Procedure for the rapid synthesis of the monomer 1,4-bis(chloromethyl)-2- (2-ethylhexyloxy)-5-methoxybenzene

Article abstract of DOI:10.1080/00397910802238775

The alkylation of 4-methoxyphenol with 2-ethylhexyl bromide was accelerated by using potassium tert-butoxide in dimethylformamide. Subsequent chloromethylation occurred quickly using acetic acid as a cosolvent to give the poly[(2-(2-ethylhexyloxy)-5-metho

Full text of DOI:10.1080/00397910802238775

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Procedure for the Rapid
Synthesis of the Monomer
1,4-Bis(chloromethyl)-2-
(2-ethylhexyloxy)-5-
methoxybenzene
Nichole Anderson a , Whitney Bagge a , Cindy
Webber a , Peter Zarras a & Matthew C. Davis a
a Chemistry and Materials Division , Michelson
Laboratory, Naval Air Warfare Center , China Lake ,
California , USA
Published online: 20 Oct 2008.
To cite this article: Nichole Anderson , Whitney Bagge , Cindy Webber , Peter Zarras
& Matthew C. Davis (2008) Procedure for the Rapid Synthesis of the Monomer 1,4-
Bis(chloromethyl)-2-(2-ethylhexyloxy)-5-methoxybenzene, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry,
38:22, 3903-3908, DOI: 10.1080/00397910802238775
To link to this article: http://dx.doi.org/10.1080/00397910802238775
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Synthetic Communications1, 38: 3903–3908, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802238775
Procedure for the Rapid Synthesis of the
Monomer 1,4-Bis(chloromethyl)-2-
(2-ethylhexyloxy)-5-methoxybenzene
Nichole Anderson, Whitney Bagge, Cindy Webber, Peter Zarras,
and Matthew C. Davis
Chemistry and Materials Division, Michelson Laboratory, Naval Air
Warfare Center, China Lake, California, USA
Abstract: The alkylation of 4-methoxyphenol with 2-ethylhexyl bromide was
accelerated by using potassium tert-butoxide in dimethylformamide. Subsequent
chloromethylation occurred quickly using acetic acid as a cosolvent to give
the poly[(2-(2-ethylhexyloxy)-5-methoxy-p-phenylene)vinylene] (MEH-PPV)
monomer in 61% overall yield on a 2-mol scale.
Keywords: Chloromethylation, conducting polymer, 2-ethylhexyl bromide,
MEH-PPV, poly(p-phenylvinylene), potassium tert-butoxide
Conducting polymers are a new class of semiconducting materials useful
for creating optoelectronic devices such as light-emitting diodes[1,2] and
photovoltaic cells.[3,4] Several projects required a steady supply of the
conducting polymer poly[(2-(2-ethylhexyloxy)-5-methoxy-p-phenylene)-
vinylene] (MEH-PPV)[5,6] (Fig. 1), and commercial sources were not
consistent in regards to price, quality, and molecular weight distribution.
Studies regarding our preparation of MEH-PPV will be described
elsewhere. The preparation of the MEH-PPV monomer, 2, has been
reported.[5–9] Here we show a method to prepare 2 quickly and with
excellent purity, (Scheme 1).
Received April 8, 2008.
Address correspondence to Matthew C. Davis, Chemistry and Materials
Division, Michelson Laboratory, Naval Air Warfare Center, China Lake,
CA 93555, USA. E-mail: matthew.davis@navy.mil
3903

3904
N. Anderson et al.
Figure 1. MEH-PPV.
The typical conditions for the alkylation of 4-methoxyphenol with
2-ethylhexyl bromide are refluxing in ethanol with potassium hydroxide
as base.[9,10] Using these conditions, the reaction took days to complete.
A much faster alkylation took place by using a polar, aprotic solvent and
a strong, nonnucleophilic base such as N,N-dimethylformamide and
potassium tert-butoxide. To make the reaction go to completion, a
1.75-fold excess of potassium tert-butoxide and 2-ethylhexyl bromide
were added. In this way, the reaction went to completion in 3 h at a
2-mol scale. It is believed that a portion of the 2-ethylhexyl bromide
reacts with the base, undergoing dehydrohalogenation and producing
an unknown amount of 2-ethylhexene by-product. The product 1 is
recovered in 97% yield from the aqueous workup and made analytically
pure by reduced pressure distillation.
Typical conditions for chloromethylation include saturation of the
reaction mixture with gaseous hydrogen chloride and=or multiple addi-
tions of excess paraformaldehyde and aqueous hydrochloric acid.[11]
A
serious hazard of chloromethylation under these conditions is the forma-
tion of toxic bis(chloromethyl)ether (BCME).[12,13] It was found that
running the chloromethylation of 1 in a mixture of concentrated hydro-
chloric acid and acetic acid with only 4 equivalents of paraformaldehyde
Scheme 1. Reagents and conditions; (a) KOtBu, DMF, 60 ꢀC; and (b) (CH2O),
conc. HCl, HOAc, 80 ꢀC.

MEH-PPV
3905
gave the bis-chloromethylated product 2 in just 6 h at 80 ꢀC. Although we
did not analyze the reaction for BCME, it is most likely present. How-
ever, because large excesses of hydrochloric acid and paraform-
aldehyde were not used, the amount of BCME generated is minimized.
The chloromethylation reaction is accelerated because of the acetic acid
cosolvent.[14] The reaction is a two-phase system with the upper phase
consisting of the reactant=product and acetic acid. Reaction progress is
easily monitored by proton nuclear magnetic resonance, taking an
aliquot of the upper phase. The crude product precipitates upon cooling
the reaction to room temperature but was difficult to filter in this state, so
an extractive workup was necessary. Two recrystallizations from ethanol
gave 2 in an analytically pure form in 63% yield. One report[9] gave a
melting point for 2 of 67–68 ꢀC but after multiple recrystallizations of 2
from several solvents (methanol, ethanol, 2-propanol, and 1-butanol)
and vacuum drying, a melting point greater than 50 ꢀC was never
observed.
EXPERIMENTAL
The melting point was collected on an electrothermal capillary melting-
point apparatus and is not corrected. All NMR data were collected on
a Bruker Avance II 300-MHz spectrometer (1H at 300 MHz, 13C at
75 MHz). NMR data free induction decays (FIDs) were processed using
1
NUTS software from Acorn NMR (Livermore, CA). All H and 31C
spectra are referenced to tetramethylsilane (TMS). The N,N-dimethylfor-
mamide, 99% (DMF), was purchased from Acros Organics and used as
received. All other reagents were purchased from Sigma-Aldrich
(Milwaukee) and used as received. Elemental analyses were made by
Atlantic Microlab, Inc. (Norcross, GA).
Racemic 1-(2-Ethylhexyloxy)-4-methoxybenzene (1)
A 3-L, three-necked, round-bottomed flask equipped with mechanical
stirrer and thermometer was charged with 248 g of 4-methoxyphenol
(2 mol) and 1 L of DMF. The mixture was stirred until all the solids dis-
solved. In one portion, 224 g of KOtBu (2 mol, 1 equiv) was added. After
30 min, all the solids had dissolved, the mixture was a greenish colored
solution, and the internal temperature was 50 ꢀC. An addition funnel
was equipped and charged with 386 g of 2-ethylhexyl bromide (2 mol,
1 equiv), which was run into the reaction over 45 min. Solids began to
precipitate shortly after the start of the addition, and the temperature

3906
N. Anderson et al.
peaked at 60 ꢀC. After 1 h, the temperature had cooled to 50 ꢀC, and 112 g
of KOtBu (1 mol, 0.5 equiv) was added to the reaction. The temperature
again rose to 60 ꢀC. The addition funnel was again charged with 193 g of
2-ethylhexyl bromide (1 mol, 0.5 equiv), which was run into the reaction
over 30 min. The internal temperature reached 65 ꢀC during the addition.
After 1 h, a final addition was made of 56 g of KOtBu (0.5 mol,
0.25 equiv) followed by 96.5 g of 2-ethylhexyl bromide (0.5 mol,
0.25 equiv) in a similar fashion. After stirring for 3 h, the internal tem-
perature was near rt, and thin-layer chromatography (TLC) showed all
the phenol was consumed. Water (1 L) was added to the mixture, and
all the solids were allowed to dissolve. The mixture was extracted three
times with 1-L portions of Et2O. The organic extracts were collected
and washed once with 500 mL of H2O followed by 500 mL of brine.
The organic phase was dried over 20 g of anhydrous MgSO4, filtered,
and rotary evaporated, leaving a slightly brown liquid. The crude product
was distilled at 0.1 torr, discarding all volatiles <90 ꢀC, which contained
residual 2-ethylhexyl bromide, to give the title compound (bp 115 ꢀC,
0.1 torr) as a colorless liquid (461.5 g, 97%). dH (CDCl3): 6.79 (s, 4H),
3.74 (d, J ¼ 5.7 Hz, 2H), 3.72 (s, 3H), 1.65 (m, 1H), 1.53–1.2 (m 8H),
0.92–0.82 (m, 6H); dC (CDCl3): 153.86, 115.67, 114.83, 71.47, 55.96,
39.71, 30.77, 29.33, 24.10, 23.29, 14.29, 11.32. Elemental analysis calcu-
lated for C15H24O2: C, 76.23; H, 10.24. Found: C, 76.21; H, 10.42.
Racemic 1,4-Bis(chloromethyl)-2-(2-ethylhexyloxy)-5-
methoxybenzene (2)
Warning! The following reaction must be conducted in a well-ventilated
fume hood. Mixtures of formaldehyde and hydrochloric acid are known
to generate the human carcinogen bis(chloromethyl)ether.[12]
A 3-L, round-bottomed flask equipped with mechanical stirrer was
charged with 461.5 g of 1 (1.96 mol), 891 mL of glacial HOAc, and
235.2 g of paraformaldehyde (7.84 mol, 4 equiv). The mixture was stirred
while 1.1 L conc. HCl was added. An endotherm of 3 ꢀC was observed. A
heating mantle was equipped, and the mixture was heated and stirred at
80 ꢀC. Shortly after heating, all the solids dissolved. After 6 h, virtually all
1
the starting material had been consumed by H NMR, and the heating
mantle was removed. During cooling to rt, copious white solids precipi-
tated. The mixture was extracted three times with 1.25-L portions of hex-
anes. The combined extracts were washed twice with 1-L portions of H2O
follow by two washings with 500-mL portions of brine. The organic
phase was dried over 20 g of anhydrous MgSO4, filtered, and rotary eva-
porated, leaving 630 g of a pale yellow liquid that would slowly solidify at

MEH-PPV
3907
rt into a waxy, white solid. The crude product was kept warm and liquid
and transferred to a 5-L round-bottomed flask equipped with mechanical
stirrer containing 2 L EtOH. The mixture was stirred and heated until
complete dissolution and then allowed to stir until the mixture reached
rt. The white precipitate was filtered on a coarse porosity (145- to
175-mm) glass frit. Recrystallization again from 2 L of EtOH and drying
(30 ꢀC, 10 torr) overnight gave 403 g (1.2 mol, 63%) of the title compound
as a soft, snow-white powder. Mp 45–48 ꢀC. dH (CDCl3): 6.87 (s, 1H),
6.86 (s, 1H), 4.51 (s, 2H), 4.50 (s, 2H), 3.82 (d, J ¼ 5.4 Hz, 2H), 3.79 (s,
3H), 1.69 (m, 1H), 1.56–1.33 (m, 4H), 1.32–1.21 (m, 4H), 0.89 (t,
J ¼ 7.2 Hz, 3H), 0.86 (t, J ¼ 9.7 Hz, 3H); dC (CDCl3): 151.21, 151.14,
127.29, 127.10, 114.31, 113.65, 56.56, 41.55, 41.54, 39.86, 30.87, 29.35,
24.27, 23.27, 14.29, 11.45. Elemental analysis calculated for C17H26Cl2O2:
C, 61.26; H, 7.86. Found: C, 61.39; H, 7.86.
ACKNOWLEDGMENTS
The financial support of the Environmental Security Technology Certifi-
cation Program Project Number WP-0527 managed by Dr. Bruce D.
Sartwell is gratefully acknowledged. Thanks to Drs. Jennifer A. Irvin
and David J. Irvin (China Lake) for kindly supplying 2-ethylhexyl bromide.
REFERENCES
1. Burroughes, J. H.; Bradley, D. D. C.; Brown, A. R.; Marks, R. N.; Mackay, K.;
Friend, R. H.; Burns, P. L.; Holmes, A. B. Light-emitting diodes based on
conjugated polymers. Nature 1990, 347, 539–541.
2. Braun, D.; Heeger, A. J. Visible light emission from semiconducting polymer
diodes. Appl. Phys. Lett. 1991, 58, 1982–1984.
3. Halls, J. J. M.; Walsh, C. A.; Greenham, N. C.; Marseglia, E. A.; Friend,
R. H.; Moratti, S. C.; Holmes, A. B. Efficient photodiodes from interpene-
trating polymer networks. Nature 1995, 376, 498–501.
4. Yu, G.; Gao, J.; Hummelen, J. C.; Wudl, F.; Heeger, A. J. Polymer photo-
voltaic cells: Enhanced efficiencies via a network of internal donor–acceptor
heterojunctions. Science 1995, 270, 1789–1791.
5. Wudl, F.; Srdanov, G. Conducting polymer formed of poly[2-methoxy-5-
(2-ethylhexyloxy)-p-phenylene vinylene. U.S. Patent 5,189,136, February 23,
1993.
6. Heeger, A. J.; Braun, D. Visible-light-emitting diodes fabricated from soluble
semiconducting polymers and their fabrication. U.S. Patent 5,408,109, April
18, 1995.
7. Lin, K.-F.; Fan, Y.-L.; Chow, H.-L. Origin of the methylene bonds in poly[2-
methoxy-5-(20-ethyl-hexyloxy)-1,4-phenylenevinylene] prepared according to
Gilch’s method: Novel applications. Polym. Int. 2006, 55, 938–944.

3908
N. Anderson et al.
8. Burn, P. L.; Kraft, A.; Baigent, D. R.; Bradley, D. D. C.; Brown, A. R.;
Friend, R. H.; Gymer, R. W.; Holmes, A. B.; Jackson, R. W. Chemical
tuning of the electronic properties of poly(p-phenylenevinylene)-based
copolymers. J. Am. Chem. Soc. 1993, 115, 10117–10124.
9. Ahn, T.; Jang, M. S.; Shim, H.-K.; Hwang, D.-H.; Zyung, T. Blue electro-
luminescent polymers: Control of conjugation length by kink linkages and
substituents in the poly(p-phenylenevinylene)-related copolymers. Macromo-
lecules 1999, 32, 3279–3285.
10. Amrutha, S. R.; Jayakannan, M. Control of p-stacking for highly emissive
poly(p-phenylenevinylene)s: Synthesis and photoluminescence of new tricyclo-
decane substituted bulky poly(p-phenylenevinylene)s and its copolymers. J.
Phys. Chem. B 2006, 110, 4083–4091.
11. Wood, J. H.; Gibson, R. E. Di-(a- and b-substituted aminoethyl)-benzenes, I:
2,5-Bis-(2-aminoethyl)-hydroquinones. J. Am. Chem. Soc. 1949, 71, 393–395.
12. Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether CAS
nos. 542-88-1 and 107-30-2 (substance 39). In Report on Carcinogens, 11th
ed.; U.S. Department of Health and Human Services, Public Health Service,
National Toxicology Program, Washington, DC, 2005.
13. St. Clair, J. D.; Valentine, J. R. Observation of bromomethyl ethers during
the bromomethylation of aromatic compounds. Org. Proc. Res. Dev. 2005,
9, 1013–1014.
14. Szmant, H. H.; Dudek, J. Relative chloromethylation rates of some aromatic
compounds. J. Am. Chem. Soc. 1949, 71, 3763–3765.