Copper-promoted N-arylations of cyclic imides within six-membered rings: A facile route to arylene-based organic materials

Article abstract of DOI:10.1021/jo0481351

(Chemical Equation Presented) Cyclic imides within six-membered rings are shown to undergo efficient N-arylation using various arylboronic esters mediated by copper(II) acetate in the presence of an amine base and oxygen atmosphere with gentle heating. Until now, the synthesis of N-arylated cyclic imides having six-membered rings was restricted largely to strongly heating anilines in the presence of anhydrides. This reaction is applicable to the synthesis of new organic materials based on arylene imide and bis(imide) dyes, such as perylene-3,4: 9,10-bis(dicarboximide)s.

Full text of DOI:10.1021/jo0481351

these macromolecules are constructed with imide link-
ages, which have a large influence on the photophysical
and conformational properties of the molecules.13,14 How-
ever, an important synthetic challenge is the efficient
formation of imide bonds that connect the various
components of these target molecules under conditions
sufficiently mild to prevent the alteration of other
functional groups within the molecules. N-Aryl imide
bond formation frequently requires the low-yielding
condensation of an arylamine with a free anhydride at
high temperatures for extended periods of time. Ad-
ditional complications can include the air sensitivity of
many amines as well as the insolubility and hydrolytic
susceptibility of the anhydrides. Herein, we report that
cyclic imides and arylboronic esters undergo efficient
N-arylation reactions in the presence of copper(II) ac-
etate.
Copper-Promoted N-Arylations of Cyclic
Imides within Six-Membered Rings: A
Facile Route to Arylene-Based Organic
Materials
Erin T. Chernick, Michael J. Ahrens,
Karl A. Scheidt,* and Michael R. Wasielewski*
Department of Chemistry and Center for Nanofabrication
and Molecular Self-Assembly, Northwestern University,
2145 Sheridan Road, Evanston, Illinois 60208-3113
wasielew@chem.northwestern.edu
Received October 21, 2004
Transition metal-catalyzed cross-coupling reactions
have revolutionized organic synthesis over the last
several decades. There have been a number of recent
advances in the field of transition metal-promoted C-N
cross-coupling reactions, most notably by Buchwald and
Hartwig.15-22 We desired a mild and efficient method to
N-arylate cyclic imides within six-membered rings from
the corresponding free imide and aryl boronic ester.
Although copper-promoted heteroatom coupling reactions
between various amines, amides, thiols, and boronic acids
have been reported,23-37 the use of imides as coupling
Cyclic imides within six-membered rings are shown to
undergo efficient N-arylation using various arylboronic
esters mediated by copper(II) acetate in the presence of an
amine base and oxygen atmosphere with gentle heating.
Until now, the synthesis of N-arylated cyclic imides having
six-membered rings was restricted largely to strongly heat-
ing anilines in the presence of anhydrides. This reaction is
applicable to the synthesis of new organic materials based
on arylene imide and bis(imide) dyes, such as perylene-3,4:
9,10-bis(dicarboximide)s.
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10.1021/jo0481351 CCC: $30.25 © 2005 American Chemical Society
Published on Web 01/22/2005
1486
J. Org. Chem. 2005, 70, 1486-1489

TABLE 1. Variation of Aryl Coupling Partner
on optimizing the results for the most economical reagent,
copper(II) acetate. All reactions were performed under
an oxygen atmosphere (caution!) utilizing an oxygen
balloon and stirred with 4 Å molecular sieves to prevent
the boronic esters from hydrolyzing. Interestingly, reac-
tions employing pyridine instead of triethylamine as the
base in this reaction afforded poor yields of the desired
compounds. In addition, reactions in ambient air also
resulted in lower yields overall.
Although phenylboronic acids have recently been dem-
onstrated to be active coupling partners with select five-
membered ring cyclic imides, such as succinimide and
phthalimide,26,29,37,38 we desired a general method ap-
plicable to naphthalimides because they are an important
structural analogue to the aromatic dyes we employ in
efforts to prepare photofunctional organic materials. We
thought that the use of arylboronic esters would be
especially appealing since these compounds are generally
stable,easytohandleandpurify,andsimpletosynthesize.39-44
Additionally, previous reports have suggested that it is
not the boronic acid, but the cyclic boroxine, which is the
reactive coupling species.45 Accordingly, various arylbo-
ron species were assessed for their coupling propensity
(Table 1). Reaction conditions were optimized utilizing
HPLC and an external standard to calculate yields for
this survey; however, isolated yields were not obtained
until favorable conditions were applied to a variety of
imide substrates and extended aromatic systems dis-
cussed later in this paper. The coupling of the arylboronic
ester derived from 1,3-propanediol (1c) generated the
desired imide 3 in 94% yield (entry 3), while the ethylene
glycolate afforded a satisfactory 71% yield of 3. However,
the phenyl boron catecholate (1d) gave a disappointing
32% yield of 3, possibly due to decomposition of the
boronic ester upon addition of the copper(II) acetate.45
Surprisingly, the phenyl boron pinacolate (1e) does not
react with naphthalimide, even upon heating (entry 5).
This is consistent with previous reports of low yields
when the boronic ester is coupled with a phenol, amine,
and cyclic amide,45 presumably due to steric hindrance
around the boron. However, we do obtain a 43% yield of
imide 4 when the electron-deficient boronic ester 1f is
reacted with naphthalimide (2c), suggesting that elec-
tronic factors as well as steric interactions are important
(entry 6).
a All reactions were carried out for approximately 20 h with the
exception of entry 1, which was reacted for 44 h. b Yields are
obtained via HPLC using 3 as an external standard. c Isolated
yield via column chromatography.
partners in these processes is rare and has been re-
stricted to cyclic imides within five-membered rings.26,29,37,38
The general reaction conditions were optimized utiliz-
ing naphthalimide (2c) as the imide and varying the aryl
boron species (Table 1). Gratifyingly, moderate to excel-
lent yields are obtained when 1 equiv of imide, 2-3 equiv
of boronic ester, 2-3 equiv of copper(II) acetate, and 3
equiv of triethylamine are employed in methylene chlo-
ride with moderate heating. Various copper sources in
addition to copper(II) acetate were explored in this
reaction including copper(II) fluoride, copper(II) chloride,
and copper(II) triflate (not shown). Both the chloride and
fluoride salts were ineffective, yielding little to no prod-
uct. Copper(II) triflate promoted the desired reaction
(43% yield of imide 3), but the need to use stoichiometric
quantities of Cu(II) in this reaction focused our attention
With an efficient N-arylation system for cyclic imide 3
in hand, we decided to expand the scope of this reaction
by exploring a variety of imide substrates (Table 2). Since
the 1,3-propanediol-derived phenylboronic ester (1c)
provided optimal yields in Table 1, we decided to utilize
this boronic ester under standard conditions in these
experiments. The reaction proceeds with both maleimide
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J. Org. Chem, Vol. 70, No. 4, 2005 1487

TABLE 2. Survey of Imide Substrates
SCHEME 1. Construction of a Stacking Porphyrin
Precursor
study that successfully undergo N-arylation, we conclude
that the scope of this reaction may be limited to cyclic
imides.
Last, we have employed this chemistry to prepare a
precursor useful for the synthesis of photofunctional
chromophoric arrays.6 This is accomplished by coupling
perylenebis(imide) 2d with 4-formylphenylboronic ester
9 shown in Scheme 1. Synthesis of this precursor via the
traditional route of coupling an anhydride with arylamine
would require protection of the aldehyde to avoid imine
formation by self-condensation or the condensation of
p-aminobenzyl alcohol with the anhydride, followed by
oxidization of the alcohol to the aldehyde. Another
drawback includes the difficult recovery of the perylene
monoimide-monoanhydride due to hydrolysis. By utiliz-
ing the copper(II)-mediated coupling reaction, aldehyde
10 is obtained in good yield (73%). An added benefit of
the gentle copper-promoted conditions is any unreacted
bis(imide) 2d that does not undergo coupling can be
completely recovered and reused in subsequent reactions.
Employing Lindsey’s conditions for porphyrin synthesis,46
the treatment of aldehyde 10 with pyrrole and trifluo-
roacetic acid, followed by oxidation with p-chloranil yields
porphyrin 11 in a respectable 23% yield. Conditions
previously used in our laboratory to synthesize porphy-
rins analogous to 11 are harsh, requiring several days
of reflux in pyridine to promote imide condensation of
5,10,15,20-tetrakis(p-aminophenyl)porphyrin with an ex-
cess of perylene monoimide-monoanhydride (PIA).47
a Standard reaction conditions involve a 1:3:3:3 ratio of imide/
ester/Cu/base stirred in CH2Cl2 for 19-20 h at 45 °C. Yields are
obtained via column chromatography. b 1:3:2:3 ratio of imide/ester/
Cu/base stirred at 55 °C. c R ) 3,5-di-tert-butylphenyl. d Reaction
stirred for 48 h at 40 °C in CHCl3.
(entry 1, 43% yield) and phthalimide (entry 2, 97% yield),
with the lower yield of 2a accompanied by significant
amounts of side products. Six-membered cyclic imides
afford good yields of the desired N-arylated products
(entries 3 and 4), even when accompanied with extended
π-systems. Interestingly, the cyclic imides are necessary
for this reaction to proceed. For example, no reaction is
observed when dibenzamide (2e) is employed (entry 5).
It is possible that under the reaction conditions, imide
2e chelates the copper(II) metal center, since its carbonyl
groups can adopt a parallel, coplanar conformation
similar to an acetylacetonate ligand. Chelation of the
copper may prevent the active copper species from
participating in the reaction and/or may attenuate the
reactivity of the imide. Since this conformation is un-
available to the cyclic imide coupling partners in this
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1488 J. Org. Chem., Vol. 70, No. 4, 2005

In conclusion, we have developed a mild and efficient
method to couple cyclic imides with arylboronic esters
using copper(II) acetate, which is cost-effective and easy
to handle without the need for an inert atmosphere. The
overall process avoids thermal condensation of anhy-
drides and arylamines at high temperatures, thereby
accessing the desired functionalized imides in much
higher yields with much less degradation of the starting
materials. Further applications of this N-arylation meth-
odology toward the construction of large chromophoric
arrays as well as studies to render the reaction catalytic
in copper(II) are ongoing and will be reported in due
course.
Acknowledgment. We would like to thank Steven
Mullen and Richard Milberg from the mass spectrom-
etry laboratory at University of Illinois at Urbana-
Champaign for HR FAB measurements. This work was
supported by the Division of Chemical Sciences, Office
of Basic Energy Sciences, U.S. Department of Energy
under grant no. DE-FG02-99ER14999 (M.R.W.). We
would also like to thank the Natural Sciences and
Engineering Research Council of Canada (NSERC) for
a post-graduate research scholarship supplied to E.T.C.
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Supporting Information Available: Compounds 1b-f,
2e, 3-6, and 9 have previously been reported.6,47-54 Com-
pounds 1a and 2a-c are commercially available. General
experimental details and spectroscopic data for compounds 2d,
7, 10, and 11. This material is available free of charge via the
Internet at http://pubs.acs.org.
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