2OH) 34.5, 34.2,
32.2, 32.1, 31.0, 30.9, 30.7, 29.6, 29.5, 25.6, 23.05, 23.03 and
19.2 (CH2), 14.3 (CH3). Anal. Calcd for C34H44O3 (500.723): C,
81.56; H, 8.86. Found: C, 81.63; H, 8.87.
P r otected Mon op h en ol 13a fr om 17. To a solution of 17
(3.88 g, 7.75 mmol) in diethyl ether (150 mL) were added a
mixture of MnO2 (10.8 g, 31 mmol) and powdered KOH (0.87
g, 15.5 mmol) in four portions over a period of 4 h.51 The
reaction was monitored by TLC (petroleum ether/diethyl ether
6:1 v/v, Rf(17) ) 0.08, Rf(13a ) ) 0.49). Filtration over silica
gel with diethyl ether as solvent gave 13a (3.5 g, 94%) as a
colorless solid.
crystallization in ethanol (30 mL for 1.37 g of 15a ) gave
analytically pure 15a as a pale yellow solid. Mp: 119.3-121.4
°C. 1H NMR: δ 7.43 (half of AA′XX′, 4 H, H meta to OH), 7.37
and 7.34 (2 s, 2 H each, C6H2), 6.85 (half of AA′XX′, 4 H, H
ortho to OH), 5.21 (s, 2 H, OH), 2.78 (m, 8 H, ArCH2), 1.68 (m,
8 H, CH2), 1.36 (m, 24 H, CH2), 0.89 (m, 12 H, CH3). 13C NMR:
δ 156.5 (CAr-O), 144.2 and 142.6 (CAr-Hex), 133.64 (CH of C6H2),
133.57 (CH meta to OH), 132.5 (CH of C6H2), 124.3 (CAr-Ct
C-CtC), 121.1 (CAr-CtCAr of C6H2), 116.0 (CH ortho to OH;
Most probably this signal covers up the signal of C-CtC of
C6H4), 95.0 and 87.2 (ArCtCAr), 82.1 (CtC-CtC), 78.5 (Ct
C-CtC), 34.4, 34.3, 32.2, 32.1, 31.0, 30.9, 29.6, 29.5, and 23.0
(CH2), 14.29 and 14.25 (CH3). UV/vis: λmax [nm] (ꢀ [106 cm2
mol-1]) ) 338 (54.2; shoulder), 357 (83.1), 385 (62.2). Emission
(λexcitation ) 360 nm): λ ) 403 (maximum), 427 nm. Anal. Calcd
for C56H66O2 (771.142): C, 87.22; H, 8.63. Found: C, 87.17;
H, 8.68.
Dir a d ica l 2a . The procedure for the preparation of diradical
1 was followed, however with a reaction time of 3 d. The
reaction of 15a (300 mg, 0.39 mmol) with spin label 4 (215
mg, 1.17 mmol) in the presence of N,N′-dicyclohexylcarbodi-
imide (241 mg, 1.17 mmol) and DMAP (157 mg, 1.29 mmol)
in THF (7 mL) gave after flash chromatography (petroleum
ether/diethyl ether 1:1 v/v; Rf ) 0.32)50 diradical 2a (335 mg,
P r otected Mon op h en ol 13a fr om 12a . To a solution of
12a (825 mg, 1.32 mmol) in THF (30 mL) was added 1 M n-Bu4-
NF (2.6 mL, 2.6 mmol) in THF at room temperature. After
1.5 h, diethyl ether and then water was added. The aqueous
phase was extracted with diethyl ether. The combined organic
phases were washed with brine, dried (MgSO4) and concen-
trated in vacuo. Recrystallization of the residual solid in
methanol (40 mL) gave 13a as a colorless solid (501 mg, 81%).
1
78%) as a yellow solid. Mp: 164.0-164.8 °C. H NMR: δ 7.61
(br s, 4 H, H meta to OR), 7.40 (s, 4 H, C6H2), 7.24 (very broad,
4 H, H ortho to OR), 2.80 (m, 8 H, ArCH2), 1.69 (br s, 8 H,
CH2), 1.6-1.2 (m, 24 H, CH2), 0.89 (m, 12 H, CH3). 13C NMR:
δ 148.8 (CAr-O), 143.4 and 142.0 (CAr-Hex), 132.9, 133.2, 131.9
(CArH), 122.9 (CAr-CtC), 121.8 (broad, CH ortho to OR), 120.8
(CAr-CtC; This signal splits into two when the compound is
measured in CDCl3), 93.2 and 88.0 (ArCtCAr), 81.2 (CtC-
CtC), 77.8 (CtC-CtC), 33.6, 33.5, 31.3, 31.24, 31.20, 30.1,
28.7, 28.6, and 22.2 (CH2), 13.5 (CH3). UV/vis: λmax [nm] (ꢀ
[106 cm2 mol-1]) ) 286 (31.8), 338 (66.1; shoulder), 354 (91.7),
383 (64.9). Emission (λexcitation ) 355 nm): λ ) 399 (maximum),
423 nm. Anal. Calcd for C74H90N2O6 (1103.542): C, 80.54; H,
8.22; N, 2.54. Found: C, 80.50; H, 8.26; N, 2.46. FD-MS: m/z
) 1118.1 (7%, [M + CH3]+), 1103.1 (100%, M+), 1088.1 (19%,
[M - CH3]+), 1073.6 (6%, [M - 2CH3]+), 938.0 (1%, M+ of
monoesterification product), 559.1 (3%, [M + CH3]2+), 551.5
(17%, M2+).
1
Mp: 58.3-59.6 °C. H NMR: δ 7.45 (half of AA′XX′, 2 H, H
meta to OTHP), 7.33 and 7.32 (2 s, 1 H each, C6H2), 7.04 (half
of AA′XX′, 2 H, H ortho to OTHP), 5.44 (t, J ) 3.1 Hz, 1 H,
O2CH), 3.86 and 3.59 (2 m, 1 H each, OCH2), 3.35 (s, 1 H,
C∞CH), 2.76 (m, 4 H, ArCH2), 2.1-1.2 (m, 22 H, CH2), 0.89
(m, 6 H, CH3). 13C NMR: δ 157.8 (CAr-O), 143.3 and 142.5 (CAr
-
Hex), 133.4 (CH of C6H2), 133.2 (CH meta to OTHP), 132.4
(CH of C6H2), 123.9 and 121.5 (CAr-CtC of C6H2), 117.0 (CH
ortho to OTHP), 116.7 (CAr-CtC of C6H4), 96.9 (O2CH), 94.5,
87.3, 82.8, 81.7 (CtC), 62.5 (OCH2), 34.5, 34.2, 32.2, 32.1, 31.0,
30.9, 30.7, 29.6, 29.5, 25.6, 23.05, 23.02 and 19.2 (CH2), 14.3
(CH3). Anal. Calcd for C33H42O2 (470.697): C, 84.21; H, 8.99.
Found: C, 84.29; H, 9.01.
P r otected Dip h en ol 14a . To a solution of 13a (500 mg,
1.06 mmol) in THF (19 mL) and piperidine (4.7 mL) were
added PdCl2(PPh3)2 (11 mg, 0.02 mmol) and CuI (7 mg, 0.04
mmol) at room temperature. The reaction mixture was stirred
under air for 3.5 h. The reaction was monitored by TLC
(petroleum ether/diethyl ether 5:1 v/v, Rf(14a ) ) 0.41, Rf(13a )
) 0.59). Dichloromethane and then water were added. The
aqueous phase was extracted with CH2Cl2. The combined
organic phases were washed with saturated aqueous NH4Cl
and dried (MgSO4). The solvent was removed in vacuo.
Filtration over silica gel (CH2Cl2; Rf ) 0.69) gave 14a (451 mg,
Mon ofu n ction a lized OligoP P E 12b. To a solution of 10b
(2.25 g, 3.13 mmol) and 1-iodo-4-(tetrahydropyran-2-yloxy)-
benzene (11) (864 mg, 2.84 mmol) in THF (25 mL) and
piperidine (8 mL) were added PdCl2(PPh3)2 (20 mg, 0.03 mmol)
and CuI (11 mg, 0.06 mmol) at 0 °C. The reaction mixture was
stirred for 6 h at room temperature. Aqueous workup as
described for 12a followed by flash chromatography (petroleum
ether/CH2Cl2 4:1 v/v; Rf ) 0.41) gave 12b (2.4 g, 93%) as a
1
90%) as an offwhite solid. Mp: 136.7-137.7 °C. H NMR: δ
1
pale yellow oil. H NMR: δ 7.46 (half of AA′XX′, 2 H, H meta
7.46 (half of AA′XX′, 4 H, H meta to OTHP), 7.37 and 7.35 (2
s, 2 H each, C6H2), 7.05 (half of AA′XX′, 4 H, H ortho to OTHP),
5.45 (t, J ) 3.1 Hz, 2 H, O2CH), 3.87 and 3.60 (2 m, 2 H each,
OCH2), 2.78 (m, 8 H, ArCH2), 2.1-1.2 (m, 44 H, CH2), 0.90
(m, 12 H, CH3). 13C NMR: δ 157.9 (CAr-O), 143.2 and 142.6
(CAr-Hex), 133.6 (CH of C6H2), 133.2 (CH meta to OTHP), 132.5
(CH of C6H2), 124.4 (C-CtC-CtC), 121.1 (CAr-CtCAr of
C6H2), 117.0 (CH ortho to OTHP), 116.6 (CAr-CtC of C6H4),
96.9 (O2CH), 95.2 and 87.4 (ArCtCAr), 82.1 (CtC-CtC), 78.5
(CtC-CtC), 62.5 (OCH2), 34.5, 34.4, 32.2, 32.1, 31.0, 30.9,
30.7, 29.6, 29.5, 25.6, 23.0, and 19.2 (CH2), 14.3 (CH3). Anal.
Calcd for C66H82O4(939.378): C, 84.39; H, 8.80. Found: C,
84.46; H, 8.88.
to OTHP), 7.36 (s, 2 H, C6H2), 7.34 and 7.32 (2 s, 1 H each,
C6H2), 7.05 (half of AA′XX′, 2 H, H ortho to OTHP), 5.45 (t, J
) 3.1 Hz, 1 H, O2CH), 3.87 and 3.60 (2 m, 1 H each, OCH2),
2.80 (m, 8 H, ArCH2), 2.1-1.2(m, 38 H, CH2), 1.16 (s, 21 H,
CH(CH3)2), 0.88 (m, 12 H, CH2CH3). 13C NMR: δ 157.8 (CAr
-
O), 143.1, 142.6, 142.44 and 142.36 (CAr-Hex), 133.3 (CH of
C6H2), 133.2 (CH meta to OTHP), 132.82, 132.77 and 132.5
(CH of C6H2), 123.4, 123.3, 123.2 and 122.9 (CAr-CtC of C6H2),
117.0 (CH ortho to OTHP), 116.8 (CAr-CtC of C6H4), 106.2 (Ct
C-TIPS), 96.9 (O2CH), 95.8 (CtC-TIPS), 94.5, 93.4, 93.2, and
87.6 (ArCtCAr), 62.6 (OCH2), 34.8, 34.6, 32.3, 32.2, 31.3, 31.2,
31.14, 31.08, 30.7, 29.8, 29.72, 29.68, 25.6, 23.1, 19.2 (CH2),
18.9 (CH(CH3)2), 14.3 (CH2CH3), 11.9 (SiCH). Anal. Calcd for
Dip h en ol 15a . The procedure for the preparation of diphe-
nol 8 was followed. The reaction of protected diphenol 14a (2.94
g, 3.13 mmol) with toluenesulfonic acid monohydrate (720 mg,
3.8 mmol) in THF (340 mL) and methanol (130 mL) gave after
flash chromatography (CH2Cl2, Rf ) 0.21) diphenol 15a (2.1
g, 87%) as a pale yellow solid containing tetrahydropyran-2-
yl-methyl ether (ca. 7 mol %).52 This product was used without
further purification for the preparation of diradical 2a . Re-
C
62H90O2Si (895.486): C, 83.16; H, 10.13. Found: C, 83.25; H,
10.12.
P r otected Mon op h en ol 13b. To a solution of 12b (2.10 g,
2.35 mmol) in THF (40 mL) was added 1 M n-Bu4NF (4.5 mL,
4.5 mmol) in THF at room temperature. The reaction mixture
turned instantaneously dark red. After 3 h, diethyl ether and
subsequently water were added. The aqueous phase was
extracted with diethyl ether. The combined organic phases
(52) Characteristic 1H NMR signals of tetrahydropyran-2-yl-methyl
ether: δ (CDCl3) ) 4.52 (t, 1H), 3.86 (m, 1H), 3.53 (m, 1H), 3.40 (s,
3H).
(51) If the reaction is not complete, more MnO2/KOH is added: see
description in ref 20.

Synthesis of EPR Probes
J . Org. Chem., Vol. 65, No. 22, 2000 7581
were washed with brine and dried (MgSO4). The solvent was
removed in vacuo. The residual, slightly red oil turned violet
by storing overnight at room temperature in vacuo. To this
violet oil was added methanol (10 mL). The methanol solution
was removed from the oil with a pipet. Dissolving the residue
again in methanol (30 mL) under heating gave, upon cooling
to room temperature, 13b as a violet solid (1.6 g, 93%). Mp:
401 (99.1). Emission (λexcitation ) 375 nm): λ ) 419 (maximum),
446 nm. Anal. Calcd for C96H122O2(1308.030): C, 88.15; H, 9.40.
Found: C, 87.51; H, 9.46. FD-MS: m/z ) 1308.9 (65%, M+),
811.1 (7%), 654.6 (100%, M2+).
Dir a d ica l 2b. The procedure for the preparation of diradical
1 was followed, however with a reaction time of 29 h. The
reaction of 15b (150 mg, 0.115 mmol) with spin label 4 (63
mg, 0.34 mmol) in the presence of N,N′-dicyclohexylcarbodi-
imide (71 mg, 0.34 mmol) and DMAP (46 mg, 0.38 mmol) in
THF (4 mL) gave after flash chromatography (petroleum ether/
diethyl ether 1:1 v/v; Rf ) 0.40; The crude material had been
adsorbed onto silica gel prior to chromatography50) diradical
2b (91 mg, 48%) as a yellow solid. An intensively yellow colored
compound of unidentified structure (20 mg) was eluted first.
1
43.4-43.6 °C. H NMR: δ 7.46 (half of AA′XX′, 2 H, H meta
to OTHP), 7.37 (s, 2 H, C6H2), 7.36 and 7.34 (2 s, 1 H each,
C6H2), 7.05 (half of AA′XX′, 2 H, H ortho to OTHP), 5.45 (t, J
) 3.1 Hz, 1 H, O2CH), 3.87 and 3.60 (2 m, 1 H each, OCH2),
3.37 (s, 1 H, CtCH), 2.80 (m, 8 H, ArCH2), 2.1-1.2 (m, 38 H,
CH2), 0.89 (m, 12 H, CH3). 13C NMR: δ 157.8 (CAr-O), 143.3,
142.6, 142.5 and 142.4 (CAr-Hex), 133.4 (CH of C6H2), 133.2
(CH meta to OTHP), 132.84, 132.77 and 132.5 (CH of C6H2),
123.8, 123.5, 122.8 and 121.8 (CAr-CtC of C6H2), 117.0 (CH
ortho to OTHP), 116.8 (CAr-CtC of C6H4), 96.9 (O2CH), 94.5,
93.5, 93.0, and 87.5 (ArCtCAr), 82.7 and 81.9 (CtCH), 62.6
(OCH2), 34.6, 34.5, 34.2, 32.3, 32.24, 32.21, 32.1, 31.14, 31.08,
30.9, 30.7, 29.7, 29.6, 29.5, 25.6, 23.1, 23.0, 19.2 (CH2), 14.3
(CH3). Anal. Calcd for C53H70O2 (739.141): C, 86.12; H, 9.55.
Found: C, 86.13; H, 9.53.
1
Mp: 148.0-148.7 °C. H NMR: δ 7.61 (br s, 4 H, H meta to
OR), 7.41 (s, 4 H, C6H2), 7.40 and 7.39 (2 s, 2 H each, C6H2),
7.2 (very broad, H ortho to OR), 2.84 (m, 16 H, ArCH2), 1.71
(m, 16 H, CH2), 1.6-1.2 (m, 50 H, CH2), 0.89 (m, 24 H, CH3).
13C NMR: δ 149.0 (CAr-O), 143.7, 142.3, 142.01, 141.98 (CAr
-
Hex), 133.1, 132.5, 132.4, 132.3, and 132.2 (CArH), 123.7, 122.7,
and 122.3 (CAr-CtC), 122.0 (broad, CH ortho to OR), 121.2 and
121.0 (CAr-CtC), 93.5, 92.9, 92.7, and 88.5 (ArCtCAr), 81.6
(CtC-CtC), 78.1 (CtC-CtC), 34.0, 33.9, 33.8, 31.68, 31.67,
31.63, 31.5, 30.6, 30.5, 30.4, 29.1, 29.0, 28.9, 22.51, 22.48 (CH2),
13.8 and 13.7 (CH3). UV/vis: λmax [nm] (ꢀ [106 cm2 mol-1]) )
314 (55.2; shoulder), 380 (144.3), 398 (102.6). Emission (λexcitation
) 370 nm): λ ) 417 (maximum), 443 nm. Anal. Calcd for
P r otected Dip h en ol 14b. To a solution of 13b (900 mg,
1.22 mmol) in THF (20 mL) and piperidine (5 mL) were added
PdCl2(PPh3)2 (13 mg, 0.02 mmol) and CuI (7 mg, 0.04 mmol)
at room temperature. The reaction mixture was stirred under
air for 3 h. The reaction was monitored by TLC (petroleum
ether/diethyl ether 5:1 v/v, Rf(14b) ) 0.48, Rf(13b) ) 0.61).
Diethyl ether and then water were added. Upon standing
overnight a precipitate formed which was dissolved by addition
of THF, diethyl ether, and CH2Cl2 (probably, workup with only
CH2Cl2 is the best choice). The organic phase was washed with
saturated aqueous NH4Cl and brine and dried (MgSO4). The
solvent was removed in vacuo. Filtration over silica gel (CH2-
Cl2; Rf ) 0.84) gave 14b (863 mg, 96%) as an intensely yellow
colored solid. Mp: 120.7-121.6 °C. 1H NMR: δ 7.46 (half of
AA′XX′, 4 H, H meta to OTHP), 7.40 and 7.38 (2 s, 2 H each,
C6H2), 7.37 (s, 4 H, C6H2), 7.05 (half of AA′XX′, 4 H, H ortho
to OTHP), 5.45 (t, J ) 3.1 Hz, 2 H, O2CH), 3.88 and 3.60 (2 m,
2 H each, OCH2), 2.81 (m, 16 H, ArCH2), 2.1-1.2 (m, 76 H,
CH2), 0.89 (m, 24 H, CH3). 13C NMR: δ 157.8 (CAr-O), 144.3,
142.6, and 142.5 (CAr-Hex), 133.7 (CH of C6H2), 133.2 (CH meta
to OTHP), 132.9 and 132.5 (CH of C6H2), 124.3 (CAr-CtC-Ct
C), 123.6, 122.7, and 121.5 (CAr-CtCAr of C6H2), 117.0 (CH
ortho to OTHP), 116.7 (C-CtC of C6H4), 96.9 (O2CH), 94.6,
94.3, 93.0, and 87.5 (ArCtCAr), 82.2 (CtC-CtC), 78.6 (Ct
C-CtC), 62.6 (OCH2), 34.6, 34.4, 32.2, 32.1, 31.1, 30.7, 29.7,
29.5, 25.6, 23.1, 19.2 (CH2), 14.3 (CH3). Anal. Calcd for
C
114H146O6N2 (1640.430): C, 83.47; H, 8.97, N 1.71. Found: C,
83.26; H, 9.12, N 1.58. FD-MS: m/z ) 1655 (7, [M + CH3]+),
1640.01 (100%, M+), 1625.1 (13%, [M - CH3]+), 1610 (3%, [M
- 2CH3]+), 1473.9 (1%, M+ of monoesterification product),
827.6 (7%), 820.1 (51%, M2+), 812.6 (16%, [M - 2CH3]2+).
1,3,5-Tr iiod oben zen e.53,54 A suspension of 1,3,5-tribro-
mobenzene (6.00 g, 19 mmol), potassium iodide (142 g, 0.86
mol), and CuI (54 g, 0.28 mol) in 1,3-dimethyl-1,3-diazacyclo-
hexane (180 mL) was heated to 155 °C for 24.5 h. After being
cooled to room temperature, the brown, viscous reaction
mixture was poured into water (800 mL). The precipitate was
isolated, washed well with water, and dried (P4O10, vacuum).
The obtained solid contained 1,3,5-triiodobenzene, 1,3-diiodo-
benzene and 1-bromo-3,5-diiodobenzene in a ratio of 11:6:1 (1H
NMR spectroscopically determined). Extraction in a Soxhlet
apparatus with diethyl ether (400 mL) and concentration of
the turbid solution to a volume of ca. 100 mL gave a colorless
solid which was recrystallized from ethanol (350 mL) to give
1,3,5-triiodobenzene (2.9 g, 33%) as colorless needles contami-
nated with ca. 2 mol % of 1-bromo-3,5-diiodobenzene (deter-
mined with 1H NMR spectroscopy).
C
106H138O4 (1476.266): C, 86.24; H, 9.42. Found: C, 86.55; H,
9.54.
Dip h en ol 15b. The procedure for the preparation of diphe-
P r otected Tr ip h en ol 18. To a solution of 13a (400 mg,
0.85 mmol) and 1,3,5-triiodobenzene (124 mg, 0.27 mmol) in
THF (9 mL) and piperidine (4 mL) were added PdCl2(PPh3)2
(6 mg, 0.09 mmol) and CuI (3 mg, 0.04 mmol) at 0 °C. The
reaction mixture was stirred for 6.5 h at room temperature.
Aqueous workup as described for 12a followed by flash
chromatography (petroleum ether/CH2Cl2 10:8 f 1:2 v/v, Rf
(petroleum ether/CH2Cl2 10:8) ) 0.37) gave 18 (350 mg, 87%)
as a yellow-green fluorescent, very viscous oil. 1H NMR: δ 7.64
(s, 3 H, C6H3), 7.46 (half of AA′XX′, 6 H, H meta to OTHP),
7.40 and 7.38 (2 s, 3 H each, C6H2), 7.05 (half of AA′XX′, 6 H,
H ortho to OTHP), 5.45 (t, J ) 3.1 Hz, 3 H, O2CH), 3.87 and
3.60 (2 m, 3 H each, OCH2), 2.83 (m, 12 H, ArCH2), 2.1-1.2
(m, 66 H, CH2), 0.89 (m, 18 H, CH3).
nol 8 was followed, however with a longer reaction time of 19
h. The reaction was monitored by TLC (CH2Cl2; Rf(15b) ) 0.12,
Rf(14b) ) 0.84). The reaction of 14b (749 mg, 0.51 mmol) with
toluenesulfonic acid monohydrate (20 mg, 0.11 mmol) in THF
(40 mL) and methanol (15 mL) gave after flash chromatogra-
phy (petroleum ether/diethyl ether 1:2 v/v; Rf ) 0.48) diphenol
15b (578 mg, 87%) containing tetrahydropyran-2-ylmethyl
ether (ca. 3 mol %).52 The latter was removed by recrystalli-
zation in ethanol (7 mL) giving 15b (473 mg, 71%) as an
intensely yellow solid. Most probably, chromatography can be
omitted because tetrahydropyran-2-yl-methyl ether is the only
1
other product of the reaction. Mp: 157.7-159.0 °C. H NMR:
Tr ip h en ol 19. The procedure for the preparation of diol 8
was followed, however with a reaction time of 5 h. The reaction
of protected triphenol 18 (340 mg, 0.23 mmol) with toluene-
sulfonic acid monohydrate (10 mg, 0.05 mmol) in THF (11 mL)
and methanol (10 mL) gave after chromatography on silica gel
δ 7.43 (half of AA′XX′, 4 H, H meta to OH), 7.40, 7.38, 7.37,
and 7.36 (4 s, 2 H each, C6H2), 6.85 (half of AA′XX′, 4 H, H
ortho to OH), 5.20 (br s, 2H, OH), 2.81 (m, 16 H, ArCH2), 1.70
(m, 16 H, CH2), 1.34 (m, 48 H, CH2), 0.88 (m, 24 H, CH3). 13C
NMR: δ 156.5 (CAr-O), 144.2, 142.6, 142.5 (CAr-Hex), 133.7 (CH
of C6H2), 133.5 (CH meta to OH), 132.8, and 132.5 (CH of
C6H2), 124.3 (CAr-CtC-CtC), 123.5, 122.7 and 121.4 (CAr-Ct
CAr of C6H2), 116.1 (CAr-CtC of C6H4), 116.0 (CH ortho to OH),
94.4, 94.2, 93.0, and 87.4 (ArCtCAr), 82.2 (CtC-CtC), 78.6
(CtC-CtC), 34.52, 34.48, 34.36, 32.24, 32.19, 32.08, 31.13,
30.06, 30.99, 29.7, 29.5, 23.1, (CH2), 14.3 (CH3). UV/vis: λmax
[nm] (ꢀ [106 cm2 mol-1]) ) 314 (38.1; shoulder), 382 (139.4),
(53) In analogy to bromine-iodine exchange described by Suzuki,
H.; Kondo, A.; Ogawa, T. Chem. Lett. 1985, 411. However, 1,3-dimethyl-
1,3-diazacyclohexane was used instead of HMPA.
(54) Similar preparation: Scho¨berl, U.; Magnera, T. F.; Harrison,
R. M.; Fleischer, F.; Pflug, J . L.; Schwab, P. F. H.; Meng, X.; Lipiak,
D.; Noll, B. C.; Allured, V. S.; Rudalevige, T.; Lee, S.; Michl, J . J . Am.
Chem. Soc. 1997, 119, 3907.

7582 J . Org. Chem., Vol. 65, No. 22, 2000
Godt et al.
plates using a chromatotron (petroleum ether/diethyl ether 1:3,
Rf ) 0.35; the compound was applied as a solution in diethyl
ether) triphenol 19 (250 mg, 89%) as a pale yellow solid. Mp:
compound, 21 mg, Rf ) 0.87) was eluted first. Mp: 152.6-
1
153.6 °C. H NMR: all signals are broad and structureless, δ
7.69 (3 H, C6H3), 7.64 (6 H, H meta to OR), 7.45 (6 H, C6H2),
7.23 (very broad, 6 H, H ortho to OR), 2.88 (12 H, ArCH2),
1.76 (12 H, ArCH2), 1.40 (36 H, CH2), 3.6 (18 H, CH3). 13C
NMR: δ 148.7 (CAr-O), 142.2 and 142.0 (CAr-Hex), 133.2, 132.2,
132.1, 131.9 (C6H2, C6H3, CH meta to OR), 123.9 (CAr-CtC of
C6H3), 122.4 (CAr-CtC), 121.8 (CH ortho to OR), 121.7, 120.9
(CAr-CtC), 92.7, 91.8, 89.2, and 88.1 (CtC), 33.7, 31.3, 30.2,
28.8, 22.2 (CH2), 13.51, 13.46 (CH3). Anal. Calcd for C117H138N3O9
(1730.403): C, 81.21; H, 8.04, N 2.43. Found: C, 81.20; H, 7.99,
N 2.46. FD-MS: m/z ) 1750.1 (8%, [M + CH3]+), 1734.8 (100%,
M+), 1719.6 (3%, [M - CH3]+), 1704.1 (3%, [M - 2CH3]+), 868.6
(10%, M2+).
1
145.8-146.9 °C. H NMR: δ 7.65 (s, 3 H, C6H3), 7.44 (half of
AA′XX′, 6 H, H meta to OH), 7.40 and 7.38 (2 s, 3 H each,
C6H2), 6.85 (half of AA′XX′, 6 H, H ortho to OH), 5.24 (br s, 3
H, OH), 2.83 (m, 12 H, ArCH2), 1.72 (m, 12 H, ArCH2), 1.37
(m, 36 H, CH2), 0.89 (m, 18 H, CH3). 13C NMR: δ 156.5 (CAr
-
O), 143.0 and 142.6 (CAr-Hex), 134.0 (CH of C6H3), 133.6 (CH
meta to OH), 132.9 and 132.6 (CH of C6H2), 124.9 (CAr-CtC
of C6H3), 123.8 and 122.1 (CAr-CtC of C6H2), 116.1 (CAr-CtC
of C6H4), 116.0 (CH ortho to OH), 94.5, 92.5, 90.2, and 87.3
(ArCtCAr), 34.5, 32.22, 32.20, 31.13, 31.0, 29.65, 29.63, 23.09,
and 23.06 (CH2), 14.33 and 14.27 (CH3). Anal. Calcd for
C90H102O3 (1231.803): C, 87.75; H, 8.35. Found: C, 87.21; H,
8.34. FD-MS: m/z ) 1231.8 (100%, M+), 615.9 (44%, M2+).
Sta r sh a p ed Tr ir a d ica l 3. The procedure for the prepara-
tion of diradical 1 was followed, however with a reaction time
of 17 h. The reaction of 19 (150 mg, 0.12 mmol) with spin label
4 (101 mg, 0.55 mmol) in the presence of N,N′-dicyclohexyl-
carbodiimide (113 mg, 0.55 mmol) and DMAP (74 mg, 0.61
mmol) in THF (10 mL) gave after flash chromatography
(petroleum ether/diethyl ether 2:1 v/v, Rf ) 0.40; the crude
product was dissolved in a small amount of CH2Cl2 and applied
in this form to the column50) triradical 3 (177 mg, 84%) as a
yellow solid. An intensively yellow fraction (unidentified
Ack n ow led gm en t. We thank J . Thiel for assistance
in the laboratory and for recording the mass spectra and
B. Zimmer for recording the fluorescence spectra.
Su p p or tin g In for m a tion Ava ila ble: Structure of diradi-
cal 1 in the crystal, X-ray crystallographic data, and figures
showing the UV and fluorescence spectra of diphenols 8, 15a ,b
and diradicals 1, 2a ,b. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O005556J