Synthesis of heterocyclic monomers via Reissert chemistry

Article abstract of DOI:10.1002/pola.24172

The chemistry of Reissert compounds has been used to synthesize activated difluorotetraketone monomers containing two coupled isoquinolyl moieties, linked at either the 1,1'-or 4,4'-positions. These monomers offer routes to novel families of poly(heteroarylene ether)s. New 4,4'-coupled bis(Reissert compound) 9 containing 4,4'-diketo moieties failed to afford the desired difluorotetraketo monomer upon attempted rearrangement. However, analogous bis(Reissert compound) 19 containing 4,4'-dibenzyl units did so, via aldehyde condensation, hydrolysis of the intermediate ester and oxidation of the four benzylic moieties to keto groups; thus the novel difluorotetraketone monomer 10 was prepared. Novel bis(Reissert compound)s 24, 28, and 35 were synthesized from diacid chlorides and 4-(pfluorobenzyl)isoquinoline. Rearrangement of 24 to the diketone 29, followed by oxidation of the 4-benzyl moieties resulted in difluorotetraketone monomer 30 containing a 1,1'-linked bisisoquinoline. The 1,1'-linked bis(isoquinolylfluorodiketo) monomer 38, isomeric with 10, was prepared from 4-(p-fluorobenzyl) Reissert compound 36 by condensation with terephthaldehyde, ester hydrolysis to diol 37, and oxidation. In the course of this effort, a number of new isoquinoline Reissert compounds were synthesized as model systems.

Full text of DOI:10.1002/pola.24172

Synthesis of Heterocyclic Monomers via Reissert Chemistry
HARRY W. GIBSON, KIMBERLY K. BRUMFIELD, ROGER A. GRISLE,* CHRISTINE K. F. HERMANNy
Department of Chemistry, Virginia Polytechnic Institute & State University, Blacksburg, Virginia 24061-0212
Received 22 April 2010; accepted 4 June 2010
DOI: 10.1002/pola.24172
Published online in Wiley InterScience (www.interscience.wiley.com).
ABSTRACT: The chemistry of Reissert compounds has been used
to synthesize activated difluorotetraketone monomers contain-
ing two coupled isoquinolyl moieties, linked at either the 1,10- or
4,40-positions. These monomers offer routes to novel families of
poly(heteroarylene ether)s. New 4,40-coupled bis(Reissert com-
pound) 9 containing 4,40-diketo moieties failed to afford the
desired difluorotetraketo monomer upon attempted rearrange-
ment. However, analogous bis(Reissert compound) 19 contain-
ing 4,40-dibenzyl units did so, via aldehyde condensation,
hydrolysis of the intermediate ester and oxidation of the four
benzylic moieties to keto groups; thus the novel difluorotetrake-
tone monomer 10 was prepared. Novel bis(Reissert compound)s
24, 28, and 35 were synthesized from diacid chlorides and 4-(p-
fluorobenzyl)isoquinoline. Rearrangement of 24 to the diketone
29, followed by oxidation of the 4-benzyl moieties resulted in
difluorotetraketone monomer 30 containing a 1,10-linked bisiso-
quinoline. The 1,10-linked bis(isoquinolylfluorodiketo) monomer
38, isomeric with 10, was prepared from 4-(p-fluorobenzyl) Reis-
sert compound 36 by condensation with terephthaldehyde, ester
hydrolysis to diol 37, and oxidation. In the course of this effort, a
number of new isoquinoline Reissert compounds were synthe-
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sized as model systems. 2010 Wiley Periodicals, Inc. J Polym
Sci Part A: Polym Chem 48: 3856–3867, 2010
KEYWORDS: fluoroketone monomer; heteroatom-containing
polymers; high performance polymers; isoquinoline; poly(ary-
lene ether); poly(ether ketone)s; reissert compound
INTRODUCTION
was found that the process proceeds efficiently and much
more conveniently at room temperature using sodium
hydride and dimethylformamide (DMF).6(c,d) The esters 2
can be hydrolyzed by base to give secondary alcohols 3
(Scheme 1). On the other hand, using 50% sodium hydrox-
ide/acetonitrile for the aldehyde reaction yields a mixture of
the ester (2) and alcohol (3) in many cases.7 However, it has
been shown that the base/solvent combination and the reac-
tion time and temperature dictate which product will be
obtained. Shorter reaction times and lower temperatures
favor formation of the ester.8
Reissert Compounds
Reissert compounds, a-(acylamino)nitriles, are a very inter-
esting class of compounds that were discovered in 1905 by
Arnold Reissert.1 They are formed by the formal addition of
an acyl cyanide across a carbon–nitrogen double bond. Vari-
ous nitrogen heterocycles, such as pyridine, quinoline, benz-
imidazole, and phenanthridine produce these derivatives.2
The most studied cases are the isoquinoline Reissert com-
pounds, 1 (Scheme 1).
Several methods have been developed for the preparation of
Reissert compounds. These include use of aqueous media
(Schotten-Baumann conditions: acid chloride and KCN),1 sin-
gle phase nonaqueous media [acid chloride with HCN in ben-
zene3; trimethylsilyl cyanide (TMSCN) in methylene chloride
or dimethylformamide4], and a two phase method (methyl-
ene chloride-water, acid chloride, KCN).5
Exposure of the anion to an alkyl halide results in formation
of the 1-alkyl derivative 4, which upon basic hydrolysis
forms the 1-alkylisoquinoline (5) through rearomatization
(Scheme 2).2,9,10 In the absence of an electrophile, an intra-
molecular rearrangement converts the Reissert anion into
ketone 6 via a tricylic aziridine intermediate (Scheme 3).2,9
Gibson found that the ability of the Reissert compound to
undergo rearrangement versus alkylation depends on the
nature of the acyl group.10
Reissert compounds possess an acidic proton alpha to the
cyano group that dictates the chemistry of these compounds.
It can easily be abstracted to form the anion with a variety
of base/solvent combinations.2 Reissert anions undergo reac-
tions with aldehydes via an intramolecular rearrangement
driven by rearomatization to form esters 2; initially this pro-
cess was carried out at low temperature in ether-dioxane
with phenyllithium as the base,2,6(a,b) but subsequently it
Nitrogen Containing Polymers
Nitrogen-containing polymers are a special class of materials
that exhibit very useful features which can be attributed to
(1) the basicity of the nitrogen atom(s), (2) hydrogen bond-
ing 7 of N-H moieties, and (3) quaternization. Polyamides,
*Present address: 3M Corporation, 3M Center, Bldg. 230-1D-15, St. Paul, MN 55144-1000.
†Present address: Department of Chemistry and Physics, Box 6949, Radford University, Radford, VA 24142.
Correspondence to: H. W. Gibson (E-mail: hwgibson@vt.edu)
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Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 48, 3856–3867 (2010) 2010 Wiley Periodicals, Inc.
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SCHEME 1 Formation of an iso-
quinoline Reissert compound 1
and reaction of its anion with an
aldehyde to produce ester 2 and
by hydrolysis alcohol 3.
such as nylon-6,6 and KelvarTM, possess remarkable strength
due to hydrogen bonding between the carbonyl groups and
the NAH moieties and find applications in fibers and plas-
tics.11(a) Aliphatic polyimides also possess valuable mechani-
cal properties combined with dielectric features that make
them useful in micro- and opto-electronics.11(b,c) Quaternary
salt forms are highly polar, ionic polymers that are used as
anion exchange resins, coatings, adhesives, ion conductors,
and in water treatment and coagulation.12 Aromatic nitro-
gen-containing polymers exhibit enhanced thermo-oxidative
stability and good mechanical performance.13 This class
includes the (1) polyimides,11(d) (2) polyquinoxalines, (3)
polyquinolines, (4) polybenzimidazoles, (5) polybenzothia-
zoles, and (6) polybenzoxazoles. At elevated temperatures,
these polymers retain useful mechanical properties for long
periods of time.
derived from isoquinoline with aldehydes.15 Guilani et al.
applied this method to produce a family of novel 4,40-
coupled bis(isoquinoline)s in good yields by reacting isoqui-
noline with dialdehydes.16 They also developed a method for
the oxidation of the 4-methylene unit of the resultant bis(iso-
quinoline)s to the corresponding diketones.16
Bis(isoquinoline Reissert compound)s Derived from
Diacid Chlorides
Earlier attempts toward the synthesis of bis(Reissert com-
pound)s using diacid chlorides used the two-phase method,
but generally resulted in less than 10% yields, the best yield
obtained being 22%.17 The low yields resulted from the hy-
drolysis of the diacid chlorides by water prior to the forma-
tion of the bis(Reissert compounds).
Gibson et al. prepared bis(Reissert compound)s using the
single phase TMSCN method in yields ranging from 77 to
100%.18,19 These bis(Reissert compound)s derived from
monoacid chlorides with bisisoquinolines and diacid chlor-
ides with monoisoquinolines constitute a novel class of AA
monomers, which along with AB analogs were used in the
step-growth syntheses of heterocyclic polymers20 analogous
to the processes used to make small molecules 3 and 4, that
is, through alkylation with dialdehydes or dihaloalkanes. Ali-
phatic acylaminonitriles, ‘‘aliphatic Reissert compounds,’’2(e)
were also used as monomers for preparation of poly(Reissert
compound)s.21 In related work bis(aminonitrile)s were ary-
lated with difluorodiphenyl sulfone to afford novel poly(ke-
tone ketone sulfone)s upon hydrolysis.22
Poly(ether ketone)s
Poly(ether ketone)s are a class of polymers which have
attracted considerable attention as a direct result of their
extremely high thermal and chemical stabilities and good
mechanical properties.14 Poly(ether ketone)s are usually
crystalline and therefore are resistant to solvent attack, mak-
ing them ideal for aerospace applications. The only common
room temperature solvent known for poly(ether ketone) or
poly(ether ether ketone) is concentrated sulfuric acid. Typi-
ꢀ
cal poly(ether ketone)s have Tgs ranging from 100 to 200 C
ꢀ
and Tms ranging from 300 to >400 C. They exhibit excellent
thermo-oxidative stability, withstanding processing tempera-
ture as high as 400 ꢀC and can be used at temperatures
>200 ꢀC. In addition, they are stiff, tough, resist wear, and
possess low flammability.
Using Reissert compound chemistry we also reported an iso-
quinoline functionalized as a monomer for incorporation into
poly(arylene ether)s.18(b)23 The monomer, l,4-bis(p-fluoro-
benzoyl)isoquinoline, was condensed with a number of
bisphenols, producing a family of novel poly(1,4-isoquino-
linediyl ether ketone)s. These materials were amorphous
(Tgs ranging from 180 to 210 ꢀC), in contrast to PEEK, and
Bis(isoquinoline Reissert Compound)s from 4,4-Coupled
Bis(isoquinolines)
Minter and Re reported a facile synthesis of 4-substituted
isoquinolines by reaction of boron-activated enamines
SCHEME 2 Alkylation of an isoquinoline Reissert compound 1
and hydrolysis of the resultant 4 to the 1-alkylisoquinoline 5.
SCHEME 3 Rearrangement of the anion of an isoquinoline
Reissert compound 1 to a 1-acylisoquinoline 6.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
SCHEME 4 Conversion of bisiso-
quinoline 7 to diketo derivative 8
and thence to bis(Reissert com-
pound) 9, rearrangement of
which was anticipated to form
difluorotetraketo monomer 10.
exhibited excellent thermal stability due to the presence of
the heterocyclic moiety.
a shift of H3 and H4 protons downfield into the aromatic
region, confirming that rearrangement instead of displace-
ment of the fluoride occurred (Scheme 5).
RESULTS AND DISCUSSION
With elimination of this possible side reaction, the final step
in the synthesis of the tetraketone monomer 10 was rear-
rangement of the diketo bis(Reissert compound) 9 by reac-
tion with NaH in DMF at room temperature (Scheme 4). The
reaction afforded a black solid, of which less than 50% was
soluble in CDCl3; some black particles remained insoluble.
Therefore, the rearrangement was attempted at 0 ꢀC, but
again the CDCl3 insoluble black particles, more than 1/2 the
sample, were also present. No well defined product was iso-
lated, although it did appear from 1H NMR that the desired
product 10 was produced. In an attempt to optimize the
reaction, model systems were examined.
The overall thrust of the research summarized here was to
use Reissert chemistry to incorporate isoquinoline moieties
into monomers for step-growth polymerizations, specifically
activated fluoroketone monomers containing 1,10- and 4,40-
coupled isoquinolines. Preliminary polymerization results are
also reported.
Monomers from 4,40-Coupled Bisisoquinolines
The primary target of this part of our studies was the tetra-
ketone monomer 10 (Scheme 4). Isoquinoline was reacted
with terephthaldehyde in the presence of sodium triethylbor-
ohydride to yield the known16 p-bis(4-isoquinolyl)xylene (7)
in 84% yield.
The first model system investigated was one in which there
was a carbonyl moiety at the 4-position (Scheme 6). 4-Ben-
zylisoquinoline (13)15 was refluxed in MnO2/benzene, giving
4-benzoylisoquinoline (14). The ketone 14 was reacted with
p-fluorobenzoyl chloride in the presence of TMSCN and a
catalytic amount of AlCl3. The new Reissert compound 15
was obtained in 94% yield. Attempted rearrangement of
Reissert compound 15 to the corresponding new diketone
16 with NaH in DMF yielded only 33% of a crude product,
whose TLC indicated the presence of seven spots, none pre-
Tetraketo Monomer from 4,40-Diketo Bisisoquinoline
Reissert Compounds
We first considered an approach in which the benzylic moi-
eties of the bisisoquinoline are oxidized before other struc-
tural elaboration (Scheme 4). Bisisoquinoline 716 was
refluxed with MnO2/benzene to afford the desired, previ-
ously unknown diketo product 8 in 72% yield.
The diketone 8 was reacted with p-fluorobenzoyl chloride in
the presence of TMSCN and a catalytic amount of AlCl3. The
desired product, Reissert compound 9, was obtained in 89%
yield. Initially, there were some reservations regarding this
reaction, since TMSCN is known to react with carbonyls to
form cyanohydrins.18(a),24 However, this reaction led to no
formation of cyanohydrin or cyanohydrin ester.
1
senting itself in great abundance. The H NMR spectrum was
complicated, confirming a mixture of products. When the
solid was dissolved in CDCl3, insoluble black particles were
noticed as was the case of the rearrangement product of
In the case of an N-(p-fluorobenzoyl) Reissert compound
such as 9, the anion might displace the activated fluoride of
the N-acyl moiety, causing polymerization instead of rear-
rangement. This led to the investigation of the rearrange-
ment of a model compound. 2-(p-Fluorobenzoyl)-1,2-dihy-
droisoquinaldonitrile (11)25 was reacted with NaH/DMF to
l
obtain the rearranged product 12 in 90% yield. Its H NMR
spectrum demonstrated complete loss of the H1 proton and
SCHEME 5 Rearrangement of Reissert compound 11 to ketone 12.
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ARTICLE
SCHEME 6 Preparation of Reis-
sert compound 15 and its rear-
rangement to ketone 16.
bis(Reissert compound) 9. It was suspected that the forma-
tion of this side product(s) was occurring due to an electron
transfer process brought about by the 4-carbonyl moiety.
yield the diol 21 in 79% yield. Complete hydrolysis of the
diester was confirmed by the FTIR spectrum. Reaction of
Reissert compound 19 with p-flurobenzaldehyde in 50%
NaOH/MeCN also produced diol 21 directly in 73% yield.
This hypothesis led to the investigation of the rearrangement
of 2-(p-fluorobenzoyl)-4-benzyl-1,2-dihydroisoquinaldonitrile
(17). If an electron transfer process involving the carbonyl
moiety was indeed occurring, then the benzylic analog might
rearrange smoothly. 4-Benzylisoquinoline (13)15 was reacted
with p-fluorobenzoyl chloride via the two phase method
using KCN as a cyanide source; new Reissert compound 17
was obtained in 83% yield (Scheme 7). Reissert compound
17 was then reacted with NaH in DMF, affording 79% of
rearrangement product 18.
The alcohol 21 was refluxed in MnO2/benzene for 12 h. The
desired tetraketone 10 was isolated in 61% yield and con-
firmed by IR, NMR, and elemental analysis.
1,10-Bisisoquinoline Monomers via Diacid
Chloride-Based Reissert Compounds
One way to obtain difunctional Reissert compounds is
through the use of diacid chlorides to form a bis(Reissert
compound) from a simple isoquinoline. We reported a num-
ber of such bis(Reissert compound) monomers previ-
ously.18,19 One problem associated with some of the mono-
mers prepared earlier was their rigidity. Recall that one of
the requirements for step-growth polymerizations is accessi-
ble reacting groups. The more flexible the monomer, the
more accessible the reacting groups because of better solu-
bility of the product polymer. Therefore, one goal of this
work was to synthesize flexible diacid chlorides from which
flexible bis(Reissert compound) monomers could be
made. Aromatic acids were chosen to maintain good thermal
stability. In line with the overall objectives of this particular
portion of the project, we used this approach to prepare acti-
vated difluoro monomers containing 1,10-coupled isoquino-
lines resulting from rearrangement of the new bis(Reissert
compound)s.
The rearrangement of 17 resulted in the desired product
and no black particles were observed; therefore, we con-
cluded that the presence of the carbonyl group at the 4-posi-
tion results in the formation of side products, possibly via an
electron transfer process.
Tetraketo Monomer from 4,40-Dibenzylic Bisisoquinoline
Reissert Compounds
Therefore, to avoid this problem, the second approach to the
target difluorotetraketone monomer 10 involved maintaining
the benzylic moieties at the 4-position of the isoquinoline
unit until later in the synthetic sequence and using the alde-
hyde condensation (Scheme 1) as a means of introducing the
p-fluorobenzoyl moiety at the 1-position of the isoquinoline
nuclei (Scheme 8). Bisisoquinoline 716 was reacted with o-
toluyl chloride and TMSCN with a catalytic amount of AlCl3
at room temperature, leading to the desired new Reissert
compound 19 in 93% yield. The o-toluyl Reissert compound
was chosen because this substitution on the acyl group
essentially eliminates base catalyzed rearrangement to the
ketone.10
Oxybis(benzoyl) Bis(Reissert Compound)
4,40-Oxybis(benzoyl chloride) (22) was reacted with 4-(p-flu-
orobenzyl)isoquinoline (23) via the single phase method
(TMSCN/CH2Cl2) producing new bis(Reissert compound) 24
in 67–70% yield (Scheme 9).
Sulfonylbis(benzoyl) Bis(Reissert Compound)
Reissert compound 19 was reacted with p-fluorobenzalde-
hyde using NaH/DMF, affording an 83% yield of new diester
20. The diester 20 was refluxed in 50% sodium hydroxide
and acetonitrile in the presence of a small amount of benzyl-
trimethylammonium chloride (phase transfer catalyst) to
Commercially available 4,40-sulfonylbis(methyl benzoate)
(25) was converted to the corresponding known dibenzoic
acid 26 by hydrolysis in 96% yield. The dibenzoic acid was
then converted to the diacid chloride 27 using thionyl chlo-
ride. 4-(p-Fluorobenzyl)isoquinoline (23),23 dibenzoyl
SCHEME 7 Preparation of Reissert com-
pound 17 and successful rearrangement
to ketone 18.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
SCHEME 8 Conversion of bisiso-
quinoline 7 to bis(Reissert com-
pound) 19, its condensation with
p-flurobenzaldehyde to produce
diester 20, which was hydrolyzed
to diol 21, and oxidation of the
latter to tetraketo monomer 10.
chloride 27 and TMSCN were reacted in the preparation of
the new bisReissert compound 28, affording a 53–58% yield
(Scheme 10).
et al.,26 which involved reacting the dipotassium salt of 4-
hydroxybenzoic acid with dichlorodiphenylsulfone, producing
the diacid 33 (72%, Scheme 13), which was partially con-
verted to the methyl ester for characterization. The diacid
chloride 34 was prepared by refluxing the diacid in thionyl
chloride. The bis(Reissert compound) 35 was prepared in
62% yield from diacid chloride 34 and 4-(p-fluorobenzyl)iso-
quinoline (23)23 using the single-phase method (Scheme 13).
Di- and Retra-Ketones from Oxybisbenzoyl(Reissert
Compound) 27
Oxygen linked bis(Reissert compound) 24 was subjected to
treatment with NaH in DMF at room temperature. From
NMR it was quite clear that the reaction had not worked as
the AB-pattern for the benzylic methylene protons was still
present along with the upfield signals for H1 and H3; upon
rearrangement with attendant aromatization the benzylic
methylene protons become equivalent and the signals for H1
and H3 move downfield into the aromatic region. Therefore,
the rearrangement of 24 was repeated using THF/NaH
at reflux. The reaction was continuously monitored by proton
NMR. After 2 days, the compound had completely rearranged,
producing diketone 29 in 86–100% yield (Scheme 11).
1,10-Bisisoquinolines via Dialdehyde Condensation of
Reissert Compounds
Another protocol for coupling isoquinoline nuclei at the 1-
position is the reaction of isoquinoline Reissert compounds
with dialdehydes, producing diester analogs of monoester 2
(Scheme 1). Here, this was verified by reaction of the new 4-
(p-fluorobenzyl)isoquinoline Reissert compound 36, which
was prepared from isoquinoline 23 by the TMSCN method in
quantitative yield (Scheme 14). Reissert compound 36 was
condensed with terephthaldehyde using 50% NaOH, followed
by subsequent basic hydrolysis of the intermediate diester,
to afford the 1,10-linked bisisoquinoline diol 37 in 70% yield.
Treatment of diol 37 with MnO2 in refluxing benzene pro-
duced the tetraketo difluoro monomer 38 (in 45% yield
without exhaustive extraction of the metal oxide).
The final step was oxidation of the remaining 4-benzylic
methylenes using MnO2/benzene16 to produce the new
difluorotetraketone monomer 30 in 57% yield.
Sulfonylbisbenzoyl Diketone from Bis(Reissert
Compound) 28
The diketone 31 was similarly synthesized via rearrange-
ment of bis(Reissert compound) 28, which was dissolved in
THF, treated with 2.2 eq. of NaH and refluxed for 2 days
under nitrogen. The yield of diketone 31 was 76% (Scheme
12). Oxidation to the tetraketone has not been executed, but
is expected to proceed without difficulty.
Preliminary Polymerization of Tetraketone
Monomer 10
In a preliminary experiment, the tetraketone monomer 10
was reacted with bisphenol-A using NMP/toluene as a sol-
vent/azeotroping agent and potassium carbonate as base
(Scheme 15). The reaction mixture was precipitated into
methanol, yielding polymer 39, which possessed an intrinsic
viscosity of 0.16 dL/g (25 ꢀC, CHCl3) and was stable up to
Sulfonylbis(p-phenyleneoxy) Bis(Reissert Compound) 35
The synthesis of a novel sulfone-containing dicarboxyclic
acid used a modification of a route reported by Idage
ꢀ
454 C in air by TGA. GPC (polystyrene standards) indicated
SCHEME 9 Synthesis of bis(Reis-
sert compound) 24.
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ARTICLE
SCHEME 10 Synthesis of bis-
(Reissert compound) 28.
SCHEME 11 Rearrangement of bis(Reissert compound) 24 to diketone 29 and oxidation of the latter to tetraketone 30.
SCHEME 12 Rearrangement of bis(Reissert compound) 28 to diketone 31 and proposed oxidation of the latter to tetraketone 32.
SCHEME 13 Synthesis of bis(Reissert compound) 35.
SCHEME 14 Condensation of bis(Reissert compound) 36 with terephthaldehyde to produce a diester, which was hydrolyzed to diol
37, and oxidation of the latter to tetraketo monomer 38, an isomer of tetraketo monomer 10.
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SCHEME 15 Polymerization of activated
difluorotetraketo monomer 10 with
bis(phenol-A) to form poly(heteroarylene
ether ketone) 39.
ꢀ
Mn ¼ 4.9 kDa and Mw ¼ 7.8 kDa. DSC revealed Tg ¼ 180 C
calcium carbonate prior to use. Sodium hydride was used as
a 60% dispersion in mineral oil as obtained from Aldrich
Chemicals. All other solvents were used as received from the
vendor. Melting points were determined in a Mel-temp II
melting point apparatus and are corrected. All proton NMR
spectra were recorded on a Bruker 270 MHz instrument
using tetramethylsilane as an internal standard; the follow-
ing abbreviations are used: s (singlet), d (doublet), m (mul-
tiplet), t (triplet), ArH (aromatic hydrogen). FTIR spectra
were recorded on a Nicolet MX-I with KBr pellets or films on
salt plates. Thermogravimetric analysis was done on a Per-
kin–Elmer 7700 Thermal Analysis System. Differential scan-
ning calorimetry was performed on a DuPont 2100 Dual-
and no Tm. The viscosity and molecular weight of this poly-
mer can no doubt be improved by optimization of the reac-
tion conditions.
CONCLUSIONS
New bis(Reissert compound)s 9 and 19 were synthesized
from 4,40-bisisoquinolines in good yields. The former Reis-
sert compound based on the 4,40-diketo system failed to
afford the desired difluorotetraketo monomer upon
attempted rearrangement. However, the latter Reissert com-
pound based on the 4,40-dibenzyl structure did ultimately do
so, via aldehyde condensation, hydrolysis of the intermediate
ester and oxidation of four benzylic moieties to keto groups.
In the way the novel 4,40-linked bisisoquinolyl difluorotetra-
ketone monomer 10 was prepared. In the course of this
effort new model Reissert compounds 11, 15, and 17 were
synthesized; investigation of their rearrangements indicated
that the presence of a carbonyl at the 4-position results in
the formation of a side product, possibly via electron trans-
fer, that is detrimental.
ꢀ
Sample at 10 C/min. Gel permeation chromatography (GPC)
was carried out in THF using a Waters 150-C equipped with
RI and viscometric detectors; this instrument provided abso-
lute molecular weights, polydispersity index, and Mark-Hou-
wink constants. Mass spectrometry was performed by the
Midwest Center for Mass Spectroscopy, Lincoln, Nebraska,
with the exception of the ms of compound 18, which was
acquired on an in-house Agilent 6220 Accurate Mass TOF
LC/MS Spectrometer. Intrinsic viscosities were measured in
a Fisher Ubelohde Scientic Viscometer 7300. Elemental anal-
yses were performed by Atlantic Microlab (Norcoss, GA).
Novel bis(Reissert compound)s 24, 28, and 35 were synthe-
sized from diacid chlorides and 4-(p-fluorobenzyl)isoquino-
line. Rearrangement of 24 to the diketone, followed by oxi-
dation of the 4-benzyl moieties resulted in 1,10-linked
bisisoquinolyl difluorotetraketone 30. Rearrangement of the
model N-(p-fluorobenzoyl) Reissert compound 11 rather
than displacement of the fluoride, that is, polymerization,
takes place upon treatment with NaH/DMF.
a,a0-Bis(4-isoquinolyl)-p-xylene (7)
Isoquinoline (10.33 g, 80 mmol) was dissolved in 150 mL of
dry THF. Sodium triethylborohydride was added gradually in
four portions of 20 mL of 1.0 M solution (80 mL, 80 mmol).
The reddish–brown solution was allowed to stir at room
temperature for 30 min under N2, after which terephthalde-
hyde, 5.10 g (38 mmol), was added in one portion. The mix-
ture was cooled to 0 ꢀC and 160 mL of 0.5 N NaOH were
added. Ten minutes later, 80 mL of 30% H2O2 were added
gradually. Stirring was continued for 20 h, at the end of
which time the precipitate was collected and dried: 11.50 g
(84%); reported 74%.16 After two recrystallizations from
4-(p-Fluorobenzyl) Reissert compound 36 was condensed
with terephthaldehyde and the resultant ester hydrolyzed to
form diol 37, which in turn was oxidized to the 1,10-linked
bisisoquinolyl difluorotetraketo monomer 38, which is an
isomer of 10.
EXPERIMENTAL
ethanol/water, the pure product was obtained, mp 190.4–
16
ꢀ
ꢀ
190.7 C (reported 186.5–187.5 C).
General
1H NMR (270 MHz, CDCl3): d 4.33, s, ppm, 4H, CH2; 7.10, s,
4H, ArH; 7.5–8.0, m, 8H, H5–8; 8.38, s, 2H, H3; 9.15, s, 2H, H1.
Dichloromethane was obtained from Fisher Scientific and
dried over molecular sieves before use. N,N-dimethylforma-
mide (DMF) and l-methyl-2-pyrrolidinone (NMP) were dis-
tilled from calcium hydride and tetrahydrofuran (THF) from
sodium/benzophenone prior to use. DMSO (N,N-dimethyl-
sulfoxide) was obtained from Aldrich and was distilled with
p-[Bis(4-isoquinolyl)carbonyl]benzene (8)
A mixture of 7.00 g (19 mmol) of bisisoquinoline 7, 210 mL
of benzene and 70 g of MnO2 was allowed to reflux for 2
3862
INTERSCIENCE.WILEY.COM/JOURNAL/JPOLA

ARTICLE
days with a Dean-Stark trap. The oxides were filtered
through Celite and the Celite was washed with chloroform.
The MnO2 was Soxhlet extracted for 5 days with CHCl3. The
combined extract was dried over MgSO4. The solvent was
removed, yielding a golden solid, 4.72 g (72%), which was
recrystallized three times from toluene:hexanes, mp 248.2–
H4. ELEM. ANAL., Calcd. for C16H10NOF: C 76.49, H 4.01, N
5.57; found C 76.38, H 4.00, N 5.53.
4-Benzoylisoquinoline (14)
4-Benzylisoquinoline (13),15 5.00 g (22.8 mmol), 150 mL of
benzene, and 50 g of MnO2 were allowed to reflux for 2
days using a Dean-Stark trap. The mixture was filtered
through Celite and the Celite was washed with chloroform.
The MnO2 was Soxhlet extracted for 4 days with CHCl3. The
combined extract was dried over MgSO4. The solvent was
removed, producing a viscous yellow oil, 3.54 g (66%),
which was triturated with ethanol and recrystallized three
times from ethyl acetate:hexanes and twice from toluene:-
ꢁ1
ꢀ
249.2 C. FTIR (KBr): 1664.5 cm (C¼¼O).
lH NMR (270 MHz, CDCl3): d 7.70–7.85, m, 4H, H6 and H7;
8.00, s, 4H, phenyl; 8.10, d (J ¼ 8), 2H, H8; 8.25, d (J ¼ 8),
2H, H5; 8.69, s, 2H, H3; 9.42 ppm, s, 2H, H1. EI MS: 388
(Mþ). ELEM. ANAL., Calcd. for C26H16N2O2 ꢂ 1/3 C7H8: C
81.19, H 4.49, N 6.68; found: C 80.77, H 4.47, N 6.68.
ꢁ1
ꢀ
hexanes, mp 77.4–78.7 C. FTIR (KBr): 1657.6 cm (C¼¼O).
p-Bis[4-{1-cyano-2-(p-fluorobenzoyl)-1,2-
dihydroisoquinolyl}carbonyl]benzene (9)
lH NMR (270 MHz, CDCl3): d 7.48–7.53, m, 2H, m to C¼¼O;
7.62–7.81, m, 3H, H6,H7 and p to C¼¼O; 7.87–7.91, m, 2H, o
to C¼¼O; 8.09, d (J ¼ 8), 1H, H5; 8.17, d (J ¼ 8), H8; 8.65, s,
1H, H3; 9.41, s, 1H, H1. ELEM. ANAL., Calcd. for C16H11NO: C
82.38, H 4.75, N 6.00; found: C 82.37, H 4.81, N 5.93.
Diketo bisisoquinoline 8 (4.00 g, 11.1 mmol) was dissolved
in 200 mL of DMF with 3.87 g (24.4 mmol) of p-fluoroben-
zoyl chloride. After 30 min of stirring, 2.42 g (24.4 mmol) of
TMSCN were added, along with a catalytic amount of AlCl3.
The flask was stoppered and stirred for 4 days. The solution
was poured into water (500 mL) and filtered: 7.62 g (89%).
The crude product was purified by column chromatography
(silica gel, 40:60 hexanes/ethyl acetate) and recrystallized
from chloroform:hexanes, mp 249.0–249.5 ꢀC. FTIR (KBr);
1677.2 cmꢁ1, 1651.1 cmꢁ1 (C¼¼O).
2-(p-Fluorobenzoyl)-4-benzoyl-l,2-dihydroisoquinaldo-
nitrile (15)
Ketone 14 (1.00 g, 4.3 mmol) was dissolved in 20 mL of
CH2Cl2, after which 0.745 g (4.7 mmol) of p-fluorobenzoyl
chloride was added. After 30 min of stirring, 0.466 g (4.7
mmol) of TMSCN was added along with a catalytic amount
of AlCl3. The reaction was stoppered and stirred for 7 days.
The solution was poured into 500 mL of water, stirred over-
night, and filtered: 1.40 g (85%). After three recrystalliza-
tions from toluene:hexanes, the pure product was obtained,
lH NMR (270 MHz, CDCl3); d 6.47, s, 2H, H1; 7.16–7.18, m,
8H, o to F and H5 and H8; 7.26, s, 4H, ArH; 7.68–7.78, m, 4H,
H6 and H7; 7.82, s, lH, H3. EI MS: 686 (Mþ). ELEM. ANAL.,
Calcd. for C42H24F2N4O4: 73.46, 3.52, 8.16; found: C 73.20, H
3.65, N 8.16.
ꢀ
mp 170.4–171.7 C.
1H NMR (270 MHz, CDCl3): d 8.49, s, lH, H3; 7.13, d (J ¼ 8),
1H, H5; 7.38–7.46, m, 5H, ArH; 7.54, d (J ¼ 8), 1H, H8; 7.64–
7.80, m, 6H, ArH. ELEM. ANAL., Calcd. for C24H15N2O2F: C
75.38, H 3.95, N 7.33; found: C 75.38, H 3.96, N 7.33.
Attempted Synthesis of p-Bis{4-[1-(p-fluorobenzoyl)
isoquinoly]carbonyl}benzene (10) from Diketo
Reissert Compound 9
To a stirring solution of 0.50 g (0.73 mmol) of the diketo
Reissert compound 9 in 20 mL of DMF at 0 ꢀC NaH (0.07 g
of 60% dispersion, 2 mmol) was added. The reaction mix-
Attempted Synthesis of 4-Benzoyl-l-(p-fluorobenzoyl)
isoquinoline (16) by Rearrangement of Bis(Reissert
Compound) 15
ꢀ
ture was stirred for 2 days at 0 C, poured onto ice, filtered,
and dried: 0.30 (68%) of dark solid. FTIR (KBr): 1670.4
To a stirring solution of 0.50 g (1.3 mmol) of the Reissert
compound 15 in 20 mL DMF at 25 ꢀC NaH (0.07 g of 60%
dispersion, 2 mmol) was added. The reaction mixture was
stoppered and stirred for 1 day, poured onto ice, filtered and
dried: 0.15 g (33%). TLC indicated that there were at least
l
cmꢁ1(broad). The H NMR (270 MHz, CDCl3) spectrum was
complicated due to side products resulting from the pres-
ence of the carbonyl group, but did indicate the presence
of some desired product 10. However, no pure compound
could be isolated by either recrystallization or column
chromatography.
l
seven components in the product mixture. The H NMR spec-
trum was complicated due to side products resulting from
the presence of the carbonyl group.
1-(p-Fluorobenzoyl)isoquinoline (12)
To a stirring solution of 1.00 g of 2-(p-fluorobenzoyl)-1,2-
dihydroisoquinaldonitrile (11)25 in 40 mL of DMF at 25 ꢀC,
NaH (0.17 g of 60% dispersion in oil, 4.3 mmol) was added.
The reaction mixture was stirred for 36 h, poured onto ice,
and extracted with CH2Cl2: 1.63 g (90%) of viscous brown
oil, which was purified by column chromatography (silica
gel, 60:40 hexanes:ethyl acetate) and recrystallized twice
from ethyl acetate:hexanes, yellow solid, mp 91.0–92.2 ꢀC.
FTIR (KBr): 1664.1 cmꢁ1 (C¼¼O).
2-(p-Fluorobenzoyl)-4-benzyl-l,2-dihydroisoquinaldo-
nitrile (17)
4-Benzylisoquinoline (13)15 (5.00 g, 22.8 mmol) was dis-
solved in 50 mL of CH2Cl2. Then, 4.45 g (68.4 mmol) of KCN
dissolved in 11 mL of water were added. The resulting mix-
ture was stirred for 15 min prior to the dropwise addition
of 7.23 g (45.6 mmol) of p-fluorobenzoyl chloride over 2 h.
The mixture was stirred for 20 h, after which 100 mL of
water were added. The layers were separated. The organic
layer was washed with water 3ꢃ, 10% HCI 3ꢃ, H2O 3ꢃ,
10% NaHCO3 3ꢃ, and water 3ꢃ. The solution was dried
1H NMR (270 MHz, CDCl3): d 7.12–7.18, m, 2H, o to F; 7.61–
8.04, m, 6H, ArH; 8.22, d (J ¼ 8), 1H, H3; 8.59, d (J ¼ 8), 1H,
SYNTHESIS OF HETEROCYCLIC MONOMERS VIA REISSERT CHEMISTRY, GIBSON ET AL.
3863

JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
over NaSO4 for 1 day and concentrated: 6.96 g (83%). The
crude product was purified by column chromatography
(silica gel, 90:10 hexanes:ethyl acetate) and recrystallized
from hexanes:ethyl acetate, mp 148.3–149.3 ꢀC. FTIR (KBr):
1664.1 cmꢁ1 (C¼¼O).
8), 2H; 8.31, d (J ¼ 8), 2H; 8.39, s, 2H, H3. ELEM. ANAL.,
calcd for C56H42F2N2O4 ꢂ 1/5 (C4H8O2): C 79.11, H 5.07, N
3.25; found: C 78.72, H 4.88, N 3.23.
a,a0-Bis[4-{1-a-hydroxy-p-fluorobenzyl)isoquinolyl}]-p-
xylene (21)
1H NMR (270 MHz, CDC13): d 3.82, AB q (J ¼ 14), 2H,
ArCH2; 6.37, s, lH, H3; 6.52, s, 1H, H1; m, 7.08–7.63, 11H,
ArH; m, 8.09–8.15, 2H, a to CO. ELEM. ANAL., Calcd. for
Bisisoquinoline Reissert compound 19, 10.00 g (15.4 mmol),
4.21 g (33.9 mmol) of p-fluorobenzaldehyde, and 1.07 g of
benzyltrimethylammonium chloride were dissolved in 113
mL of acetonitrile. After 30 min of stirring, 14 mL of 50%
NaOH were added. The reaction was allowed to stir for 6 h
with heating in an oil bath to reflux the acetonitrile. The
mixture was diluted with 1 L of water. The product was
extracted with CHCl3 and washed 3ꢃ with water, dried over
Na2SO4 and concentrated by evaporation: 8.84 g; FTIR: ester
C¼¼O at 1715.6 cmꢁ1 and no OH group, signifying incomplete
hydrolysis. The crude product was dissolved in 200 mL etha-
nol, 100 mL H2O, and 40 g (0.71 mol) of KOH were added.
After refluxing overnight, the product was isolated by precip-
C24H17N2OF: C 78.25, H 4.65, N 7.60; found: C 77.99, H 4.71,
N 7.53.
1-(p-Fluorobenzoyl)-4-benzylisoquinoline (18)
To a stirring solution of 0.63 g (1.7 mmol) of the 4-benzyli-
soquinoline Reissert compound 17 in 40 mL of DMF at 25
ꢀC, NaH (0.08 g of 60% dispersion, 2 mmol) was added. The
mixture was stirred for 2 days, poured onto ice, and filtered:
0.46 g (79%). The crude product was purified by column
chromatography (silica gel, 60:40 hexanes:ethyl acetate) and
recrystallized from ethyl ꢁa1cetate:hexanes, mp 135.0–136.3
ꢀC. FTIR (KBr): 1723.0 cm (C¼¼O).
itation into water: 6.45
g (73%); recrystallized from
CH2Cl2:hexane, colorless crystals, mp 174.2–175.5 ꢀC. FTIR
(KBr): 3378 cmꢁ1 (OH).
lH NMR (270 MHz, CDCl3): d 4.47, s, 2H, ArCH2; 7.07–7.42,
m, 7H, o to F and ArH; 7.76–7.79, m, 2H, m to F; 8.03–8.39,
m, 4H, H5–8; 8.53, s, 1H, H3. EI MS: m/z 341 (Mþ), 340 (M-
H)þ. HR ESI MS: m/z 364.1127 (M þ Na)þ, Calcd. for
1H NMR (270 MHz, CDCl3): d 4.37, s, 4H, ArCH2; 6.21, br, 2H,
OH; 6.32, br, 2H, methine; 6.96, t (J ¼ 9), 4H, o to fluorine;
7.14, s, 4H, ArH; 7.29, m, 4H, m to fluorine; 7.46, t (J ¼ 8),
2H, H6; 7.60, t (J ¼ 8), 2H, H7; 7.92, m, 4H, H5, and H8; 8.37,
s, 2H, H3. ELEM. ANAL., Calcd. for C40H30F2N2O2 ꢂ 1.5 H2O: C
75.57, H 5.23, N 4.41; found C: 75.94, H: 4.86, N: 4.52. Anal-
ogous hydrolysis of diester 20 afforded the diol 21 in 79%
yield.
C
23H16FNO þ Na: 364.1108, error 5.2 ppm; 342.1299 (M þ
H)þ, Calcd. for C23H16FNO þ H: 342.1289, error 2.9 ppm.
a,a0-Bis[1-cyano-2-(o-toluyl)-1,2-dihydroisoquinolin-4-yl]-
p-xylene (19)
Bisisoquinoline 7 (8.00 g, 22.2 mmol) was dissolved in 150
mL of DMF, after which 7.55 g (48.8 mmol) of o-toluyl chlo-
ride were added. After 30 min of stirring, 4.84 g (43.3
mmol) of TMSCN were added, along with a catalytic amount
of AlCl3. The flask was stoppered and stirred for 5 days. The
solution was poured into water and the precipitate was fil-
tered: l8.6 g (93%). After three recrystallizations from chlor-
oform:hexanes, the pure product was obtained, mp 220.5–
p-Bis[4-{1-(p-fluorobenzoyl)isoquinoly}carbonyl]
benzene (10)
A mixture of 12.76 g (16 mmol) of diol 21, 300 mL benzene,
and 100 g MnO2 was allowed to reflux for 12 h using a
Dean-Stark trap. The oxides were filtered through Celite and
washed with CH2Cl2 in a Soxhlet extractor for 5 days. The
combined extract was dried over MgSO4. The solvent was
removed: yellow solid, 6.13 g (61%). The crude product was
recrystallized 3ꢃ from ethanol, light yellow crystals, mp
228.2–230.2 ꢀC. FTIR (KBR): 1664.1 cmꢁ1, (C¼¼O); 1598.7
cmꢁ1 (C¼¼C).
ꢁ1
ꢀ
221.5 C. FTIR (KBr): 1672 cm (C¼¼O).
1H NMR (270 MHz, CDCl3): d 2.27, s, 6H, CH3; 3.60, AB q (J
¼ 14), 4H, ArCH2; 6.11, s, lH, H3; 6.76, s, lH, H1; 7.04–7.32,
m, 22H, Ar. ELEM. ANAL., Calcd. for C44H34N4O2: C 81.21, H
5.27, N 8.61; found C: 81.19, H: 5.33, N: 8.56.
lH NMR (270 MHz, CDCl3): d 7.18, t (J ¼ 9), 4H, o to F; 7.72,
t (J ¼ 8), 2H, H6; 7.84, t (J ¼ 8), 2H, H7: 8.03, m, 8H, phenyl
and m to F; 8.24, m, 4H, H5 and H8; 8.71, s, 2H, H3. ELEM.
ANAL., Calcd. for C40H22F2N2O4 ꢂ 1/4 H2O: C 75.17, H 3.55,
N 4.38; found C 75.28, H 3.49, N 4.37.
a,a0-Bis[4-{1-(o-Toluyloxy-p-fluorobenzyl)isoquinolyl}]-p-
xylene (20)
To a stirring solution of 8.00 g (12 mmol) of Reissert com-
pound 19 and 2.88 g (0.23 mmol) of p-fluorobenzaldehyde
in 150 mL of DMF, NaH ꢀ(1.06 g of 60% dispersion in oil, 26
mmol) was added at 25 C. The reaction mixture was stirred
for 2 days, poured into water, and filtered: 8.38 g (86%).
The crude product was purified by column chromatography
(silica gel, 50:50 hexanes/ethyl acetate) and recrystallized
once from ethyl acetate:hexanes, mp 145.6–146.7 ꢀC. FTIR
(KBR): 1714 cmꢁ1 (C¼¼O).
N,N0-(4,40-Oxybisbenzoyl)-bis{4,40-(p-fluorobenzyl)-1,2-
dihydroisoquinaldonitrile} (24)
A solution of 6.55 g (27.6 mmol) of 4-(p-fluorobenzyl)isoqui-
noline, (23),23 and 3.01 g (10.5 mmol) of 4,40-oxybis(benzoyl
chloride) (22, made by treatment of the diacid with SOCl2)
in (dry) CH2Cl2 was stirred under N2 for 20 min before 3.01
mL (22.6 mmol) of TMSCN were added via syringe, followed
by a cat. amount of AlCl3. Stirring was continued for 7 days,
after which the reaction was quenched with 150 mL of
water. Following 2 h of stirring, the organic phase was
1H NMR (270 MHz, CDCl3): d 2.58, s, 6H, CH3; 4.31, s, 4H,
ArCH2; 7.02, t (J ¼ 10), 4H, o to F; 7.09, s, 4H; 7.2–7.7, m,
14H; 7.77, s, 2H, methine; 7.95, d (J ¼ 8), 2H; 8.10, d (J ¼
3864
INTERSCIENCE.WILEY.COM/JOURNAL/JPOLA

ARTICLE
washed in a separatory funnel: 3ꢃ water, 3 ꢃ 10% HCI, 3 ꢃ
10% NaHCO3, 3 ꢃ 5% NaOH. After drying over Na2SO4, the
solvent was removed via rotary evaporation and the com-
pound dried under vacuum: 5.42 g (67%). Four recrystalliza-
tions from EtOH:hexanes (small amount of toluene) afforded
p-{1-[4-(p-Fluorobenzyl)isoquinolyl]carbonyl}diphenyl
Ether (29)
To a solution of 12.16 g (16.2 mmol) of bis(Reissert com-
pound) 24 in 170 mL of freshly distilled THF were added
1.42 g (59.3 mmol) of NaH (60% dispersion in mineral oil)
in one portion. The mixture was maintained at 60 ꢀC under
N2 for 2 days, diluted with CH2Cl2 and then washed with
water in a separatory funnel. The solution was dried over
MgSO4 for 24 h. Removal of solvent afforded 9.74 g (86%) of
the crude product, which was reprecipitated from chloro-
form into hexane and recrystallized twice from EtOAc/hex-
ꢀ
a light yellow powder, mp 156.3–160.5 C.
1H NMR (270 MHz, CDCl3): d 3.80, AB q (J ¼ 14), 4H, ArCH2;
6.43, s, 2H, H3; 6.53, s, 2H, H1; 6.96, t (J ¼ 9), 4H, o to F;
7.05, d, (J ¼ 7) 4H, o to O; 7.18–7.39, m, 12H, ArH; 7.63, d (J
¼ 7), 4H, o to C¼¼O. ELEM. ANAL., Calcd. for C48H32F2N4O3:
C 76.79, H 4.30, N 7.46; found: C 76.29; H 4.35; N 7.26.
ꢀ
ane, mp 115.2–117 C.
The above reaction on a larger scale using 22.30 g (94
mmol) of 23 produced 24.25 g (70%) of crude product.
1H NMR (270 MHz, CDCl3): d 4.44, s, 4H, ArCH2; 6.98 0, t (J
¼ 9), 4H, o to F; 7.07–7.21, m, 8H, o to O and ArCH2; 7.61, t
(J ¼ 8), 2H, H6; 7.72, t (J ¼ 8), 2H, H7; 7.98–8.09, m, 6H, o
to C¼¼O and H5; 8.26, d (J ¼ 8), 2H, H8; s, 8.45, 2H, H3. FTIR:
4,40-Sulfonylbis(benzoic Acid) (26)
A solution of 40.12 g (120 mmol) of dimethyl 4,40-sulfonyl-
bis(benzoate) (25) and 19.64 g (0.350 mol) of KOH in 300
mL of absolute ethanol was heated at reflux overnight. The
dipotassium salt was filtered, dissolved in water and acidi-
fied by adding conc. sulfuric acid dropwise until pH 2. The
acid was filtered, washed with water and dried: 35.16 g
(96%), mp > 400 ꢀC. FTIR: COOH, 3200–2500 cmꢁ1; C¼¼O,
C¼¼O, 1664.1 cmꢁ1
;
C¼¼C, C¼¼N, 1598.7–1507.1 cmꢁ1
;
CAOAC, 1238.9 cmꢁ1. ELEM. ANAL., Calcd. for C46H30F2N2O3
ꢂ 1/3 C4H8O2: C 78.23, H 4.52, N 3.86; found: C 78.06, H
4.45, N 4.19. FAB MS (in 3-nitrobenzyl alcohol): m/z 697.23,
(MþH)þ; 236.0, (C16H11NF)þ; Calcd. for C46H30F2N2O3, M ¼
696.2.
1690 cmꢁ1; SO2, 1284 and 1160 cmꢁ1
.
p-{1-[4-(p-Fluorobenzoyl)isoquinolyl]carbonyl}diphenyl
Ether (30)
A mixture of 9.00 g (13 mmol) of 29 and 90.0 g (1.03 mol)
of MnO2 in 300 mL of benzene was heated at reflux via oil
bath for 24 h using a Dean-Stark trap. The mixture was fil-
tered through a Celite bed, which was washed with CHCl3
and hot EtOAc. The solutions were combined, dried over
MgSO4 and evaporated: 5.03 g (57%). An analytically pure
sample was obtained after four recrystallizations from
4,40-Sulfonylbis(benzoyl Chloride) (27)
A solution of 34.16 g (111.5 mmol) of 26 and 84.0 mL (1.12
mol) of SOCl2 was allowed to reflux for 2 h, after which a 2–
3 drops of DMF were added as a catalyst and refluxing was
continued for an additional 22 h. At the end of the reaction,
the excess SOCl2 was removed via reduced pressure distilla-
tion. Recrystallization from toluene gave 35.52 g (93%) of a
ꢀ
EtOH:hexanes, mp 176.8–178.5 C.
ꢀ
white fluffy solid, mp 159–160 C. FTIR: no carboxyclic acid
1H NMR (270 MHz, CDCl3): d 7.14–7.23, m, 8H, o to F and
ArCH2; 7.69, t (J ¼ 8), 2H, H6; 7.79, t (J ¼ 8), 2H, H7; 7.94–
8.11, 8H, o to C¼¼O and o to O; 8.10, d (J ¼ 8), 2H, H5; 8.24,
band at 3200 cmꢁ1
.
N,N0-[4,40-Sulfonylbis(benzoyl}]-bis{4,40-(p-fluorobenzyl)-
1,2-dihydroisoquinaldonitrile} (28)
d (J ¼ 8), 2H, H8; 8.65, s, 2H, H3. FTIR: C¼¼O 1662 cmꢁ1
;
CAOAC, 1251 and 1151 cmꢁ1. ELEM. ANAL., Calcd. for
To a solution of 3.63 g (15.3 mmol) of 4-(p-fluorobenzyl)iso-
quinoline (23)23 and 2.51 g (7.3 mmol) of diacid chloride 27
in 75 mL of dry CH2Cl2 2.10 mL (15.8 mmol) of TMSCN
were added via syringe, followed by a cat. amount of AlCl3.
The mixture was stirred under N2 for 6 days, quenched with
300 mL of water and stirred for 2 h. The organic layer was
washed 3ꢃ water, 3 ꢃ 5% NaOH, 3 ꢃ 10% NaHCO3, 3 ꢃ
10% HCl, and 3ꢃ water and dried over Na2SO4 for 1 day.
Solvent removal and drying afforded 3.08 g (53%) of crude
solid, which after three recrystallizations from EtOAc/hexane
produced a yellow solid, mp 165.8–166.7 ꢀC. The reaction
was repeated using 18.51 g of 23, yielding 17.70 g (58%).
C
46H26F2N2O5 ꢂ 1/2 C2H5OH: C 75.49, H 3.91, N 3.75, F
5.08; found: C 75.30, H 3.74, N 3.83, F 4.57.
p-{1-[4-(p-Fluorobenzyl)isoquinolyl]carbonyl}diphenyl
Sulfone (31)
To a solution of 14.14 g (17.7 mmol) of bis(Reissert com-
pound) 28 in 200 mL of freshly distilled THF 1.56 g (39.0
mmol) of NaH (60% dispersion in light mineral oil) were
ꢀ
added. The mixture was heated at 60 C under N2 for 2 days
and diluted with CH2Cl2. The solution was washed repeat-
edly with water, dried over MgSO4 for 1 day, and evaporated:
9.69 g (76%) of dried product, which was purified on a sili-
cia gel column using 65:35 EtOAc:hexane, reprecipitated
thrice from CHCl3 into hexane and recrystallized twice from
1H NMR (270 MHz, CDCl3): d 3.82, AB q (J ¼ 14), 4H, ArCH2;
6.22, s, 2H, H1; 6.56, s, 2H, H3; 6.92, t (J ¼ 9), 4H, o to F;
7.16–7.38, m, 16H, ArH; 7.72, d (J ¼ 8), 2H, H5; 8.03, d (J ¼
8), 2H, H8. FTIR: C¼¼O, 1670 cmꢁ1; C¼¼C, C¼¼N, 1598–1507
cmꢁ1; ASO2A, 1395, 1330 cmꢁ1. ELEM. ANAL., Calcd. for
ꢀ
EtOAc:hexane, mp 153.7–155.2 C.
1H NMR (270 MHz, CDCl3): d 4.45, s, 4H, ArCH2; 6.99, t (J ¼
9), 4H, o to F; 7.17, m, 4H, Ar-H; 7.66, t (J ¼ 8), 2H, H6; 7.75,
t (J ¼ 8), 2H, H7; 8.01–8.09, m, 12H, Ar-H; 8.42, s, 2H, H3.
FAB MS (in 3-nitrobenzyl alcohol): m/z 745.196, (MþH)þ;
C48H32N4O4SF2: C 72.17, H 4.04, N 7.01; found: C 71.93, H
4.09, N 6.94.
SYNTHESIS OF HETEROCYCLIC MONOMERS VIA REISSERT CHEMISTRY, GIBSON ET AL.
3865

JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
634, (M-CH3C6H4F)þ; 526, (M-2CH2C6H4F)þ; isotopic peaks
were present in theoretical intensities. Exact mass of
crude product was recrystallized from ethanol 4ꢃ, tan crys-
tals, mp 163.1–163.6 ꢀC. FTIR (KBr): 1677 cmꢁ1 (C¼¼O).
C46H30N2O4SF2, M ¼ 744.1973.
1H NMR (270 MHz, CDC13): d 3.80, AB q (J ¼ 15 Hz), 2H,
ArCH2; 6.40, s, lH, H1; 6.60, s, 1H, H3; 6.95, t (J ¼ 8 Hz), 2H,
o to F; 7.2–7.7 m, 11H, ArH. ELEM. ANAL., Calcd. for
4,40-[Sulfonylbis(p-phenyleneoxy)]dibenzoic Acid (33)
This compound was prepared in 72% yield by the method
reported by Idage.26
C24H17N2OF: C 78.25, H 4.65, N 7.60; found: C 78.29, H 4.66.
4,40-[Sulfonylbis(p-phenyleneoxy)]dibenzoyl Chloride
(34)
a,a0-Dihydroxy-a,a0-Bis{1-[4-(p-fluorobenzyl)isoquinolyl]}-
p-xylene (37)
The crude acid 33, 12.00 g (24.5 mmol), and 18 mL (0.245
mol) of SOCl2 were heated at reflux for 2 h, after which 3–4
drops of DMF were added. The heating was continued for 2
h; the mixture was left overnight at room temperature. The
excess thionyl chloride was distilled off under reduced pres-
sure. The crude product was recrystallized from toluene, mp
179–184 ꢀC [lit. mp26 184–189 ꢀC]. FTIR: C¼¼O stretch
@1735 cmꢁ1; CAOAC asym. and sym. stretch @ꢁ11250 and
1104 cmꢁ1, respectively; CACl bending @ 885 cm and the
2-Benzoyl-4-(p-fluorobenzyl)-1,2-dihydroisoquinaldonitrile (36),
14.7 g (40 mmol), 2.95 g (22 mmol) of terephthaldehyde, and
0.20 g of tetrabutylammonium bromide were dissolved in 250
mL of acetonitrile. After 30 min of stirring, 20 mL of 50% NaOH
were added. The mixture was heated at reflux for 1.5 h, diluted
with 800 mL of H2O and extracted with CH2Cl2 (5 ꢃ 50 mL). The
extract was washed 5ꢃ with water, dried over Na2SO4 and con-
centrated by evaporation: 12.94 g; FTIR: ester C¼¼O at 1715.6
cmꢁ1 and no OH group, signifying incomplete hydrolysis. The
crude product was dissolved in 265 mL ethanol, 150 mL H2O,
and 52 g of KOH were added. After refluxing 4 h, the mixture
was concentrated and precipitated into 750 mL of water: 8.50 g
(70%); recrystallized 4ꢃ from ethanol, colorless crystals, mp
225.0–225.3. FTIR (KBr): 3545–3600 cmꢁ1 (OH).
loss of the carboxylic acid bands @ 3200–2561 cmꢁ1
.
1H–NMR (270 MHz, CDCl3): d 7.10, d (J ¼ 8), 2H; 7.20, d (J
¼ 8), 2H; 8.05, d (J ¼ 8), 2H; 8.15, d (J ¼ 8), 2H.
N,N0-[Sulfonylbis(p-phenyleneoxy)]-bis{4,40-(p-fluoroben-
zyl)-1,2-dihydroisoquinaldo-nitrile) (35)
1H NMR (270 MHz, CDCl3): d 4.36, s, 4H, ArCH2; 6.15, d (J ¼
6), 2H, OH; 6.29, d (J ¼ 6), 2H, methine; 6.97, t (J ¼ 9), 4H,
o to fluorine; 7.15, t (J ¼ 6), 4H, m to fluorine; 7.26, s, 4H,
ArH; 7.43, t (J ¼ 8), 2H, H6; 7.58, t (J ¼ 8), 2H, H7; 8.06, m,
4H, H5 and H8; 8.35, s, 2H, H3. ELEM. ANAL., Calcd. for
To 3.87 g (16.3 mmol) of 4-(p-fluorobenzyl)isoquinoline
(23)23 and 4.00 g (7.6 mmol) of 4,40-[sulfonylbis(p-phenyl-
eneoxy)]dibenzoyl chloride (34) in 75 mL of dry (molecular
sieves) CH2Cl2 under N2 2.23 mL (16.7 mmol) of TMSCN
were added via syringe along with a cat. amount of AlCl3. Af-
ter 4 days, the mixture was quenched into water. The or-
ganic layer was washed 3ꢃ H2O, 2 ꢃ 5% NaOH, 1 ꢃ 10%
NaHCO3, 3 ꢃ 10% HCI, and 3 ꢃ H20, and finally dried over
Na2SO4. Removal of solvent afforded 4.48 g (60%) of a yel-
low solid, which was dissolved in CHCl3 and precipitated
into to hexane three times, subjected to column chromatog-
raphy (65:35 EtOAc:hexane) and two recrystallizations from
C
40H30F2N2O2 ꢂ H2O: C 76.66, H 5.15, N 4.47; found C:
76.48, H: 4.90, N: 4.40.
p-Bis{1-[4-(p-fluorobenzoyl)isoquinoly]carbonyl}benzene
(38)
A mixture of 5.78 g (9.5 mmol) of diol 37, 180 mL benzene
and 60 g MnO2 was allowed to reflux for 12 h using a Dean-
Stark trap. The oxides were filtered through silica gel, and the
latter was washed with CH2Cl2 and then methanol. The solvent
was removed: yellow product, 2.72 g (45%). (The low yield
reflects the fact that the MnO2 was not Soxhlet extracted in
this case.) The crude material was recrystallized from ethanol
2x, light yellow fluffy crystals, mp 237.5–238.5 ꢀC. FTIR
(KBR): 1667, 1678 cmꢁ1, (C¼¼O); 1597 cmꢁ1 (C¼¼C).
ꢀ
EtOAc:hexane, mp 154–156 C.
1H NMR (270 MHz, CDCl3): d 3.83, AB q (J ¼ 14), 4H, ArCH2;
6.37, s 2H, H1; 6.52, s, 2H, H3; 6.94, t (J ¼ 8), 4H, o to F;
7.03–7.37, m, 26H, ArH 7.60, d, 2H, H5; d (J ¼ 8), 7.95, 2H,
H8. ELEM. ANAL., Calcd. for C60H40F2N4O6 ꢂ C4H8O2: C 71.76,
H 4.52, N 5.23; found: C 71.62, H 4.12, N 5.21. FAB MS (in 3-
nitrobenzyl alcohol): m/z 983.26 (MþH)þ; 982.26Mþ; 956
(M-CN)þ; 719 (M-C17H12FN2)þ; 665 (M-CN-C17H12FN2)þ;
lH NMR (270 MHz, CDCl3): d 7.20, q (J ¼ 9), 4H, o to F;
7.70–7.84, m, 4H, H6, H7; 7.97, m, 4H, m to F; 8.10, m, 6H,
H5 and xylyl; 8.33, d (J ¼ 8), 2H, H8; 8.67, s. 2H, H3. ELEM.
ANAL., Calcd. for C40H22F2N2O4 ꢂ 1/4 H2O: C 75.17, H 3.55,
N 4.38; found C 75.05, H 3.43, 4.35.
C60H40F2N4O6S exact mass 982.2637.
2-Benzoyl-4-(p-fluorobenzyl)-l,2-
dihydroisoquinaldonitrile (36)
4-(p-Fluorobenzyl)isoquinoline (23)23 (42.71 g, 180 mmol)
was dissolved in 300 mL of CH2Cl2. Then, 35.16 g (540 mmol)
of KCN dissolved in 100 mL of water were added. The result-
ing mixture was stirred for 15 min prior to the dropwise addi-
tion of 50.60 g (360 mmol) of benzoyl chloride over 2 h. The
mixture was stirred for 20 h, after which 200 mL of water and
300 mL of CH2Cl2 were added. The layers were separated. The
organic layer was washed with water 3ꢃ, 10% HCI 3ꢃ, H2O
3ꢃ, 10% NaHCO3 3ꢃ, and water 3ꢃ. The solution was dried
over NaSO4 for 1 day and concentrated: 73 g (100%). The
Polymerization of p-Bis{4-[1-(p-fluorobenzoyl)
isoquinoly]carbonyl}benzene (10) with Bis(phenol-A) to
form Poly(heteroarylene ether) 39
Tetraketone 10 (1.0000 g, 1.57 mmol) and 0.3584 g (1.57
mmol) of bisphenol-A were dissolved in 9 mL of NMP freshly
distilled from CaH2. Then, 0.2604 g (1.57 mmol) of anhy-
drous K2CO3 and 4 mL of toluene were added. The mixtuꢀre
was heated in an oil bath under N2 and kept at 140–145 C
ꢀ
for 4 h. The temperature was then raised to 160–170 C and
3866
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ARTICLE
9 Boekelheide, V.; Weinstock, J. J Am Chem Soc 1952, 74,
maintained for 13 h. The reaction mixture was cooled,
diluted with CHCl3, filtered, acidified with acetic acid, and
precipitated into methanol to yield 0.95 g of crude tan poly-
mer: [g] ¼ 0.16 dL/g (CHCl3, 25 ꢀC); GPC (THF): Mn ¼ 4.9
660–663.
10 Gibson, H. W. J Heterocyclic Chem 1970, 7, 1169–1172.
11 (a) Anton, A.; Baird, B. R. Kirk-Othmer Encycl Chem Tech
2006, 19, 739–772; (b) Palmer, R. J. Kirk-Othmer Encycl Chem
Tech 2006, 19, 772–797; (c) Mathews, A. S.; Ha, C.-S. Curr
Trends Polym Sci 2006, 10, 69–76; (d) Bryant, R. G. Kirk-Othmer
Encycl Chem Tech 2006, 20, 264–296.
ꢀ
kDa, Mw ¼ 7.8 kDa; TGA, 5% wt. loss @ 454 C in air; DSC:
Tg ¼ 180 ꢀC and no Tm. FTIR (KBr): 1664.1 cmꢁ1 (C¼¼O),
1592.2 cmꢁ1, 1500.6 cmꢁ1 (C¼¼C), 1245.4 cmꢁ1 (CAOAC).
1H NMR (270 MHz, CDCl3): d 1.70, s, 6H, CH3; 6.90–7.09, m,
8H, o to O; 7.2–7.28, m, 4H, o to C¼¼O; 7.68, t (J ¼ 8), 2H,
H6; 7.80, t (J ¼ 8), 2H, H7; 7.92, d (J ¼ 8), 2H, H5; 8.04, s,
4H, o to C(CH3)2; 8.15, d (J ¼ 8), 2H, H8; 8.70, s, 2H, H3.
12 (a) Hoover, M. F. J Macromol Sci Chem 1970, 4, 1327–417;
(b) Vorchheimer, N. Encycl Polym Sci Eng 1987, 11, 489–507;
(c) Guo, X.; Chang, R.-K.; Hussain, M. A. J Pharm Sci 2009, 98,
3886–3902; (d) Williams, S. R.; Long, T. E. Prog Polym Sci 2009,
34, 762–782.
The authors are grateful to the donors of the Petroleum
Research Fund, administered by the American Chemical Soci-
ety, for support of this research through grant 19625 AC7. Prof.
C. F. K. Hermann was supported by a PRF Summer Fellowship.
They extend their gratitude to Prof. Thomas C. Ward and his
students for GPC, DSC, and TGA determinations. They thank the
National Science Foundation for funds to purchase the Agilent
6220 Accurate Mass TOF LC/MS Spectrometer (CHE-
0722638).
13 (a) de Abajo, J.; de la Campa, J. G. Adv Polym Sci 1999,
140, 23–59; (b) Critchley, J. P.; Wright, W. W. Heat-Resistant
Polymers; Plenum Press: New York, 1983; (c) Hergenrother,
P. M. Encycl Polym Sci Eng 1988, 7, 639–665.
14 Staniland, P. A. In Comprehensive Polymer Science; Allen,
G.; Berington, J. C., Eds.; Pergamon Press: New York, 1989;
Vol. 5, pp 484–497.
15 Minter, D. E.; Re, M. A. J Org Chem 1988, 53, 2653–2655.
16 Guilani, B.; Rasco, M. L.; Hermann, C. F. K.; Gibson, H. W.
J Heterocyclic Chem 1990, 27, 1007–1009.
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SYNTHESIS OF HETEROCYCLIC MONOMERS VIA REISSERT CHEMISTRY, GIBSON ET AL.
3867