Accepted Manuscript

Phthalate plasticizers covalently linked to PVC via copper-free or copper catalyzed

azide-alkyne cycloadditions

Aruna Earla, Longbo Li, Philip Costanzo, Rebecca Braslau

PII: S0032-3861(16)31096-5
DOI: 10.1016/j.polymer.2016.12.014
Reference: JPOL 19250

To appear in: Polymer

Received Date: 8 September 2016

Revised Date: 1 December 2016
Accepted Date: 3 December 2016

Please cite this article as: Earla A, Li L, Costanzo P, Braslau R, Phthalate plasticizers covalently linked
to PVC via copper-free or copper catalyzed azide-alkyne cycloadditions, Polymer (2017), doi: 10.1016/
j.polymer.2016.12.014.

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.
 ACCEPTED MANUSCRIPT

for Table of Contents use only:

CO2R
O
Cl Cl
Y CO2R N N
N
N3 Y = CH2 or C=O
PVC PVC N 3

PT
R = 2-Et-Hexyl
copper or thermal Y O
Huisgen cyclization CO2R

RI
CO2R

Covalently Bonded Phthalate Plasticizers

U SC
AN
M
D
TE
C EP
AC
 ACCEPTED MANUSCRIPT

Phthalate Plasticizers Covalently Linked to PVC via Copper-Free or

Copper Catalyzed Azide-Alkyne Cycloadditions
Aruna Earla,a Longbo Li,a Philip Costanzo,b and Rebecca Braslau*,a

PT
a
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA
b
Department of Chemistry and Biochemistry, California Polytechnic State University, San Luis Obispo, CA 93407, USA

RI
ABSTRACT: Plasticization of PVC was carried out by covalently linking phthalate derivatives via copper-free (thermal)
or copper catalyzed azide-alkyne cycloadditions. Di(2-ethylhexyl) phthalate derivatives (DEHP-ether and DEHP-ester)

SC
were synthesized and appended to PVC at two different densities. The glass transition temperatures of the modified
PVC decreased with increasing content of plasticizer. PVC-DEHP-ether gave lower glass transition temperatures than
PVC-DEHP-ester, reflecting the enhanced flexibility of the ether versus ester linker.
Keywords: Internal Plasticizer; Phthalate Diester; Huisgen azide-alkyne cycloaddition

U
AN
1. Introduction

Polyvinyl chloride (PVC) is one of the most widely linked to PVC, they can migrate within the material
used and economically important thermoplastics. and leach out when the plastic comes into contact with
M

Global annual consumption in 2012 for PVC was 37.4 air [9], liquid [10-17]or some absorbent solid materials
million tons, and is expected to continue to grow [1]. [18-20]. Some polymeric plasticizers such as poly(ε-
Pure PVC is a rigid, brittle solid requiring a large caprolactone), poly(butylene adipate), and
amount of plasticizer to obtain flexibility and molda- poly(epichlorohydrin) are also utilized. The most ef-
D

bility. The most common plasticizer class currently in fective approach to avoid migration of plasticizer from
use are phthalate esters, accounting for 70% of the the PVC matrix is to covalently attach the plasticizer to
TE

global plasticizer demand in 2014 [2], with the (2- the polymer. Historically, the first example of internal
ethylhexyl) phthalate diester DEHP 1 (Fig. 1) being the plasticization of PVC was the work of Michel et al [21]
most popular. However, the adverse developmental using nucleophilic substitution of the chlorine atoms
[3,4], reproductive [5,6], neurological [7] and immune with 2-ethylhexyl esters of o-mercaptobenzoic acid 2
EP

[8] health effects of many phthalates has led to a search and thioglycolic acid 3 (Fig. 2). The glass transition
for alternative plasticizers. temperatures decreased as the degree of substitution
increased. The plasticizing power of the thioglycolic
ester is greater than that of the ethylhexyl ester of o-
C

mercaptobenzoic acid. Likewise, Reinecke et al [22].

demonstrated the internal plasticization of PVC, initial-
ly via thiolate nucleophilic substitution of some of the
AC

chlorine atoms with two phthalate-based thiol deriva-

tives: di(2-ethylhexyl) 5-mercaptophthalate (DEHP-
SH) 4 and di(2-ethylhexyl) 5-mercaptoisophthalate
Fig. 1. Structure of the Most Common Phthalate (isoDEHP-SH). The degree of functionalization ob-
Plasticizer: DEHP tained was 23 mol% for DEHP-SH and 30 mol% for
Other common small molecule plasticizers include isoDEHP-SH. This group has expanded this chemistry
terphthalates, 1,2-cyclohexane-dicarboxylic acid to include a variety of aromatic and heteroaromatic
diisononyl ester (Hexamoll® DINCH®), epoxidized sulfides [23,24] bearing esters, amides, ureas, ure-
vegetable oils, citrates, mellitates, adipates, benzoates, thanes, sulfonate esters and sulfornamides, often bear-
maleates, succinates, sebacates, phosphates, isosorbide ing 2-ethylhexyl groups or Jeffamines to give impres-
esters. Because these plasticizers are not covalently sive low Tg values at 20% or 40% weight sulfide.

1
 ACCEPTED MANUSCRIPT

PT
RI
U SC
Fig. 2. Internal Plasticizers Prepared by Sulfur Nucleophile Displacement of Chloride on PVC
Aromatic sulfides such as PVC-DEHP-SH 4 and sub- Cycloadditions of azides and alkynes in a (3+2) fash-
AN
stituted triazine sulfides 5 show good plasticization, ion to form triazoles [25,26] have become widely pop-
zero migration and no elimination, a high loading (typ- ular due to both the chemoselectivity and mild reaction
ically 40%) of the plasticizer is required to lower the Tg conditions. Inspired by the structural similarity be-
to desirable temperatures. The longterm stability of tween phthalate esters and 4,5-diester 1,2,3-triazoles,
M

these aryl and heteroaryl sulfide derivatives is a we recently demonstrated the covalent attachment of
concern; oxidation products are expected as the the phthalate mimics using thermal Huisgen cycloaddi-
material ages in air; elimination becomes a possibility. tion of PVC-azide with electron-poor di(2-ethylhexyl)
acetylenedicarboxylate [27].
D
TE
C EP
AC

Fig. 3. Internal Plasticizers by Azide Displacement of Chloride on PVC followed by Triazole Formation

2
 ACCEPTED MANUSCRIPT

Experimental values for the glass transition tempera- is miscible with PVC, but imparts little plasticization.
tures (Tg) of pure PVC, 15% displacement of chlorine Yang et al [29] carried out covalent modification of
by azide (15% PVC-Azide), and 15% plasticized PVC PVC by CuAAC of PVC-azide with an alkyne tethered
bearing 2-ethylhexyl triazole diester (15% PVC- to naturally abundant cardanol. The modified polymer
DEHT) 6 were 83 °C, 76 °C, and 65 °C, respectively, PVC-cardanol 8 exhibited a decreased Tg = 51 °C,
indicating plasticization by the phthalate mimic (Fig. thermal stability and no migration. Herein are reported
3). However, the Tg of 15% PVC-DEHT is way too phthalate (2-ethylhexyl) diesters covalently linked to
high for most commercial applications. This only mod- PVC by two different rotationally flexible tethers.
erate reduction in Tg may be due to the restricted rota- These internal plasticizers are attached either by using

PT
tion of the plasticizer mimic attached directly to the mild, copper-free thermal Huisgen cycloaddition, or by
PVC polymer chain. A flexible linker between the tria- copper-catalyzed azide-alkyne cycloadditions. Specif-
zole ring and the plasticizer would provide additional ically, phthalate diesters bearing a terminal alkyne
degrees of rotation. Following our triazole phthalate were designed with either an ester or ether linkage,

RI
plasticizer mimic publication, similar triazole cycload- with triazole formation as the chemoselective attach-
ditions to form internally plasticized PVC have been ment strategy, to form PVC-DEHP-ether 9 and PVC-
published. Recently, Tasdelen et al [28] synthesized DEHP-ester 10 (Fig. 4). The synthesis of phthalate-

SC
graft copolymers by photoinduced copper-mediated based terminal alkynes DEHP-ether and DEHP-ester
azide-alkyne cycloaddition (CuAAC) of alkyne termi- and their covalent attachment to PVC, and the resulting
nated poly(ε-caprolactone) (PCL) and PVC-azide. The plasticization as reflected by the Tg values of the result-
single Tg = 76 °C for PVC-g-PCL 7 indicates that PCL ing materials is described.

U
AN
M
D
TE
EP

Fig. 4. Internally Plasticized PVC-DEHP Derivatives 9 and 10 with Flexible Tethers

2. Results and discussion Benzylic bromination using N-bromosuccinimide

C

(NBS) and catalytic benzoyl peroxide in refluxing ben-

For the preparation of DEHP-ether, three synthetic zene for 1h afforded dimethyl-4-bromomethylphthalate
routes were explored. The first approach (Scheme 1) 12 in 77% yield. Williamson ether synthesis of benzyl
AC

involved Diels-Alder reaction of isoprene and dime- bromide 12 with propargyl alcohol in the presence of
thylacetylene dicarboxylate catalyzed by anhydrous sodium hydride gave the respective ether 13 in 49%
silica gel [30] to give cyclohexadiene dicarboxylate 11 yield. Transesterification with deprotonated 2-
in 96% yield. Oxidation using Dess-Martin perio- ethylhexanol afforded the key terminal alkyne DEHP
dinane gave dimethyl-4-methylphthalate in 68% yield. ether 14 in 32%.

3
 ACCEPTED MANUSCRIPT

PT
RI
Scheme 1. First Diels-Alder Route to DEHP-ether 14

U SC
AN
M
D

Scheme 2. Second, More Convergent Diels-Alder Route to DEHP-ether 14

TE
C EP
AC

Scheme 3. 4-Methylphthalic Anhydride Route to DEHP-ether 14

In the second, more convergent approach (Scheme 2), ence of activated anhydrous silica gel [30] to give di(2-
Diels-Alder reaction of di(2-ethylhexyl) acetylene di- ethylhexyl) 4-methylphthalate 15 in 97% yield. Ben-
carboxylate and isoprene was carried out in the pres-
4
 ACCEPTED MANUSCRIPT
zylic bromination using NBS and catalytic benzoyl
peroxide gave di(2-ethylhexyl) 4-(bromomethyl)-
phthalate 16 in 32% yield. The SN2 reaction with sodi-
um propargylate afforded ether 14 in 76% yield. The
third and the most efficient method to synthesize pro-
pargyl ether 14 started with commercially available 4-
methylphthalic anhydride (Scheme 3). Switching to
refluxing acetonitrile, bromination using NBS gave the
benzylic bromide 17 in 96% yield. Esterification with
2-ethylhexanol using catalytic p-toluenesulfonic acid
in toluene and azeotropic removal of water gave the

PT
diester 16 in 93% yield, followed by etherification to
14 in 76% yield, with an overall yield of 68% yield
Scheme 4. Synthesis of DEHP-ester 18
over the three steps. Di(2-ethylhexyl) 4-(bromomethyl)
phthalate 16 served as a precursor to a second

RI
An attempt to prepare the symmetrical DEHP-diester
phthalate derivative with an ester linkage: DEHP-ester 19 by the reaction of benzylic bromide 16 with acety-
18. Benzylic bromide 16 was treated with propiolic lenedicarboxylic acid under similar conditions was not
acid and potassium carbonate in dimethylformamide successful (Scheme 5). Instead, monodecarboxylation

SC
for 15 minutes at 100 °C. The terminal alkyne DEHP- ensued under the basic conditions, to form the stabi-
ester 18 was obtained in 70% yield after purification lized acetylenic anion. Upon acidic workup, DEHP-
by silica gel column chromatography (Scheme 4). ester 18 was unexpectedly obtained.

U
AN
M
D
TE
EP

Scheme 5. Attempted Synthesis of Phthalate Derivative DEHP-Diester 19

C

Synthetic modification of commercial PVC results in cm-1 followed by the appearance of a peak at 1547 cm-1
polydisperse products, which are not amenable to easy is indicative of the formation of the triazole. In the 1H
AC

characterization by 1H NMR, 13C NMR, or mass spec- NMR spectrum, the benzylic proton of (1-azidoethyl)
troscopy. Therefore, (1-azidoethyl) benzene [27] was benzene shifted from δ 4.58 to 5.81 ppm in the triazole.
investigated as a model compound to confirm the viabil- The thermal Huisgen reaction is facilitated by electron
ity of azide/alkyne cycloaddition reactions with these poor substituents on the alkyne, which lower the alkyne
newly synthesized phthalate derivatives. For the unacti- HOMO. Using the electron-poor ester substituted al-
vated ether derivative 14, copper catalyzed cycloaddi- kyne, DEHP-ester 18 underwent thermal 1,3-dipolar
tion was utilized at room temperature to form the tria- cycloaddition with (1-azidoethyl) in benzene at 100 °C
zole 21. Thus cycloaddition of DEHP-ether 14 with ben- for 2 hours to give triazole 22 isolated in 34% yield as a
zyl azide 20 using catalytic copper iodide in a 6:1 mix- single regioisomer.
ture of tetrahydrofuran and water produced triazole 21 in
86% yield (Scheme 6). The disappearance of the termi-
nal alkyne peak at 2120 cm-1 and the azide peak at 2116

5
 ACCEPTED MANUSCRIPT

PT
RI
U SC
Scheme 6. Model Reactions: Copper Catalyzed and Thermal Huisgen Cycloadditions of Terminal Alkyne
DEHP Derivatives with a Small Molecule Azide
AN
M
D
TE
C EP
AC

Scheme 7. Attachment of DEHP-ether and DEHP-ester to Form Internally Plasticized PVC Triazoles with
Ether 9 and Ester 10 Tethers

6
 ACCEPTED MANUSCRIPT
These two complimentary conditions were then applied azide and the covalently plasticized PVC samples were
to modify PVC. Azide functional groups were incorpo- determined by using differential Scanning Calorimetry
rated into PVC by nucleophilic substitution of some of (DSC) and compared with non-covalent mixtures of 5%
the chlorines [27]. PVC with 5% or 15% substituted PVC-DEHP and 15% PVC-DEHP. To obtain the non-
azide was used in the cycloaddition reactions with covalent PVC-phthalate samples, a mixture of PVC (pu-
phthalates tethered to terminal alkynes. The degree of rified by the method of Rusen [31]) with either 5 wt%
azidation was determined by elemental analysis. The DEHP or 15 wt% DEHP was mechanically stirred at
cycloaddition of PVC-azide with DEHP-ether 14 using 120 °C for 4 h. The extent of Tg reduction in the pres-
copper iodide in 6:1 mixture of tetrahydrofuran and wa- ence of plasticizer is used as a parameter to assess the
ter gave a blue colored solid polymer after precipitation plasticizing efficiency. For each run, the calorimeter was
in methanol. To avoid coloration of the PVC, the copper equilibrated at 20 °C with a temperature ramp of 20

PT
iodide was replaced by copper sulfate/ascorbic acid to °C/min to 150 °C and then held at isothermal conditions
catalyze the cycloaddition of PVC-azide with DEHP- at 150 °C for 5 minutes before ending cycle 1. The sam-
ether 14. The reaction was carried out for 24 hours at ple was then cooled to 50 °C at a rate of 10 °C/min and
room temperature, resulting in the PVC bearing the held at 50 °C under isothermal conditions to end cycle 2.

RI
ether-tethered phthalate 9 as a white solid after precipi- For cycle 3, the sample was heated at a rate of 10
tation in methanol (Scheme 7). Thermal cycloaddition °C/min to 150 °C. The first cycle of heating is carried
of DEHP-ester 18 with the small molecule model (1- out to erase the pre-existing thermal history of the poly-

SC
azidoethyl) benzene (Scheme 6) in dimethylformamide mer. Mechanical and thermal properties of a polymer are
at 100 °C went to completion in 2 h. However, under affected by a number of variables such as chemical
these same thermal conditions, the reaction of 15% composition and molecular weight, as well as thermally
PVC-azide (with a six-fold excess of terminal alkyne 18 induced phenomena such as crystallization and physical

U
per azide) required 24 hours. Alternatively, the same aging, all of which contribute to the microstructure [32].
PVC triazole 10 was obtained in 24 hours at room tem- The covalent modification of PVC-DEHT, PVC-DEHP-
AN
perature when copper sulfate/ascorbic acid was used ether, PVC-DEHP-ester, and formation of the non-
with only 1.5 equivalent of alkyne 18 per azide (Scheme covalent DEHP samples were carried out under different
8). The conversion of azides into triazoles pendant to the reaction conditions, imparting different thermal histories
PVC was conveniently monitored by FTIR spectroscopy to the polymer samples. Thus by heating and rapid cool-
(Fig. 5). The shrinking of the diagnostic azide band at ing each of the PVC samples during cycles 1 and 2 of
M

2100-2000 cm-1, with concomitant appearance of the the DSC analysis, the thermal histories are erased. As
ester C=O band at 1725-1635 cm-1 and the C-N band at shown in Table 1, for most samples, two Tg values were
1550-1500 cm-1 is indicative of the formation of the tria- obtained in cycle 1, reflecting several polymeric re-
D

zoles tethered to phthalate esters. The glass transition gimes.

temperatures of unmodified PVC, 5% and 15% PVC-
TE

(a) (b)
C EP
AC

Fig. 5. Stacked FTIR Spectra: (a) PVC, 15% PVC-Azide, and 15% PVC-DEHP-ether Triazole (b) PVC, 15%
PVC-Azide, and 15% PVC-Azide-ester Triazole prepared by CuAAC

7
 ACCEPTED MANUSCRIPT
Sample Tg (°C) tion. The nucleophilic substitution of 15% of the chlo-
Cycle 1 Cycle 3 rine atoms of PVC with simple azide decreases the glass
transition temperature of the polymer from 82 °C to 75
Tg1 Tg2 Tg
°C. The Tgs were further reduced to 69 °C and 55 °C for
PVC (purified following Rusen’s 83 82 5% and 15% PVC-DEHP-ether 9, respectively (Figure
procedure)29 5). For 5% and 15% PVC-DEPH-ester 10, the Tgs were
5% PVC-Azide 84 84 observed at 69 °C and 60 °C, respectively (Figure 4). In
15% PVC-Azide 60 75 75 the case of PVC-DEHT 8, the glass transition tempera-
5% PVC-DEHT 6 61 61 ture increased from 61 °C for 5% PVC-DEHT to 65 °C
15% PVC-DEHT 6 64 65 for 15% PVC-DEHT. It is possible that direct attach-
ment of aromatic DEHT to the polymer chain imparts

PT
5% PVC-DEHP-ether 9 45 68 69
15% PVC-DEHP-ether 9 58 55 some crystallinity to the otherwise flexible PVC back-
bone, thus increasing the Tgs with increasing triazole
5% PVC-DEHP-ester 10 (Cu cat.) 58 71 69
substitution.

RI
15% PVC-DEHP-ester 10 (Cu cat.) 59 83 60
As described by Millán [33], certain regions of PVC
5% PVC-DEHP-ester 10 (thermal) 67 79 77 undergo nucleophilic substitution more readily than oth-
ers. These regions are associated with tacticity-specific

SC
15% PVC-DEHP-ester 10 (thermal) 31 61 60 microstructure within PVC. For the nucleophile sodium
benzenethiolate [34,35] at up to 20% substitution, Tg is
5% PVC-DEHP conventional 87 74
non-covalent mixture related to preferential substitution at the mmr triad of
15%PVC-DEHP conventional 83 75 isotactic sequences and the rmr triad located at the end

U
non-covalent mixture of syndiotactic sequences. During the early stages of
Table 1. Glass Transition Temperatures from Cycles nucleophilic substitution, the TGTG or the GTTG con-
AN
1 and 3 by DSC formation of the mmr isotactic tetrads are converted into
The polydispersity index of the commercial PVC used in nucleophile-substituted tetrads with a highly rigid TTTT
these experiments is 1.95, reflecting a realistic approach conformation, thus increasing the glass transition tem-
to internal plasticization on non-homogeneous PVC perature of PVC. When the mmr isotactic tetrads are
samples. One can envision that low molecular weight depleted, the less reactive rrm syndiotactic tetrads then
M

PVC chains might undergo azidation faster than the high take part in nucleophilic substitution. This results in the
molecular weight polymers, and certainly different triads shortening of the syndiotactic sequences, exchanging
of stereoisomers are expected to show different reactivi- them for sequences of reduced rigidity, and thus de-
D

ties to azide substitution within the PVC samples, giving creasing the glass transition temperature. At conversions
rise to multiple Tgs. An examination of the DSC ther- higher than 20%, neither mmr nor rrm triads are associ-
mograms of these internally plasticized PVC samples ated with isotactic or syndiotactic sequences. Therefore
TE

indicates that the Tg values decrease with increasing no significant change in the tacticity-induced micro-
substitution of the chlorine atoms in PVC with azide and structure is expected, and the results of variation of Tg
subsequently with tethered DEHP derivatives. Fig. 6 are due to the progressive substitution for chlorine atoms
clearly illustrates this trend: increasing the load of these by the nucleophile. The stereochemical structure of
EP

phthalate derivatives is reflected in enhanced plasticiza-

90
100
80
C

80 70
60
AC

60 50
Tg (°C)
Tg (°C)

40
40 30
20
20 10
0
0
0 5 10 15 20
0 5 10 15 20
% PVC Modification
% PVC Modification
Fig. 6. Variation of Glass Transition Temperatures of PVC-DEHP-ether 9 and PVC-DEHP-ester 10 with In-
creasing Internal Plasticizer Content (note: the dashed line is provided as an aid to the eye. It does not represent
a fit of the data.)
8
 ACCEPTED MANUSCRIPT
heterotactic, and syndiotactic tetrads [33,36] are clearly
shown in Fig 7. With increasing azidation, the isotactic
peaks get smaller with concurrent increase in the two
21% PVC-N3 downfield regions. At low levels of azidation, chlorines
from the isotactic tetrads undergo preferential substitu-
tion. The peaks associated with methine carbons bearing
azide come below 58.4 ppm for all three tetrads. After a
certain point there is no change in the isotactic region,
implying that nucleophilic substitution by azide is oc-
curring at the other tetrads (Fig. 8).
15% PVC-N3

PT
3. Conclusion

In summary, PVC was modified with pendant tria-

zoles bearing a derivative of the most common phthalate

RI
10% PVC-N3 plasticizer DEHP by two different flexible linkers: an
ether and an ester (PVC-DEHP-ether 9 and PVC-DEHP-
ester 10). The synthesis of these tethered phthalates was

SC
developed, and the glass transition temperatures meas-
ured to assess the plasticizing efficacy. The reduction in
glass transition temperature of PVC, from 83 °C to 55
5% PVC-N3 °C for 15% PVC-DEHP-ether 9, and to 60 °C for 15%

U
PVC-DEHP-ester 10, indicates successful plasticization
of PVC by covalently attaching phthalate derivatives.
AN
Comparison of glass transition temperatures shows that
PVC-DEHP-ether 9 is more effective in imparting plas-
Syndio Hetero
ticization than the ester analogue 10. This makes sense,
PVC Iso because the ether linkage is more flexible than the ester
linkage, which has several preferred conformations.
M

Both 15% covalent ether and ester linkages were more

effective than thermally incubating non-covalent DEHP
at 15% weight with PVC. However, even 15% PVC-
D

DEHP-ether showed only a moderate decline in Tg, indi-

cating that substitution higher than 15% of the chlorine
atoms of PVC will be required to achieve desirable plas-
TE

ticization for most commercial applications.

Fig. 7. 13C NMR Spectra of PVC and PVC substitut-
ed with Azide in DMF-d6 4. Experimental
EP

120 Commercial bulk polymerized PVC (Mw = 43,000)

was purchased from Sigma-Aldrich and was purified by
% unreacted isotactic Cl

100
following the procedure of Rusen [29]. PVC (5.003 g)
80 was dissolved in 60 mL of tetrahydrofuran (THF) at
C

room temperature, followed by precipitation with 180

60
mL of methanol. PVC-azide (5% and 15%) was pre-
AC

40 pared according to our previously published procedure

[27]. For 21% PVC-azide, 2.019 g of PVC and 2.006 g
20 of sodium azide were stirred in 20 mL of DMF at 60 °C
0 for 4 h. The % azidation of all PVC-N3 samples was
0 50 100 150 200 250 300 determined by elemental analysis. Tetrahydrofuran
Reaction Time (min) (Fisher Scientific) was dried over sodium and benzo-
phenone when anhydrous conditions were required. Ace-
Fig. 8. Participation of Isotactic Chlorines of PVC in tonitrile (Fisher Scientific) and toluene (Fisher Scien-
Nucleophilic Subsitution with Azides tific) were obtained from a PureSolv solvent purification
system manufactured by Innovative Technologies, Inc.
azide substituted PVC was studied by 13C NMR in deu-
when anhydrous conditions were required. Anhydrous
terated DMF-d6 (Fig. 7.). In unmodified PVC, the reso- silica gel (grade 60, 40 - 75 mesh, Sorbent Technolo-
nances from 57.5 to 60.0 ppm are those of the methine
gies) was activated by heating at 200 °C for 24 h under
carbons bearing chlorine atoms. The peaks of isotactic,
9
 ACCEPTED MANUSCRIPT
nitrogen and stored in a desiccator upon cooling. All Preparation of dimethyl 4-methylphthalate [35]. To a
other chemicals were used as received. The following stirred solution of dimethyl 4-methylcyclohexa-1,4-
chemicals were purchased from Sigma-Aldrich: sodium diene-1,2-dicarboxylate 11 (2.816 g, 13.39 mmol) in 50
azide (99.5%), 2-ethylhexanol (99%), sodium hydride mL of dichloromethane was added Dess-Martin perio-
(60% in mineral oil), N-bromosuccinamide (NBS), ben- dinane (5.682 g, 13.39 mmol) and stirred at room tem-
zoyl peroxide, propiolic acid (95%), and anhydrous di- perature for 14 h. The reaction mixture was concentrated
methyformamide. The following chemicals were pur- in vacuo, diluted with 100 mL of hexanes, and then fil-
chased from Acros Organics: dimethyl acetylenedicar- tered. The filtrate was concentrated in vacuo to give the
boxylate (98%), 4-methyl- title compound as a yellow oil (1.891 g, 67.76% yield).
phthalic anhydride (96%), Dess-Martin periodinane TLC: 75:25 hexanes/ethyl acetate, p-anisaldehyde stain,
(97%), and p-toluenesulfonic acid monohydrate (99%). Rf: 0.47.

PT
The following chemicals were purchased from Alfa Ae- 1
H NMR (500 MHz, CDCl3): δ 7.68 (d, J = 8.0 Hz, 1H),
sar: acetylenedicarboxylic acid, and dimethylacetylene 7.48 (d, J = 1.7 Hz, 1H), 7.33 (dd, d, J = 8.0, 1.7 Hz,
dicarboxylate (95%). Silica gel column chromatography 1H), 3.91 (s, 3H), 3.89 (s, 3H), 2.42 (s, 3H).
was performed on a Biotage Isolera™ Prime automated 13
C NMR (125 MHz, CDCl3, DEPT): δ 168.8 (C=O),

RI
flash purification system. NMR spectra were recorded at 167.9 (C=O), 142.2 (4°), 132.8 (4°), 131.5 (CH), 129.4
ambient temperature on a Varian 500 MHz spectrometer (CH), 129.3 (CH), 128.5 (4°), 52.7 (CH3), 52.5 (CH3),
or INOVO 500 MHz in CDCl3 as solvent unless other- 21.3 (CH3).

SC
wise noted. The spectra were recorded with the residual FTIR: 2959 (C-H stretch), 1728 (C=O stretch), 1463 (C-
CHCl3 peak (δ 7.27 ppm) as internal standard for 1H H scissoring), 1288 (C-O stretch) cm-1.
NMR and CDCl3 triplet (δ 77.27 ppm) for 13C NMR. Preparation of dimethyl 4-(bromomethyl)phthalate
FTIR spectra were recorded on a Perkin-Elmer spec- (12) [38]. To a stirred solution of dimethyl 4-

U
trometer as a neat film on a KBr cell. High resolution methylphthalate 11 (1.891 g, 9.082 mmol) and N-
mass spectra (HRMS) were recorded either on a bench- bromosuccinimide (1.617 g, 9.082 mmol) in 20 mL of
AN
top Mariner electrospray ionization time-of-flight benzene was added benzoyl peroxide (0.0391 g, 0.2738
(ESITOF) mass spectrometer or on LTQ Orbitrap. A TA mmol) and the reaction mixture was refluxed for 3 h.
Instruments DSC Q1000 was utilized to measure glass The reaction was allowed to cool to room temperature,
transition temperatures and other thermal endotherms. diluted with 100 mL of hexanes, and then filtered. The
All samples underwent a 5 min isotherm at 50 °C and filtrate was concentrated in vacuo. The resulting crude
M

were then heated to 150 °C at a heating rate of 20 yellow oil (3.124 g) was purified by Biotage gradient
°C/min followed by a 5 min isotherm before cooling to chromatography using hexanes/ethyl acetate as eluent to
50 °C at a cooling rate of 10 °C/min. Finally, samples give the title compound as a pale yellow oil (1.995 g,
D

were heated to 150 °C at a heating rate of 10 °C/min to 76.78% yield).

record thermal transitions. The typical sample masses TLC: 75:25 hexanes/ethyl acetate, p-anisaldehyde stain,
were approximately 8 mg, which were sealed in alumi- Rf: 0.42.
TE

num hermetic pans. 1

H NMR (500 MHz, CDCl3): δ 7.73 (d, J = 1.0 Hz, 1H),
Preparation of dimethyl 4-methylcyclohexa-1,4- 7.70 (d, J = 8.0 Hz, 1H), 7.55 (dd, J = 8.0 Hz, 1.0 Hz,
diene-1,2-dicarboxylate (11) [37]. Following the pro- 1H), 4.48 (s, 2H), 3.91 (s, 3H), 3.89 (s, 3H).
cedure of Smit et al [28] a mixture of dimethylacetylene 13
C NMR (125 MHz, CDCl3, DEPT): δ 167.7 (C=O),
EP

dicarboxylate (3.468 g, 24.40 mmol), isoprene (14.7 167.6 (C=O), 141.2 (4°), 132.7 (4°), 131.7 (4°), 131.7
mL, 146 mmol), and activated silica gel (40.13 g) was (CH), 129.7 (CH), 129.5 (CH), 52.8 (CH3), 52.7 (CH3),
stirred at room temperature for 18 h. The reaction flask 31.3 (CH2).
was equipped with a Findenser™ to minimize the evap- FTIR: 2953 (C-H stretch), 1728 (C=O stretch), 1435 (C-
C

oration of isoprene. Diethyl ether (100 mL) was added H scissoring), 1294 (C-O stretch) cm-1.
to the reaction mixture, and then filtered. The filtrate Preparation of dimethyl 4-((prop-2-yn-1-yloxy)-
AC

was concentrated in vacuo to give the title compound as methyl)phthalate (13). To a stirred solution of dimethyl
a yellow oil (4.932 g, 96.14% yield). 4-(bromomethyl)phthalate 12 (1.228 g, 4.294 mmol) and
TLC: 75:25 hexanes/ethyl acetate, p-anisaldehyde stain, propargyl alcohol (0.4798 g, 8.564 mmol) in 20 mL of
Rf: 0.50. anhydrous tetrahydrofuran was added sodium hy-
1
H NMR (500 MHz, CDCl3): δ 5.36 – 5.34 (m, 1H), dride(0.0961 g, 1.713 mmol, 60% suspension in mineral
3.74 (s, 3H), 3.73 (s, 3H), 2.98 – 2.92 (m, 2H), 2.87 – oil) in portions over 10 minutes at 0 °C. The reaction
2.82 (m, 2H), 1.67 (s, 3H). mixture was stirred for 2 h and then quenched with 10
13
C NMR (125 MHz, CDCl3, DEPT): δ 168.7 (C=O), mL of saturated ammonium chloride solution. The or-
168.5 (C=O), 132.9 (4°), 132.4 (4°), 129.7 (4°), 116.7 ganic layer was separated and the aqueous layer was
(CH), 52.2 (OCH3), 32.1 (CH2), 28.6 (CH2), 22.5 (CH3). extracted three times with 50 mL of ethyl acetate. The
FTIR: 2953 (C-H stretch), 1727 (C=O stretch), 1655 combined organic layer was washed two times with 20
(C=C stretch), 1435 (C-H scissoring), 1250 (C-O mL of brine, dried over MgSO4 and concentrated in
stretch) cm-1. vacuo. The resulting red oil (2.325 g) was purified by
10
 ACCEPTED MANUSCRIPT
silica gel column chromatography with 75:25 hex- 4.746 mmol), anhydrous silica gel (20.13 g), and iso-
anes/ethyl acetate as eluent to give the title compound as prene (5.8 mL, 58 mmol) was stirred at room tempera-
a pale yellow oil (0.5515 g, 48.97% yield). ture for 18 h. The reaction flask was equipped with a
TLC: 75:25 hexanes/ethyl acetate, p-anisaldehyde stain, Findenser™ to minimize evaporation of isoprene. Di-
Rf: 0.33. chloromethane (200 mL) was added to the reaction mix-
1
H NMR (500 MHz, CDCl3): δ 7.74 (d, J = 7.9 Hz, 1H), ture, and then filtered. The filtrate was concentrated in
7.70 (d, J = 1.5 Hz, 1H), 7.53 (dd, J = 7.9, 1.5 Hz, 1H), vacuo and bubbled with air for 3 d to give the title com-
4.67 (s, 2H), 4.21 (d, J = 2.5 Hz, 2H), 3.41 (s, 3H), 3.40 pound as a yellow oil (2.011, 96.14% yield).
(s, 3H), 2.76 (t, J = 2.5 Hz, 1H). TLC: 90:10 hexanes/ethyl acetate, p-anisaldehyde stain,
13
C NMR (125 MHz, CDCl3, DEPT): δ 168.2 (C=O), Rf: 0.66.
167.8 (C=O), 141.1 (4°), 132.5 (4°), 131.1 (4°), 130.0
1
H NMR (500 MHz, CDCl3, two diastereomers): δ 7.65

PT
(CH), 129.3 (CH), 127.9 (CH), 79.2 (CH), 75.3 (4°), (d, J = 8.0 Hz, 1H), 7.44 (d, J = 1.7 Hz, 1H), 7.31 (dd, J
70.4 (CH2), 57.7 (CH2), 52.8 (CH3), 52.7 (CH3). = 8.0, 1.7 Hz, 1H), 4.25 – 4.11 (m, 4H), 2.42 (s, 3H),
FTIR: 2931 (aliphatic C-H stretch), 2120 (alkyne C-C 1.75 – 1.49 (m, 2H), 1.51 – 1.18 (m, 16H), 1.02 – 0.77
(m, 12H).

RI
stretch), 1727 (C=O stretch), 1462 (aromatic C=C
13
stretch), 1287 (C-O stretch) cm-1 C NMR (125 MHz, CDCl3, DEPT, two diastereomers):
Preparation of bis(2-ethylhexyl) 4-((prop-2-yn-1- δ 168.5 (C=O), 167.5 (C=O), 141.9 (4°), 133.3 (4°),
yloxy)methyl)phthalate (14). To a stirred solution of 2- 131.3 (CH), 129.9 (CH), 129.3 (4°), 67.9 (CH2), 67.6

SC
ethylhexanol (0.4398 g, 3.377 mmol) in 5 mL of anhy- (CH2), 38.8 (CH), 38.7 (CH), 30.4 (CH2), 30.2 (CH2),
drous tetrahydrofuran was added sodium hydride 28.8 (CH2), 28.7 (CH2), 23.7 (CH2), 23.5 (CH2), 21.3
(0.3402 g, 7.091 mmol, 60% suspension in mineral oil) (CH3), 14.1 (CH3), 11.0 (CH3).
at room temperature and stirred for 5 minutes. A solu- FTIR: 2953 (C-H stretch), 1728 (C=O stretch), 1435 (C-

U
tion of dimethyl 4-((prop-2-yn-1-yloxy)methyl) H scissoring), 1294 (C-O stretch) cm-1.
phthalate 13 (0.4428 g, 1.688 mmol) in 5 mL of anhy- Preparation of bis(2-ethylhexyl) 4-(bromomethyl)-
AN
drous tetrahydrofuran was added at room temperature, phthalate (16). To a stirred solution of bis(2-ethylhexyl)
and stirred for 1 h. The reaction mixture was cooled to 0 4-methylphthalate 15 (0.3681 g, 0.9098 mmol) and N-
°C, and then quenched with 3 mL of saturated ammoni- bromosucinimide (0.1943 g, 0.0273 mmol) in 10 mL of
um chloride solution. The organic layer was separated benzene was added benzoyl peroxide (0.0039 g, 1.991
and the aqueous layer was extracted three times with 10 mmol) at room temperature. The reaction mixture was
M

mL of chloroform. The combined organic layer was refluxed for 3 d using a Dean-Stark apparatus. The reac-
washed two times with 10 mL of brine, dried over tion mixture was concentrated in vacuo to evaporate
MgSO4 and concentrated in vacuo. The resulting red oil benzene. The resulting yellow oil (0.2221 g) was puri
D

(0.8178 g) was purified by silica gel column chromatog- fied by Biotage gradient chromatography using hex-
raphy with 75:25 hexanes/ethyl acetate as eluent, to give anes/ethyl acetate as eluent, to give the title compound
the title compound as a pale yellow oil (0.2414 g, as a pale yellow oil (0.1511 g, 32.29% yield).
TE

31.18% yield). TLC: 90:10 hexanes/ethyl acetate, p-anisaldehyde stain,

TLC: 75:25 hexanes/ethyl acetate, p-anisaldehyde, Rf: Rf: 0.40.
0.77. 1
H NMR (500 MHz, CDCl3, two diastereomers): δ 7.69
1
H NMR (500 MHz, CDCl3, two diastereomers): δ 7.72 (d, J = 1.8 Hz, 1H), 7.58 (d, J = 7.5 Hz, 1H), 7.55 (dd,
EP

(d, J = 7.9 Hz, 1H), 7.66 (d, J = 1.7 Hz, 1H), 7.52 (dd, J J= 7.5, 1.8 Hz, 1H), 4.49 (s, 2H), 4.29 - 4.12 (m, 4H),
= 7.9, 1.7 Hz, 1H), 4.67 (s, 2H), 4.31 - 4.11 (m, 6H), 1.68 (m, 2H), 1.48 - 1.18 (m, 16H), 0.81 - 0.91 (m,
2.49 (t, J = 2.5 Hz, 1H), 1.68 (m, 2H), 1.47 - 1.20 (m, 12H).
13
16H), 0.99 - 0.81 (m, 12H). C NMR (125 MHz, CDCl3, DEPT, two diastere-
C

13
C NMR (125 MHz, CDCl3, DEPT, two diastere- omers): δ (167.8 (C=O), 167.7 (C=O), 141.4 (4°), 133.7
omers): δ 167.9 (C=O), 167.5 (C=O), 141.1 (4°), 133.1 (4°), 132.6 (4°), 131.9 (CH), 129.9 (CH), 129.8 (CH),
AC

(4°), 131.6 (4°), 129.9 (CH), 129.3 (CH), 127.9 (CH), 68.9 (CH2), 68.7 (CH2), 39.12 (CH), 31.9 (CH2), 30.8
79.2 (CH), 75.2 (4°), 70.4 (CH2), 68.3 (CH2), 68.2 (CH2), 29.3 (CH2), 24.2 (CH2), 23.4 (CH2), 14.5 (CH3),
(CH2), 57.6 (CH2), 38.8 (CH), 31.9 (CH2), 30.4 (CH2), 11.4 (CH3).
28.9 (CH2), 23.7 (CH2), 23.0 (CH2), 14.1 (CH3), 11.0 FTIR: 2930 (C-H stretch), 1728 (C=O stretch), 1463 (C-
(CH3). H scissoring), 1288 (C-O stretch) cm-1.
FTIR: 2931 (aliphatic C-H stretch), 2120 (alkyne C-C HRMS: calcd. for C29H35BrO4 [M-H]: 481.1958: found
stretch), 1727 (C=O stretch), 1462 (aromatic C=C 481.1955.
stretch), 1287 (C-O stretch) cm-1. Preparation of 4-bromomethylphthalic anhydride
HRMS: calcd. for C28H42O5 [M+H]+: 459.3105: found (17). To a stirred solution of 4-methylphthalic anhydride
459.3075. and N-bromosuccinimide (5.601 g, 31.47 mmol) in
Preparation of bis(2-ethylhexyl) 4-methylphthalate 100 mL of acetonitrile was added dibenzoyl peroxide
(15). Following the procedure of Smit et al. [30] a mix- (0.1345 g, 0.9441 mmol) at room temperature. The reac-
ture of 2-ethylhexylacetylene dicarboxylate (1.739 g, tion mixture was refluxed for 24 h. The reaction mixture
11
 ACCEPTED MANUSCRIPT

was allowed to cool to room temperature and 20 mL of The aqueous layer was extracted three times with 100
saturated sodium bisulfite solution was added. The reac- mL of chloroform. The combined organic layer was
tion mixture was concentrated in vacuo. The aqueous washed three times with 100 mL of brine, dried over
layer was extracted three times with 100 mL of diethyl MgSO4 and concentrated in vacuo. The resulting red oil
ether. The combined organic layer was washed with 100 (4.123 g) was purified by silica gel column chromatog-
mL of brine, dried over MgSO4, and then concentrated raphy using 90:10 hexanes/ethyl acetate as eluent, to
in vacuo. The resulting yellow viscous oil (7.027 g, give the title compound as a pale yellow oil (2.985 g,
92.64%) was used in the next step without purification. 70.63% yield).
1
H NMR (500 MHz, CDCl3): δ 8.02 (d, J = 1.5 Hz, 1H), TLC: 75:25 hexanes/ethyl acetate, p-anisaldehyde stain,
7.99 (d, J = 7.9 Hz, 1H), 7.92 (dd, J = 7.8, 1.5 Hz, 1H), Rf: 0.24.

PT
4.59 (s, 2H). 1
H NMR (500 MHz, CDCl3, two diastereomers): δ 7.72
13
C NMR (125 MHz, CDCl3, DEPT): δ 162.2 (C=O), (d, J = 8.0 Hz, 1H), 7.69 (s, 1H), 7.53 (m, 1H), 5.26 (s,
162.1 (C=O), 146.9 (4°), 136.9 (4°), 136.8 (CH), 126.2 2H), 4.21 (m, 4H), 2.94 (s, 1H), 1.75 – 1.60 (m, 2H),
1.36 (m, 16H), 1.02 – 0.79 (m, 12H).

RI
(CH), 125.9 (CH), 125.5 (4°), 30.5 (CH2).
13
FTIR: 2953 (C-H stretch), 1701 (C=O stretch, anhy- C NMR (125 MHz, CDCl3, DEPT, two diastere-
dride), 1423 (C-H scissoring), 1289 (C-O stretch) cm-1. omers): δ 167.3 (C=O), 167.1 (C=O), 152.2 (C=O),
HRMS: calcd. for C9H5BrO2 [M+H]+: 240.9495: found 137.7 (4°), 132.9 (4°), 132.4 (4°), 130.3 (CH), 129.3

SC
240.9476. (CH), 128.3 (CH), 75.7 (CH), 74.1 (4°), 68.3 (CH2),
Preparation of bis(2-ethylhexyl) 4-(bromomethyl)- 68.2 (CH2), 66.4 (CH2), 38.7 (CH), 38.6 (CH), 30.4
phthalate by anhydride opening (16). To a stirred so- (CH2), 30.3 (CH2), 28.9 (CH2), 23.7 (CH2), 22.9 (CH2),
lution of 4-bromomethyl-phthalic anhydride 17 (7.997 g, 14.0 (CH3), 10.9 (CH3).

U
33.18 mmol) and 2-ethylhexanol (8.641 g, 66.35 mmol) IR (neat): 2959 (aliphatic C-H stretch), 2020 (alkyne C-
in 50 mL of toluene was added p-toluenesulfonic acid C stretch), 1725 (C=O stretch), 1461 (aromatic C=C
stretch), 1286 (C-O stretch) cm-1.
AN
(0.3786 g, 1.991 mmol). The reaction mixture was re-
fluxed for 2 h using a Dean-Stark apparatus, then cooled HRMS: calcd. for C28H41O6 [M+H]+: 473.2898: found
and concentrated in vacuo. The resulting yellow oil 473.2875.
(0.2221 g) was purified by silica gel column chromatog- Preparation of bis(2-ethylhexyl) 4-(((1-(1-phenyl-
raphy using 90:10 hexanes/ethyl acetate as eluent, to ethyl)-1H-1,2,3-triazol-4-yl)methoxy)methyl)-
M

give the title compound as a pale yellow oil (12.12 g, phthalate (21). To a stirred solution of bis(2-ethylhexyl)
75.17% yield). 4-((prop-2-yn-1-yloxy)methyl)phthalate 14 (0.0876 g,
Preparation of bis(2-ethylhexyl) 4-((prop-2-yn-1- 0.1910 mmol) and 1-phenylethyl azide (0.0637 g,
D

yloxy)methyl)phthalate (14). To a stirred solution of 0.4331 mmol) in 10 mL of 6:1 THF:H2O was added
bis(2-ethylhexyl) 4-(bromomethyl)phthalate 16 (3.084 g, copper iodide (0.0521 g, 0.2736 mmol) at room temper-
6.391 mmol) and propargyl alcohol (0.4297 g, 7.669 ature and stirred for 18 h. The reaction mixture was di-
TE

mmol) in 60 mL of dry tetrahydrofuran was added sodi- luted with 50 mL of diethyl ether. The organic layer was
um hydride (0.6282 g, 26.18 mmol, 60% suspension in separated and washed three times with 10 mL of saturat-
mineral oil) in portions over 10 minutes at 0 °C. The ed sodium carbonate solution, one time with 10 mL of
reaction mixture was warmed to room temperature and brine, dried over MgSO4 and concentrated in vacuo to
EP

stirred for 22 h, then cooled to 0 °C and quenched with give a yellow oil (0.1041 g, 86.03% yield).
10 mL of saturated ammonium chloride solution. The TLC: 75:25 hexanes/ethyl acetate, p-anisaldehyde stain,
organic layer was separated and the aqueous layer was Rf: 0.19.
extracted three times with 50 mL of ethyl acetate. The 1
H NMR (500 MHz, CDCl3, multiple diastereomers): δ
C

combined organic layer was washed two times with 20 7.70 (d, J = 8.0 Hz, 1H), 7.63 (s, 1H), 7.49 (d, J = 8.0
mL of brine, dried over MgSO4 and concentrated in Hz, 1H), 7.45 (s, 1H), 7.38 – 7.10 (m, 3H), 7.29 – 7.26
AC

vacuo. The resulting red oil (3.325 g) was purified by (m, 2H), 5.80 (q, J = 7.0 Hz, 1H), 4.68 (s, 2H), 4.64 (s,
silica gel column chromatography with 90:10 hex- 2H), 4.30 – 4.09 (m, 4H), 1.97 (d, J = 7.0 Hz, 3H), 1.67
anes/ethyl acetate as eluent, to give the title compound (m, 2H), 1.47 – 1.20 (m, 16H), 0.90 (m, 12H).
13
as a pale yellow oil (2.111 g, 72.03% yield). C NMR (125 MHz, CDCl3, DEPT, multiple diastere-
Preparation of bis(2-ethylhexyl) 4-((propioloyloxy)- omers): δ 168.1 (C=O), 167.5 (C=O), 144.8 (4°), 141.6
methyl)phthalate (18). To a stirred solution of bis(2- (4°), 139.6 (4°), 133.2 (4°), 131.4 (4°), 129.8(CH),
ethylhexyl) 4-(bromomethyl)phthalate 16 (4.311 g, 129.3 (CH), 128.9 (CH), 128.7 (CH), 127.7 (CH), 126.7
8.935 mmol) and propiolic acid (0.6706 g, 8.935 mmol) (CH), 121.5 (CH), 71.5 (CH2), 68.3 (CH2), 68.2 (CH2),
in 10 mL of anhydrous dimethylformamide was added 64.2 (CH2), 60.4 (CH), 38.8 (CH), 38.7 (CH2), 30.4
potassium carbonate (3.705 g, 26.81 mmol) at room (CH2), 30.3 (CH2), 29.0 (CH2), 23.8 (CH2), 23.7 (CH2),
temperature. The reaction mixture was heated to 100 °C 23.0 (CH2), 21.6 (CH3), 14.1 (CH3), 11.0 (CH3).
and stirred for 15 minutes, then allowed to come to
room temperature and diluted with 100 mL of water.
12
 ACCEPTED MANUSCRIPT
IR (neat): 2959 (aliphatic C-H stretch), 1726 (C=O (1.031 g, 15.16 mmol) and DEHP-ester 18 (0.5338 g,
stretch), 1576 (C-N stretch), 1458 (aromatic C=C 1.129 mmol) in 70 mL of 6:1, THF:H2O was added
stretch), 1286 (C-O stretch) cm-1. CuSO4•5H2O (0.5673 g, 2.272 mmol) and ascorbic acid
HRMS: calcd. for C36H51N3O5 [M+H]+: 606.3902: found (0.6783 g, 3.851 mmol). The reaction mixture was
606.3848. stirred at room temperature for 24 h, and then filtered.
Preparation of bis(2-ethylhexyl) 4-(((1-(1-phenyl- The filtrate was poured into 200 mL of methanol and
ethyl)-1H-1,2,3-triazole-4-carbonyl)oxy)methyl)- filtered. The cake was washed one time with 25 mL of
phthalate (22). A solution of bis(2-ethylhexyl) 4- water, one time with 25 mL of methanol and dried to
((propioloyloxy)methyl)phthalate 18 (0.4865 g, 0.1029 give yellow solid (1.012 g). The cycloaddition of 15%
mmol) and 1-phenylethyl azide (0.1514 g, 0.1029 PVC-azide sample was carried out in a similar fashion
mmol) in 3 mL of dimethylformamide was stirred at 100 with three times more of DEHP-ester 18.

PT
°C for 2 h. The reaction mixture was allowed to come to IR (neat): 2959 (aliphatic C-H stretch), 1725 (C=O
room temperature, and then diluted with 20 mL of di- stretch), 1578 (C-N stretch), 1459 (aromatic C=C
chloromethane. The organic layer was washed three stretch), 1287 (C-O stretch) cm-1.
times with 10 mL of brine, dried over MgSO4, and con- Preparation of 5% PVC-DEHP-ester (10) by thermal

RI
centrated in vacuo. The resulting yellow oil (0.5432 g) route. To a stirred solution of 5% PVC-azide (0.3479 g,
was purified by silica gel column chromatography using 5.116 mmol) in 10 mL of dimethylformamide was add-
3:1 hexanes/ethyl acetate as eluent, to give the title ed DEHP-ester 18 (0.7254 g, 1.535 mmol) and stirred at

SC
compound as a colorless oil (0.2155 g, 33.78% yield). 100 °C for 24 h. The reaction mixture was allowed to
TLC: 75:25 hexanes/ethyl acetate, p-anisaldehyde stain, cool to room temperature and then poured into 100 mL
Rf: 0.24. of methanol, and filtered. The cake was washed three
1
H NMR (500 MHz, CDCl3, multiple diastereomers): δ times with 20 mL of methanol and dried to give white

U
7.96 (s, 1H), 7.75 – 7.62 (m, 2H), 7.57 (d, J = 8.0 Hz, solid (0.3256 g). The cycloaddition of 15% PVC-azide
1H), 7.40 – 7.28 (m, 3H), 7.28-7.17 (m, 2H), 5.84 (q, J sample was carried out in a similar fashion with three
AN
= 7.1 Hz, 1H), 5.37 (s, 2H), 4.22 - 4.10 (m, 4H), 1.96 (d, times more of DEHP-ester 18.
J = 7.1 Hz, 3H), 1.65 - 1.58 (m, 2H), 1.45 – 1.15 (m,
16H), 0.94 - 0.76 (m, 12H). Associated content
13
C NMR (125 MHz, CDCl3, DEPT, multiple diastere-
1
omers): δ 167.5 (C=O), 167.2 (C=O), 160.3 (C=O), H NMR, 13C NMR, DEPT, FTIR, and DSC thermograms.
M

139.4 (4°), 138.8 (4°), 138.7 (4°), 132.9 (4°), 132.1 (4°), The Supporting Information is available free of charge on
130.5 (CH), 129.2 (CH), 129.1 (CH), 128.9 (CH), 128.4 the ACS Publications website.
(CH), 126.6 (CH), 126.5 (CH), 68.3 (CH2), 68.1 (CH2),
D

65.4 (CH2), 60.8 (CH), 38.7 (CH), 38.6 (CH), 30.3

(CH2), 30.2 (CH2), 28.9 (CH2), 23.7 (CH2), 23.6 (CH2), Author information
22.9 (CH2), 21.2 (CH3), 14.1 (CH3), 11.0 (CH3).
TE

Corresponding Author
IR (neat): 2959 (aliphatic C-H stretch), 1726 (C=O Prof. Rebecca Braslau
stretch), 1541 (C-N stretch), 1458 (aromatic C=C Department of Chemistry and Biochemistry
stretch), 1286 (C-O stretch) cm-1. University of California, Santa Cruz,
HRMS: calcd. for C36H49N3O6 [M+H]+: 620.3695: found
EP

Santa Cruz, California, 95064, USA.

620.3644. Telephone: (831) 459-3087
Preparation of 5% PVC-DEHP-ether (9). To a stirred Email: [email protected]
solution of 5% PVC-azide (1.511 g, 22.22 mmol) and
DEHP-ether 14 (0.7642 g, 1.667 mmol) in 70 mL of 6:1, Funding Source
C

THF:H2O was added CuSO4•5H2O (0.5548 g, 2.272 We gratefully acknowledge research funding from the
mmol) and ascorbic acid (0.6783 g, 5.677 mmol). The NSF DMR-1404550, and the NSF CHE 1427922 for
AC

reaction mixture was stirred at room temperature for 24 MS instrumentation.

h, and then filtered. The filtrate was poured into 200 mL
of methanol. The precipitated solid was filtered, washed Acknowledgment
one time with 25 mL of water, one time with 25 mL of The authors thank Travis Smith from California Poly-
methanol and dried to give yellow solid (1.236 g). The technic State University, San Luis Obispo for his help
cycloaddition of 15% PVC-azide sample was carried out with Differential Scanning Calorimetry.
in a similar fashion with three times more of DEHP-
ether 14.
IR (neat): 2959 (aliphatic C-H stretch), 1723 (C=O References
stretch), 1541 (C-N stretch), 1462 (aromatic C=C
stretch), 1284 (C-O stretch) cm-1. [1] Ertl, J.; Brock, T.; Kufner, T.; Mieden, O.;
Preparation of 5% PVC-DEHP-ester (10) by Cu cat- Proessdorf, W.; Vogel, E. Back to Square One: Polyvi-
alyzed route. To a stirred solution of 5% PVC-azide
13
 ACCEPTED MANUSCRIPT
nylchloride (PVC). Kunststoffe International 10 (2013) [14] Fierens, T.; Van Holderbeke, M.; Willems, H.;
14-19. De Henauw, S.; Sioen, I. Transfer of eight phthalates
[2] Tullo, A. H. Plasticizer makers want a piece of through the milk chain - A case study. Environ. Int. 51
the phthalates pie. Chem. Eng. News 93 (25) (2015) 16- (2013) 1-7.
18. [15] Fromme, H.; Gruber, L.; Seckin, E.; Raab, U.;
[3] Shapiro, G. D.; Dodds, L.; Arbuckle, T. E.; Zimmermann, S.; Kiranoglu, M.; Schlummer, M.;
Ashley-Martin, J.; Fraser, W.; Fisher, M.; Taback, S.; Schwegler, U.; Smolic, S.; Volkel, W. Phthalates and
Keely, E.; Bouchard, M. F.; Monnier, P.; Dallaire, R.; their metabolites in breast milk--results from the Bavari-
Morisset, A. S.; Ettinger, A. S. Exposure to phthalates, an Monitoring of Breast Milk (BAMBI). Environ. Int.
bisphenol A and metals in pregnancy and the association 37 (4) (2011) 715-722.
with impaired glucose tolerance and gestational diabetes [16] Hines, E. P.; Calatat, A. M.; Silva, M. J.;

PT
mellitus: The MIREC study. Environ. Int. 83 (2015) 63- Mendola, P.; Fenton, S. E. Concentrations of Phthalate
71. Metabolites in Milk, Urine, Saliva, and Serum of Lactat-
[4] Schaedlich, K.; Schmidt, J. S.; Kwong, W. Y.; ing North Carolina Women. Environ. Health Perspect.
Sinclair, K. D.; Kurz, R.; Jahnke, H. G.; Fischer, B., J. 117 (1) (2009) 86-92.

RI
Impact of di-ethylhexylphthalate exposure on metabolic [17] Wan, H. T.; Leung, P. Y.; Zhao, Y. G.; Wei, X.;
programming in P19 ECC-derived cardiomyocytes. Wong, M. H.; Wong, C. K. Blood plasma concentrations
Appl. Toxicol. 35 (7) (2015) 861-869. of endocrine disrupting chemicals in Hong Kong popu-

SC
[5] Golshan, M.; Hatef, A.; Socha, M.; Milla, S.; lations. J. Hazard. Mater. 261 (2013) 763-769.
Butts, I. A.; Carnevali, O.; Rodina, M.; Sokolowska- [18] Bernard, L.; Cueff, R.; Breysse, C.; Decaudin,
Mikolajczyk, M.; Fontaine, P.; Linhart, O.; Alavi, S. M. B.; Sautou, V. Migrability of PVC plasticizers from
Di-(2-ethylhexyl)-phthalate disrupts pituitary and testic- medical devices into a simulant of infused solutions.

U
ular hormonal functions to reduce sperm quality in ma- Int. J. Pharm. 485 (1-2) (2015) 341-347.
ture goldfish. Aquat. Toxicol. 163 (2015) 16-26. [19] Ji, L.; Liao, Q.; Wu, L.; Lv, W.; Yang, M.;
AN
[6] Liu, T.; Li, N.; Zhu, J.; Yu, G.; Guo, K.; Zhou, Wan, L. Migration of 16 phthalic acid esters from plastic
L.; Zheng, D.; Qu, X.; Huang, J.; Chen, X.; Wang, S.; drug packaging to drugs by GC-MS. Anal Methods 5
Ye, L. Effects of di-(2-ethylhexyl) phthalate on the hy- (11) (2013) 2827-2834.
pothalamus-pituitary-ovarian axis in adult female rats. [20] Hwang, H. M.; Park, E. K.; Young, T. M.;
Reprod. Toxicol. 46 (2014) 141-147. Hammock, B. D. Occurrence of endocrine-disrupting
M

[7] Weiss, B., Endocrine disruptors as a threat to chemicals in indoor dust. Sci. Total Environ. 404 (1)
neurological function. J. Neurosci. 305 (1-2) (2011)11- (2008) 26-35.
21. [21] Mijangos, C.; Michel, A.; Martin, A. Fonction-
D

[8] North, M. L.; Takaro, T. K.; Diamond, M. L.; nalisation du polychlorure de vinyle. Eur. Polym. J. 22
Ellis, A. K. Effects of phthalates on the development (5) (1986) 417-421.
and expression of allergic disease and asthma. Annals of [22] Navarro, R.; Perrino, M. P.; Tardajos, M. G.;
TE

Allergy Asthma And Immunology 112 (6) (2014) 496- Reinecke, H., Phthalate plasticizers covalently bound to
502. pvc: plasticization with suppressed migration.
[9] Zhang, X.; Chen, Z. Observing phthalate leach- Macromolecules 43 (5) (2010) 2377-2381.
ing from plasticized polymer films at the molecular [23] Navarro, R.; Perrino, M. P.; Garcia, C.; Elvira,
EP

level. Langmuir 30 (17) (2014) 4933-4944. C.; Gallardo, A.; Reinecke, H., Opening New Gates for
[10] Wang, J.; Chen, G.; Christie, P.; Zhang, M.; the Modification of PVC or Other PVC Derivatives:
Luo, Y.; Teng, Y. Occurrence and risk assessment of Synthetic Strategies for the Covalent Binding of
phthalate esters (PAEs) in vegetables and soils of subur- Molecules to PVC. Polymers 8 (4) (2016)
C

ban plastic film greenhouses. Sci. Total Environ. 523 doi:10.3390/polym8040152.

(2015) 129-137. [24] Navarro, R.; Perrino, M. P.; Garcia, C.; Elvira,
AC

[11] Al-Saleh, I.; Shinwari, N.; Alsabbaheen, A. C.; Gallardo, A.; Reinecke, H., Highly flexible PVC
Phthalates residues in plastic bottled waters. J. Toxicol. materials without plasticizer migration as obtained by
Sci. 36 (4) (2011) 469-478. efficient one-pot procedure using trichlorotriazine
[12] Sungur, S.; Okur, R.; Turgut, F. H.; Ustun, I.; chemistry. Macromolecules 49 (6) (2016) 2224-2227.
Gokce, C. Migrated phthalate levels into edible oils. [25] Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.;
Food Addit. Contam. Part B-Surveillance 8 (3) (2015) Sharpless, K. B. A stepwise Huisgen cycloaddition
190-194. process: Copper(I)-catalyzed regioselective "ligation" of
[13] Xu, Q.; Yin, X.; Wang, M.; Wang, H.; Zhang, azides and terminal alkynes. Angew. Chem. Int. Ed. 41
N.; Shen, Y.; Xu, S.; Zhang, L.; Gu, Z. Analysis of (14) (2002) 2596-2599.
phthalate migration from plastic containers to packaged [26] Tornoe, C. W.; Christensen, C.; Meldal, M.,
cooking oil and mineral water. J. Agric. Food Chem. 58 Peptidotriazoles on solid phase: 1,2,3-triazoles by
(21) (2010) 11311-11317. regiospecific copper(I)-catalyzed 1,3-dipolar cyclo-

14
 ACCEPTED MANUSCRIPT
additions of terminal alkynes to azides. J. Org. Chem.
67 (9) (2002) 3057-3064.
[27] Earla, A.; Braslau, R. Covalently linked plasti-
cizers: triazole analogues of phthalate plasticizers pre-
pared by mild copper-free "click" reactions with azide-
functionalized PVC. Macromol. Rapid Commun. 35 (6)
(2014) 666-671.
[28] Demirci, G.; Tasdelen, M. A. Synthesis and
characterization of graft copolymers by photoinduced
CuAAC click chemistry. Eur. Polym. J. 66 (2015) 282-
289.

PT
[29] Yang, P.; Yan, J.; Sun, H.; Fan, H.; Chen, Y.;
Wang, F.; Shi, B. Novel environmentally sustainable
cardanol-based plasticizer covalently bound to PVC via
click chemistry: synthesis and properties. RSC Advances

RI
5 (22) (2015) 16980-16985.
[30] Veselovsky, V. V.; Gybin, A. S.; Lozanova, A.
V.; Moiseenkov, A. M.; Smit, W. A.; Caple, R. Dra-

SC
matic acceleration of the Diels-Alder reaction by adsorp-
tion on chromatography adsorbents. Tetrahedron Lett.
29 (2) (1988)175-178.
[31] Rusen, E.; Marculescu, B.; Butac, L.; Preda, N.;

U
Mihut, L. The Synthesis and Characterization of Poly
Vinyl Chloride Chemically Modified with C60. Fuller.
AN
Nanotub. Car. N. 16 (3) (2008)178-185.
[32] Yarahmadi, N.; Jakubowicz, I.; Hjertberg, T.
The effects of heat treatment and ageing on the mechan-
ical properties of rigid PVC. Polym. Degrad. Stab. 82
(1) (2003) 59-72.
M

[33] Millan, J.; Guarrotxena, N.; Tiemblo, P.; M, G.-

E.; Martinez, G. Tacticity induced molecular microstruc-
ture dependence of physical properties of polymers-
D

fundamentals and overview of some tentative correla-

tions. Eur. Polym. J. 34 (5-6) (1998) 833-839.
[34] Tiemblo, P.; Martinez, G.; Gomezelvira, J. M.;
TE

Millan, J. On a novel interpretation of PVC antiplastici-

zation based on some local chain conformations. Polym.
Bull 32 (3) (1994) 353-359.
[35] Guarrotxena, N.; Martinez, G.; Millan, J. On the
EP

relationship between tacticity dependent molecular mi-

crostructure and glass transition temperature of
poly(vinyl chloride): A novel approach through model
polymers with controlled, chemically induced micro-
C

structure. Polymer 38 (8) (1997) 1857-1864.

[36] Minjagos, C.; Lopez, D. Effect of solvent on
AC

glass transition temperature in chemically modified

polyvinyl chloride (PVC). Colloid Polym Sci 272,
(1994) 159-167.
[37] Eyckens, D. J.; Champion, M. E.; Fox, B. L.;
Yoganantharajah, P.; Gibert, Y.; Welton, T.; Henderson,
L. C. Solvate Ionic Liquids as Reaction Media for Elec-
trocyclic Transformations. Eur. J. Org. Chem. (5)
(2016) 913-917.
[38] Bozic-Weber, B.; Constable, E. C.; Hostettler,
N.; Housecroft, C. E.; Schmitt, R.; Schonhofer, E. The
d(10) route to dye-sensitized solar cells: step-wise as-
sembly of zinc(II) photosensitizers on TiO2 surfaces.
Chem. Commun. 48 (46) (2012) 5727-5729.

15
 ACCEPTED MANUSCRIPT

Highlights

Phthalate Plasticizers Covalently Linked to PVC via Copper-Free

or Copper Catalyzed Azide-Alkyne Cycloadditions

PT
RI
• (2-Ethylhexyl) phthalate esters are synthesized with ester or ether alkyne linkages.

SC
• These derivatized alkyne phthalates react with a simple secondary azide model.

• Phthalates are attached to azidized PVC by thermal or Cu catalyzed cycloaddition.

U
• The rotationally free ether is a better internal plasticizer by Tg than the ester.
AN
M
D
TE
C EP
AC