Open-Resonance-Assisted Hydrogen Bonds and Competing Quasiaromaticity

Article abstract of DOI:10.1021/acs.joc.8b01331

The delocalization of electron density upon tautomerization of a proton across a conjugated bridge can alter the strength of hydrogen bonds. This effect has been dubbed resonance-assisted hydrogen bonding (RAHB) and plays a major role in the energetics of the tautomeric equilibrium. The goal of this work was to investigate the role that π-delocalization plays in the stability of RAHBs by engaging other isomerization processes. Similarly, acid-base chemistry has received little experimental attention in studies of RAHB, and we address the role that acid-base effects play in the tautomeric equilibrium. We find that π-delocalization and the disruption of adjacent aromatic rings is the dominant effect in determining the stability of a RAHB.

Full text of DOI:10.1021/acs.joc.8b01331

Subscriber access provided by READING UNIV
Article
Open Resonance Assisted Hydrogen Bonds and Competing Quasiaromaticity
Yen H. Nguyen, Bryan J. Lampkin, Amrit Venkatesh, Arkady Ellern, Aaron J Rossini, and Brett VanVeller
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01331 • Publication Date (Web): 19 Jul 2018
Downloaded from http://pubs.acs.org on July 19, 2018
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 21
The Journal of Organic Chemistry
1
2
3
4
Open Resonance Assisted Hydrogen Bonds and Competing Quasiaromaticity
5
6
7
8
Yen H. Nguyen, Bryan J. Lampkin, Amrit Venkatesh, Arkady Ellern, Aaron J. Rossini, and Brett
VanVeller*
9
Department of Chemistry, Iowa State University, Ames, Iowa 50011, United States
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ABSTRACT
The delocalization of electron density upon tautomerization of a proton across a conjugated bridge can
alter the strength of hydrogen bonds. This effect has been dubbed resonance-assisted hydrogen bonding
(RAHB) and plays a major role in the energetics of the tautomeric equilibrium. The goal of this work was
to investigate the role that π-delocalization plays in the stability of RAHBs by engaging other
isomerization processes. Similarly, acid-base chemistry has received little experimental attention in
studies of RAHB and we address the role that acid-base effects play in the tautomeric equilibrium. We
find that π-delocalization and the disruption of adjacent aromatic rings is the dominant effect in
determining the stability of a RAHB.
INTRODUCTION
The tautomeric equilibrium between enolimines (OH-form) and enaminones (NH-form, Figure 1A) plays a
critical role in biosynthesis and medicinal chemistry.1 For example, the Schiff bases of pyridoxal
phosphate (Figure 1B) are important in the enzymatic transformations of amino acids, where proton
transfer between oxygen and nitrogen is often the first step of the catalytic cycle.2-4 Additionally, several
enolimine drugs have been reported that act on the central nervous system5,6 and K+ channels.7 Similarly,
sirtinol (Fig 1B) is a deacetylase inhibitor8 that displays anticancer9-14 and antiviral15 activity. The structure
of sirtinol features a Schiff base with 2-hydroxynaphthalene, which is important for drug action.8,16
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 21
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 1. A, tautomeric equilibrium of enolimine and enaminone. B, tautomeric examples.
The balance of the equilibrium between both tautomeric forms is partially dependent on the π-
delocalization in both of the rings indicated in Figure 1A (a and q).17-22 The π-delocalization in ring q
favors the enaminone (NH-O) tautomer with a strong O•••H hydrogen bond23,24 and this stabilization is
termed a resonance-assisted hydrogen bond (RAHB).1,21,23-27 While the tautomeric equilibrium can be
affected by substituents,1,28 in general, an increase in the aromaticity of ring q leads to a loss of
aromaticity in ring a,1,16,21,29,30 and these results suggest that π-delocalization in ring a and q are coupled
to each other. This interplay was recently demonstrated to operate in the excited state as well.31 To
investigate the coupling of π-delocalization further, we sought to “open up” the RAHB to engage a new
tautomeric, quasiaromatic structure (Scheme 1). Previous studies have sought to entice the proton in
Figure 1A away from the traditional RAHB but have not been successful.16
Scheme 1. Tautomeric forms under consideration
ACS Paragon Plus Environment

Page 3 of 21
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Intriguingly, the RAHB equilibrium of Figure 1A has not received much attention in the context of
heterocycles. Most experimental studies have focused on all-carbon cycles except for some reports that
employ the pyridine or quinolone nitrogen in the role of the Schiff-base in Figure 1A.32-34 We hypothesized
that nitrogen heterocycles could suitably position Lewis basic atoms to coax the NH-O form to open up to
an unprecedented NH-N form (Scheme 1). To test our hypothesis, we elected to focus on 1 and 2
(Scheme 1 and 2) for three reasons: (i) The geometry of the RAHB in ring q’ is different for both
compounds. The 6-membered pyrazine ring in 1 presents a different hydrogen bonding geometry than the
thiadiazole ring in 2. This geometric effect might alter the stability of the RAHB in q’. (ii) The basicity of the
nitrogen atoms in each compound are different. The large difference in the pKaH values of the parent
heterocycles, pyrazine and thiadiazole (Scheme 1), may also play a role in enticing the NH-O form to
open up into the NH-N form. (iii) It has been proposed that π-delocalization within the RAHB heavily
perturbs the OH pKa, ultimately making analysis of the effect of acidity difficult35 or impossible.28 For this
reason, we sought to clarify our analysis and control for OH acidity by employing compounds with similar
“initial” pKa values at the OH group. Towards this goal, we selected quinoxaline (3) and benzothiadiazole
(4) because we measured similar OH pKa values for both compounds (Figure 2). The similar acidities of
these base heterocycles also imply similar electron-withdrawing effects in both compounds.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 21
1
2
3
4
5
Figure 2. Determination of pKa of compounds 3 and 4 by monitoring the onset of phenolate
formation.36 See SI for experimental details and data processing.
6
7
8
RESULTS AND DISCUSSION
9
The synthesis of 1 and 2 commenced with diamine 5 as the starting point for both molecules. Closure of
the pyrazine ring to form 6 was achieved via condensation with glyoxal,37 while the benzothiadiazole
variant (7) was synthesized using thionyl chloride in sulfuric acid.38 Substitution of –Cl for –OH was
performed via Pd-catalyzed cross coupling to give 3 and 4.39 Installation of the aldehyde required two
distinct conditions for each heterocycle. The Reimer–Tiemann reaction was required to convert 3 to 8,40
while the Duff reaction41 using hexamethylenetetramine (HMTA) was employed to convert 4 to 9.42 The
final Schiff bases were readily accessed upon condensation with aniline in ethanol to give 1 and 2.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 2. Synthesis of 1 and 2.
Examination of the NMR data of 1 and 2 provided insight into the dynamic tautomeric equilibrium
proposed in Scheme 1 and reveals that the unprecedented NH-N form was present in both compounds.
Various NMR solvents were used for the characterization of compounds 3–9, and assigned NMR spectra
for 1 and 2 in CDCl3 used for analysis can be found in the SI (pages S3-S4).
A. Evidence of only two forms in solution
The OH and NH-O forms cannot be distinguished spectroscopically because proton exchange is
fast on the NMR time-scale. Thus, a single peak is observed for the OH/NH-O ensemble (Figure 3, Table
1). For both 1 and 2, however, another form is observable in solution and corresponds to the NH-N form.
Other tautomeric structures of 1 and 2 were disqualified because they were deemed to be too high in
ACS Paragon Plus Environment

Page 5 of 21
The Journal of Organic Chemistry
1
2
3
4
energy to warrant consideration based on their calculated energies (Scheme 3, vide infra and Figure
5
6
S20).
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 3. NMR data for (A) 1 and (B) 2. One-dimensional 1H NMR (top) and 1H projections from the 2D
1H{15N} HMBC experiments (bottom).
B. Dominance of NH-O within the OH/NH-O ensemble
Both 1 OH/NH-O and 2 OH/NH-O exist predominantly (> 85%) in their NH-O forms, as evinced by
the following data summarized in Table 1: (i) A 3JHH splitting is observed between H7 and NH8 for both
compounds (Figure 3, Table 1, row 1 and 2), indicating that the NH-O form dominates over the OH form.
(ii) The chemical shift of C1 in both compounds (row 3) approaches a shift more similar to a carbonyl
carbon (~190 ppm) than a phenolic carbon (~160 ppm). (iii) The chemical shift of 15N8 (row 4) similarly
indicates the dominance of the NH-O form. The observed 15N chemical shifts are typical of those for
conjugated NH (ca. –200 ppm), while an imine nitrogen chemical shift typically occurs between –25 to –
90 ppm.43 Finally, Figure 4 displays the X-ray crystal structures of 1 and 2 with the position of H8
determined by dispersion-corrected plane-wave DFT calculations. Plane-wave DFT was used to take
account of the periodicity of the crystal structure and more accurately locate the hydrogen atom within the
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 21
1
2
3
4
5
6
7
8
9
crystal structure. The experimentally measured C–C, C–N and C–O bond lengths correspond to those of
the NH-O form and are consistent with the NH tautomer being the lower energy form in the crystal
state,1,44 likely due to the higher proton affinity of N versus O.29,45-48 Previously reported crystal structures
of Schiff-base RAHB compounds can show solid-state intermolecular interactions that directly contact the
RAHB and cause the OH form to be lower in energy. In contrast to these previous reports,49,50 however,
there are no clear intermolecular interactions with the RAHB of 1 and 2 evident in the crystal states
(Figure S15 and S16).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
C. Evidence for the NH-N form
Inspection of the 1H{15N} HMBC NMR spectra reveals two distinct cross-peaks that reveal the
1JNH(1H8-15N8) coupling (Figure 3). The major set of 1H NMR signals corresponds to the NH-O form and
the second, minor set of signals are assigned to the NH-N form in both 1 and 2. The ratio between the
OH/NH-O ensemble and the NH-N form was measured directly from the proton signal integration and
indicates that only 6% and 15% of 1 and 2 are found in the NH-N form, respectively (Table 1, row 5). It is
noteworthy that the NH-N form opens up the classical RAHB in ring q to form an unprecedented, new
quasiaromatic ring q’.16 The tautomeric state of the NH-N form is similarly support by the spectroscopic
evidence as for NH-O above (rows 1–4). Transfer of the proton to the nitrogen of the heterocycle (from
N8-H to N3-H) was calculated to be too high in energy to be observable (Scheme 3). However, the
1H{15N} HMBC NMR show a weak correlation between H8 and N3 at lower temperatures of 273 K,
consistent with the presence of a weak hydrogen bond (Figure S12).
ACS Paragon Plus Environment

Page 7 of 21
The Journal of Organic Chemistry
1
2
3
4
5
6
Table 1. Spectral data in support of tautomeric equilibrium and open RAHB.
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Row
1. 1H7 ppm
2. 1H8 ppm
9.64
15.24
9.0
179.3
–197.9
67.2
94
8.97
13.20
13.7
183.3
–233.8
89.5
9.05
14.19
10.7
184.0
–229.4
84.2
85
8.74
11.32
14.4
184.1
–243.3
91.2
1H7–1H8 coupling (Hz)
3. 13C1 ppm
4. 15N8 ppm
1H8–15N8 coupling (Hz)
5. 1H7 Integr. Ratio (%)
6. Tautomeric NH-O% a
6
15
65
96
7. Overall population (%)
33
61
6
4
81
15
8. NICS(1) a
9. HOMED a
10. HOMED q
11. HOMED a (from xray)
12. HOMED q (from xray)
13. HOMED q’
14. HOMED c
15. NICS(1) c
–9.74
0.924
0.849
–4.27
0.762
0.892
0.873
0.953
–2.16
0.682
–6.66
0.876
0.860
–2.66
0.714
0.884
0.795
0.926
–1.26
0.646
0.937
0.983
–9.39
–8.50
0.906
0.983
–9.54
–10.50
0.977
–13.24
–10.02
0.983
–9.35
–9.04
0.977
–13.42
–12.91
0.983
–9.37
–11.20
16. NICS(1) b
All energetic (kcal/mol, 298 K), geometric and NMR shielding calculations performed at B3LYP/6-
311+g(d,p). NICS(1), HOMED values calculated for the 6-membered ring indicated by (a). NICS(1) values
are reported as the negative isotropic shielding of a ghost atom 1.0 Å above the plane of the ring.
HOMED: 0.0–0.4, 0.4–0.8, and 0.8-1.0 signify weak, moderate, and strong delocalization respectively.
See SI for methods to calculate HOMED. All 15N chemical shifts are referenced to CH3NO2. Experimental
energy values measured by variable temperature NMR (see SI for details). aNH-O% = [1JNH/(96 Hz) x
100%].
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 21
1
2
3
4
D. Quantification of tautomeric population
The 1H NMR spectra were integrated to quantify the relative amounts of OH/NH-O and NH-N and
showed that the NH-N form represents 6% and 15% of the total molecules in solution for 1 and 2,
respectively (row 5). Based on these populations, we determined the ∆G0 difference between the OH/NH-
O ensemble and the NH-N form at 298K to be 1.62 and 1.01 kcal/mol for 1 and 2, respectively.
The relative amount of OH versus NH-O form within the OH/NH-O ensemble (the NH-O%, Table
1, row 6), can be estimated by measuring how closely the 1JNH value of NH8 corresponds to an idealized
1JNH value of 96Hz.44,51,52 Numerous studies make use of 13C and 17O chemical shifts to estimate the
%NH-O form, but there is often disagreement between the methods used to calculate the final NH-
O%.16,53-55 Indeed, recent theoretical studies suggest the NMR chemical shift of atoms within the RAHB is
not a reliable proxy for determining the equilibrium.56,57 Furthermore, the electron withdrawing nature of
the heterocycles in 1 and 2 will also perturb the chemical shifts. Therefore, chemical shift is likely an
inappropriate metric in our system. Thus, the %NH-O form within the OH/NH-O ensemble is most
accurately determined from the 1JNH coupling values that have historically been a more reliable indicator
than 3JH7–H8 coupling values.58
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 4. Single crystal X-ray diffraction structures of 1 NH-O and 2 NH-O comparing experimental and
calculated (in brackets) bond lengths. Heavy-atom bond lengths were calculated using molecular DFT
B3LYP/6-311+g(d,p). The H8 position and N8-H8 bond lengths were predicted with dispersion-
corrected plane-wave DFT calculations with heavy atom positions fixed from single X-ray diffraction.
Bond lengths for 2 NH-O are an average of two structurally independent molecules in the asymmetric
unit (s.u. are 0.004 for 1 NH-O and 0.003 Å for 2 NH-O). Anisotropic thermal ellipsoids depicted in
(Figure S17).
ACS Paragon Plus Environment

Page 9 of 21
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
The 1JNH coupling values were measured for 1 and 2 using 1H{15N} HMBC NMR on a cryoprobe
800 MHz spectrometer and 1JNH was found to be 67.2 Hz and 84.2 Hz for 1 and 2 respectively (Figure 3,
Table 1 row 4). The measured 1JNH were converted to %NH-O via the equation %NH-O = [1JNH/(96 Hz) x
100%] (row 6). The 1JNH coupling values were also measured for the NH-N form in each case. Both 1 NH-
H and 2 NH-N show nearly identical 1JNH (15N8–1H8) coupling values of 89.5 and 91.2 Hz, respectively
(row 4), which suggests that both NH-N forms exist, to the same extent, with the proton predominantly on
N8. These measured 1JNH are consistent with computational results that show proton transfer to the
nitrogen atom in the heterocycle is energetically unfavorable (Figure S20). These results indicate that the
geometry of the hydrogen bond and the basicity of the heterocyclic nitrogen (see pKaH values of the
parent heterocycles, Scheme 1) are unlikely to play a large role in the stability of the RAHB within NH-N
because the heterocyclic nitrogen atoms do not appear to interact very strongly with H8.
E. Energetic balance of tautomers
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The data from row 5 and 6 in Table 1 can be used to estimate the overall population of tautomers
in solution (row 7) by multiplying the %NH-O for each OH/NH-O ensemble (row 6) by the integration value
for 1H7 (row 5). The values of NH-O% (Table 1, row 6) further confirm that the NH-O form is the majority
form within the OH/NH-O ensemble for both 1 and 2. Interestingly, however, the 1 OH/NH-O ensemble is
closer to parity, with the 1 NH-O form slightly dominant, while the 2 OH/NH-O ensemble is almost
completely dominated by the 2 NH-O form. These results align with the smaller calculated energy
difference between 1 OH and 1 NH-O (1.28 kcal/mol) versus 2 OH and 2 NH-O (2.96 kcal/mol) at 298 K.
Similarly, using variable temperature NMR, we determined the ∆G0 at 298K to be –1.62 and –1.01
kcal/mol for 1 and 2 respectively to confirm
F. π-Delocalization and competing aromaticity
We sought to investigate the reason behind the difference in the tautomeric equilibria of OH, NH-
O and NH-N between 1 and 2. As mentioned previously, the basicity of the heterocyclic nitrogen atoms
(Scheme 1) does not appear to play a major role. Likewise, the inherent pKa of the OH groups in each
heterocycle (3 and 4, Figure 2) are so similar, we propose that the acidity—and the electron-withdrawing
capacity of the heterocycles—plays very little role in the balance of tautomers. We therefore turned to
investigate the role that aromaticity in rings a, q and q’ might play in 1 and 2 (Table 1, rows 8–13).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 21
1
2
3
4
5
6
7
8
9
Briefly, the aromaticity of a molecule can be estimated using computational chemistry to calculate
the Nucleus Independent Chemical Shift (NICS) of a dummy atom placed 1 Å above the plane aromatic
ring.59 The more negative the NICS value, the more aromatic the ring (full NICS plots from 0–4 Å can be
found in the SI, Figure S21). Alternatively, the Harmonic Oscillator Model of Electron Delocalization
(HOMED)60 is a geometry-based measure of aromaticity in which the closer the HOMED value is to 1, the
more aromatic the molecule. An older index, HOMA61 is prevalent in the literature of RAHB, and HOMA
values have also been calculated and can be found in the SI (Table S3). We elected to go with HOMED
in place of HOMA because HOMED is derived from computationally determine structural parameter, and
we sought to cancel out any potential computational errors with the computed structures for 1 and 2.
In general, for compounds 1 and 2, ring a loses aromaticity upon tautomerizing from the OH form
to the NH-O form as indicated by both NICS(1) and HOMED methods (Table 1, rows 8 and 9). The
aromaticity in ring a for the OH forms, however, is greater for 1 than for 2. Thus, there is a smaller
sacrifice of aromaticity in ring a for 2 upon tautomerization to the NH-O form, which explains why 2 exists
in the NH-O form to a greater extent than 1. Likewise, a small increase in the aromaticity of quasi-
aromatic ring q is observed for both compounds upon tautomerization to NH-O (row 10). This observation
aligns with previous reports that show ring q always displays significantly less change in its index of
aromaticity relative to the sacrifice of aromaticity in ring a to form the RAHB.16 The overall trend of this
data is mirrored in the HOMED indices calculated from the X-ray crystal structures of 1 and 2 (rows 11
and 12).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
For the NH-N forms, the quasiaromatic ring q’ display high aromatic character according to
HOMED indices (row 13), while ring a in each case loses still more aromatic character (row 9) relative to
the NH-O forms. Again, we attribute the lower aromaticity in ring a of 2 as the reason that 2 displays more
of the NH-N form in solution compared to 1.
ACS Paragon Plus Environment

Page 11 of 21
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3. Proton transfer to the heterocyclic ring nitrogen disrupts the aromaticity in both rings of the
heterocycle. Energy differences calculated using DFT B3LYP/6-311+g(d,p).
These results suggest that acid-base effects play very little role in determining the equilibrium of 1
and 2, and the equilibrium is chiefly governed by aromaticity. We further propose that aromaticity
considerations account for why proton transfer from N8 to N3 does not occur (described in section C
above) (Scheme 3). The energy difference between 1 NH-N to 10 and 2 NH-N to 11 is too large to have
an appreciable concentration at equilibrium. Tautomerization to form either 10 or 11 disrupts the
aromaticity of both rings in the heterocycle because of π-delocalization to form the new q’ N8-HN3
quasiaromatic ring. We propose that this aromatic disruption is the main factor responsible for the large
energy difference.
Finally, rings b and c appear to be largely spectators in this isomerization process (Table 1, rows
14-16). HOMED values for ring c (row 14) indicate no change in aromaticity during tautomerization. The
NICS(1) values (row 15), however, show a slight decrease in aromaticity of ring c upon tautomerization to
the NH-O and NH-N forms which is likely due to changes in conjugation along the RAHB which alters
conjugation effects and electron density within ring c. HOMED values were not calculated for ring b
because N–S bonds have not been parameterized for analysis.60 Alternatively, NICS(1) values were
calculated for compounds 1 and 2 (row 16). In general, ring b in both 1 and 2 experiences very little
change in aromaticity across the different tautomers. Comparison between ring b of 1 and 2 is not
appropriate because of the different ring sizes (6-membered vs 5-membered) in 1 and 2. 5-Membered
rings typically appear 'more aromatic' than 6-member rings because the NICS measurement quantifies
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 21
1
2
3
4
5
6
the magnetic field at the center of the ring. Thus, the field is enhanced as the π-bonds move closer to the
point where NICS is being measured.
7
8
9
CONCLUSION
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Collectively, these results indicate that resonance-assisted hydrogen bonds (RAHB) can be
opened up provided there is a suitable Lewis base to stabilize the proton. This effect has not been
observed before in the literature of RAHB, and we provide the first characterization of such an effect to
open a RAHB to form quasi-aromatic ring q’. We also sought to investigate the effect that acid-base
interactions might have on the RAHB and the equilibrium in Figure 1. We selected quinoxaline (3) and
benzothiadiazole (4) as the base heterocycles for this analysis because our measurements revealed
them to have very similar pKa values for their hydroxyl groups. These similar acidities, allowed us to
isolate the aromaticity in ring a as the chief factor in determining the balance of tautomers in the OH/NH-
O equilibrium ensemble. Similarly, the difference in basicity of the heterocyclic nitrogen atoms in the NH-
N tautomer did not appear to influence the position of the proton in the RAHB (based on 1JN8–H8 coupling
values in NH-N. These findings supports the primacy of aromaticity and π-delocalization in determining
the tautomeric position in RAHB.
EXPERIMENTAL SECTION
Materials. Silica gel (40 µm) was purchased from Grace Davison. All solvents used for photophysical
experiments were reagent grade. 4-chlorobenzene-1, 2-diamine (1) was purchased from Oakwood
Chemicals, Palladium catalyst from Strem Chemicals, Hexamethylenetetramine from Alfa Aesar. All other
reagents were purchased from Sigma Aldrich and used without further purification.
General Method. NMR Spectroscopy: 1H and 13C NMR spectra for all compounds were acquired in
deuterated solvents (as indicated) on a Bruker Spectrometer at the field strengths reported in the text.
The chemical shift data are reported in units of δ (ppm) relative to residual solvent. 1D 1H NMR and 1H-
13C HMBC NMR spectra were obtained using a 600 MHz Bruker Avance III spectrometer. Quantitative 1D
1H NMR spectra were obtained at different temperatures for the thermodynamic analysis using long
recycle delays of 100 s (> 5 × T1) between subsequent scans. 1H-15N HMBC NMR spectra were recorded
using a 700 MHz Bruker Avance II NMR spectrometer. IR Spectroscopy: Solutions of 1 and 2 in CCl4
ACS Paragon Plus Environment

Page 13 of 21
The Journal of Organic Chemistry
1
2
3
4
5
6
were dropped onto KBr plates before collection of the spectrum on a Bruker Vertex 80 FTIR
spectrometer.
7
8
9
General Computational. All molecules considered were optimized at the nonlocal three-parameter
hybrid B3LYP level of theory62,63 under the 6-311+g(d,p) basis set. Vibrational analysis of each structure
verified the existence of a minima due to the absence of imaginary frequencies. All calculations were
carried out with the Gaussian 09 package.64 Additionally, the hybrid CAM-B3LYP65 and M06-2X66
functionals were also for their ability to model charge transfer reactions and weak non-covalent
interactions, respectively (Table S4). However, recent literature precedent has utilized the B3LYP
functional to model proton transfer reactions and isomerizations.67-69
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
HOMED values were obtained by using equation 1 where j indicates the bond type.
∑
ꢈ
ꢉꢊꢋꢌꢍꢎꢏ ꢇ ꢊꢐꢎꢏꢑꢒ
ꢓ
ꢀꢁꢂꢃꢄ ꢅ ꢆ ꢇ
Ropt and α values used were from Raczyńska et. al. initial report of HOMED:60 CC(Ropt = 1.394, α2i =
88.09), CN(1.334, 91.60), CO(1.281, 75.00).
Plane-wave DFT calculations were performed on compounds 1 and 2 using CASTEP.70 The X-ray crystal
structures were used to fix the heavy atom positions and the hydrogen atom positions were optimized. All
calculations used the Perdew-Burke-Ernzerhof (PBE) functional71 with the Tkatchenko-Scheffler (TS)
dispersion correction scheme72 and ultra-soft pseudopotentials generated on-the-fly. The wavefunctions
were expanded using a plane-wave basis set with a kinetic energy cut-off of 630 eV. A Monkhorst-Pack
grid with a k-point spacing of 0.07 Å-1 was used to calculate the integrals over the Brillouin zone.
Synthesis of 6-chloroquinoxaline (6). The diamine 5 (428 mg, 3.00 mmol) was added to a solution of
glyoxal in water and stirred at RT for 1h. Upon completion (determined by TLC), the reaction was
extracted with DCM, dried over MgSO4 and concentrated in vacuo. 1H NMR of the crude product matched
previously reported literature.37 1H NMR (CDCl3, 600Hz): δ 8.83 (d, J = 6 Hz, 2H), δ 8.09 (s, 1H), δ 8.03
(d, J = 9 Hz, 1H), δ 7.70 (d, J = 8.4 Hz, 1H).
Synthesis of quinoxalin-6-ol (3). Compound 6 (164 mg, 1.0 mmol), K2CO3 (414 mg, 3.0 mmol) and
precatalyst Pd-t-BuXphos (40 mg, 5.0 mol %) (see SI for structure) were added together in a vial, then
vacuumed and back-filled with nitrogen three times. Next, 5 mL of degassed DMF/water (5:1 v/v) was
added. The reaction mixture was stirred at 115 oC for 4 h. Upon completion, the reaction was poured into
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 21
1
2
3
4
5
6
7
8
9
1M HCl and extracted with diethyl ether three times. The combined organic fractions were dried over
MgSO4 and concentrated in vacuo. The crude residue was triturated with hexane and DCM to give 3
(87.6 mg, 60% yield). 1H NMR of the product matched previously reported literature.73 1H NMR (DMSO,
600Hz): δ 10.56 (s, OH, 1H), δ 8.77 (d, J = 2.4Hz, 1H), δ 8.67 (d, J = 2.4 Hz, 1H), δ 7.90 (d, J = 9 Hz,
1H), δ 7.42 (dd, J = 9 Hz, 2.7 Hz, 1H), δ 7.24 (d, J = 2.7 Hz, 1H).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Synthesis of (Z)-5-((phenylamino)methylene)quinoxalin-6(5H)-one (1). Compound 3 (1.0 mmol, 146
mg) and NaOH (4.0 mmol, 160 mg) were dissolved in 2.0 mL of water by heating to 100 oC for 30 min.
Then 1.5 mL chloroform was added with vigorous stirring. More NaOH was added to keep the pH of the
reaction at 10 (determined with pH paper). Upon completion, the reaction was acidified to pH 6, and the
solid was collected by filtration. The crude product was condensed with excess aniline (1.0 mL) in 5.0 mL
DCM at 45 oC, in a seal tube for 1h and monitored by TLC. The reaction was quenched with 1M HCl. The
organic layer was separated, concentrated under vacuum and purified by silica gel column
chromatoghraphy (1:5 EtOAc:Hex) to obtain the final product 1 (99 mg, 40%). 1H NMR (DMSO, 600 Hz):
δ 9.67 (s, 1H), δ 8.73 (s, 1H), δ 8.63 (s, 1H), δ 7.92 (d, J = 9.68 Hz, 1H), δ 7.58 (d, J = 7.4 Hz, 2H), δ 7.50
(t, J =7.4 Hz, 2H), δ 7.34 (t, J = 7.4 Hz, 1H), δ 7.15 (d, J = 9.68 Hz, 1H). 13C NMR (DMSO, 150 Hz): δ
176.3, 153.5, 144.5, 141.6, 140.9, 137.1, 136.9, 129.9, 129.3, 127.0, 119.7, 108.0. HRMS (ESI, TOF)
m/z: [M +H]+ Calcd for C15H11N3O 250.0975, found 250.0975.
Synthesis of 5-chlorobenzo[c][1,2,5]thiadiazole (7). Based on a previously reported procedure,38 4-
chlorobenzene-1,2-diamine (1.43 g, 10 mmol) was added to a flame dried round bottom flask and placed
under nitrogen. SOCl2 (8.2 g, 5.0 mL, 68 mmol) and 0.220 mL of concentrated H2SO4 (405 mg, 4.1 mmol)
were subsequently added. The reaction mixture was refluxed for 6 h and cooled to RT. The solution was
diluted with water and extracted with EtOAc. The EtOAc phase was repeatedly washed with water until
the aqueous phase was no longer acidic by pH paper. The organic phase was dried over MgSO4 and
concentrated under vacuum. The crude mixture was purified by silica gel flash column chromatography
(5:1, Hexanes: EtOAc, Rf = 0.7) to afford the product 7 as a reddish brown solid (1.2 g, 70%). 1H NMR
(CDCl3, 400 MHz) δ 7.85 (d, J = 4 Hz, 1H), δ 7.77 (d, J = 12 Hz, 1H), δ 7.38 (dd, J = 4 Hz, 6 Hz, 1H).
Spectra of product match those previously reported.38
ACS Paragon Plus Environment

Page 15 of 21
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Synthesis of benzo[c][1,2,5]thiadiazol-5-ol (4). Compound 7 (17.0 mg, 0.10 mmol), KOH (17.0 mg,
0.30 mmol) and 3.96 mg (5% mmol) of Pd-t-BuXPhos precatalyst (see SI for structure) were added to a
flame dried round bottom flask. The reaction flask was evacuated and back filled with nitrogen three times
before 36 µL of degassed water:DMF (1:9 v:v) was added. The reaction was stirred for 18h at 80 oC.
Upon cooling to RT, the reaction was diluted with water, acidified with 1M HCl and extracted with EtOAc
three times. The combined organic fractions were dried over MgSO4 and concentrated under vacuum.
The residue was purified by silica gel flash column chromatography (start with 5:1 and gradient to 1:1,
Hexanes:EtOAc, Rf = 0.2) to afford a light yellow solid (10.6 mg, 70%). 1H NMR ((CD3)2CO, 600 Hz), δ
7.88 (d, J = 9.6 Hz, 1H), δ 7.37 (dd, J = 2.40 Hz, 9.6 Hz, 1H), δ 7.22 (d, J = 2.4 Hz, 1H). Spectra of
product match those previously reported.39
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Synthesis of 5-hydroxybenzo[c][1,2,5]thiadiazole-4-carbaldehyde (9). Based on a previously reported
procedure,42 4 (76 mg, 0.50 mmol) and hexamethylenetetramine (HMTA) (70 mg, 0.50 mmol) were
dissolved in 1.0 mL of TFA in a round bottom flask at RT. After the consumption of starting material
(tracked by TLC), the reaction was heated to 70 oC for 48 h. Upon cooling to RT, the reaction was
quenched with water and the mixture was extracted with ethyl acetate. The EtOAc portion was dried over
MgSO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (1:1,
Hexanes:EtOAc, Rf = 0.35) to afford a crude orange yellow product that was used without further
purification (44 mg, 49.0 %). 1H NMR (CDCl3, 600 MHz) δ 13.0 (br s, OH, 1H), δ 10.7 (s, CHO, 1H), δ
8.11 (d, J = 9.6 Hz, 1H), δ 7.33 (d, J = 9.6 Hz, 1H). 13C NMR (CDCl3, 150 MHz) δ 193.7, 167.4, 154.2,
150.3, 130.0, 124.8, 108.82. HRMS (ESI, TOF) m/z: [M - H]- Calcd for C7H4N2O2S 178.9921, found [M-H]
178.9897.
Synthesis of (Z)-4-((phenylamino) methylene)benzo[c][1,2,5]thiadiazol-5(4H)-one (2). Compound 9
(108 mg, 0.60 mmol) was dissolve in EtOH (3.0 mL, 0.50 M in 9). Aniline (54 mg, 0.60 mmol) was added,
and the reaction was warmed to 40 oC and tracked by TLC until completion. The reaction was poured into
water and extracted with ethyl acetate. The EtOAc portion was dried over MgSO4 and purified by silica gel
flash chromatography (5:1, Hexanes:EtOAc, Rf = 0.45) to give a quantitative yield of 2 (153 mg, 99%). 1H
NMR (CDCl3, 400 Hz): δ 14.2 (d, J = 10.4 Hz, 1H, H8), δ 8.90 (d, J = 11.2 Hz, 1H, H7), δ 7.63 (d, J = 9
Hz, 1H), δ 7.36 (m, 2H), δ 7.33 (m, 2H), δ 7.2 (t, J = 7.4 Hz, 1H). 13C NMR (CDCl3,100 Hz): δ 183.1,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 21
1
2
3
4
156.4, 149.4, 149.0, 138.5, 131.9, 129.9, 129.3, 126.6, 118.3, 104.7. HRMS (ESI, TOF) m/z: [M +H]+
5
6
Calcd for C13H9N3OS 256.0539, found (M+H) 256.0568.
7
ASSOCIATED CONTENT
8
9
The Supporting Information is available free of charge on the ACS Publications website at DOI:
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Structures of catalysts discussed in the main text, DFT calculations, computational analyses, pKa studies
and NMR spectra. X-ray crystal structures have been deposited in the Cambridge Crystallographic Data
Centre (1844550 and 1844551).
AUTHOR INFORMATION
Corresponding Author
*Email: bvv@iastate.edu
ORCID
Brett VanVeller: 0000-0002-3792-0308
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are grateful for support of this work by Iowa State University of Science and Technology and a Pfizer
Global ASPIRE Award (WI216840).
REFERENCES
ꢀ
ꢁꢂꢃꢀ
ꢍꢢꢟꢓꢣꢓꢤꢡꢓꢅꢀꢓꢜꢀꢄꢝꢣꢅꢠꢓꢒꢜꢀꢠꢒꢀꢥꢓꢦꢍꢣꢝꢆꢠꢡꢒꢜꢀꢏꢝꢣꢒꢆꢅꢣꢓꢇꢅꢠꢓꢒꢜꢎꢀ/ꢀꢁꢂꢃ wꢁꢄꢃꢀꢀꢁꢁꢂꢌꢀ ꢅꢆꢌꢀꢧꢨꢩꢂꢎꢀ
ꢁꢪꢃꢀ ꢥꢫꢓꢣꢣꢓꢬꢊꢌꢀꢄꢎꢀꢭꢫꢝꢗꢓꢊꢠꢡꢈꢀꢅꢜꢮꢀꢏꢓꢯꢝꢡꢊꢓꢠꢈꢀꢒꢰꢀꢥꢈꢡꢓꢮꢒꢱꢅꢣꢦꢨꢲꢦꢥꢫꢒꢊꢬꢫꢅꢠꢝꢀꢏꢝꢬꢝꢜꢮꢝꢜꢠꢀ
ꢍꢜꢇꢈꢗꢝꢊꢎꢀ.ꢇꢈꢉꢀꢇꢂ .ꢇꢈꢊꢀꢋꢌ !ꢉꢍꢎꢃꢀꢀꢁꢃꢂꢌꢀ ꢏꢆꢐꢌꢀꢂꢂꢩꢳꢎꢀ
ꢁꢧꢃꢀ ꢴꢫꢅꢡꢓꢰꢌꢀꢴꢎꢐꢀꢏꢝꢜꢓꢊꢒꢯꢌꢀꢛꢎꢀꢴꢎꢐꢀꢞꢒꢜꢝꢈꢌꢀꢵꢎꢀꢏꢎꢐꢀꢶꢓꢗꢤꢅꢆꢫꢌꢀꢷꢎꢀꢷꢎꢀꢸꢗꢡꢀꢴꢠꢟꢮꢓꢝꢊꢀꢒꢰꢀꢴꢒꢣꢯꢝꢜꢠꢦ
ꢄꢅꢆꢇꢈꢉꢊꢋꢅꢌꢀꢍꢎꢀꢏꢎꢐꢀꢑꢒꢊꢓꢉꢊꢋꢅꢌꢀꢔꢎꢐꢀꢕꢖꢗꢓꢅꢘꢒꢙꢊꢋꢓꢌꢀꢚꢎꢐꢀꢛꢅꢙꢓꢜꢝꢆꢋꢓꢌꢀꢄꢎꢀꢞꢅꢟꢠꢒꢗꢝꢡꢓꢆꢀ
ꢀ
ꢀ
ꢹꢊꢊꢓꢊꢠꢝꢮꢀꢥꢡꢒꢠꢒꢜꢀꢞꢡꢅꢜꢊꢰꢝꢡꢀꢓꢜꢀꢅꢀꢚꢓꢒꢣꢒꢺꢓꢆꢅꢣꢣꢈꢀꢄꢝꢣꢝꢯꢅꢜꢠꢀꢴꢆꢫꢓꢰꢰꢀꢚꢅꢊꢝꢻꢀꢞꢒꢙꢅꢡꢮꢀꢅꢀꢏꢓꢊꢠꢓꢜꢆꢠꢓꢒꢜꢀꢒꢰꢀ
ꢛꢝꢒꢗꢝꢠꢡꢓꢆꢀꢅꢜꢮꢀꢍꢢꢟꢓꢣꢓꢤꢡꢓꢟꢗꢀꢷꢦꢚꢒꢜꢮꢀꢼꢊꢒꢠꢒꢬꢝꢀꢍꢰꢰꢝꢆꢠꢊꢎꢀWꢃ !ꢂꢃ /ꢀꢁꢂꢃ {ꢈꢉꢃꢀꢀꢁꢁꢄꢌꢀ ꢑꢏꢌꢀꢧꢧꢳꢨꢎꢀ
ꢀ
ꢀ
ꢁꢽꢃꢀ
ꢁꢨꢃꢀ
ꢭꢫꢡꢓꢊꢠꢝꢜꢌꢀꢥꢎꢐꢀꢵꢝꢠꢇꢣꢝꢡꢌꢀꢥꢎꢀꢍꢎꢐꢀꢍꢮꢊꢀÇꢒꢎꢓꢌꢎꢂꢇꢓꢎꢌꢁꢌꢐꢀꢔꢓꢣꢝꢈꢻꢀꢸꢝꢙꢀꢾꢒꢡꢋꢌꢀꢪꢿꢿꢨꢎꢀ
ꢑꢅꢬꢣꢅꢜꢌꢀꣀꢎꢀꢥꢎꢐꢀꢄꢅꢓꢇꢒꢜꢌꢀꢚꢎꢀꢵꢎꢐꢀꢏꢝꢊꢅꢡꢗꢝꢜꢓꢝꢜꢌꢀꢵꢎꢐꢀꣁꢝꢣꢠꢇꢌꢀꢥꢎꢐꢀꢷꢝꢅꢮꢣꢝꢈꢌꢀꢥꢎꢀꢵꢎꢐꢀꢔꢒꢡꢗꢊꢌꢀ
ꢥꢎꢐꢀꢶꢣꢒꢈꢮꢌꢀꢑꢎꢀꢛꢎꢐꢀꢚꢅꢡꢠꢫꢒꢣꢓꢜꢓꢌꢀꢛꢎꢀꢸꢝꢙꢀꢹꢜꢠꢓꢆꢒꢜꢯꢟꢣꢊꢅꢜꢠꢊꢻꢀꢴꢆꢫꢓꢰꢰꢀꢚꢅꢊꢝꢊꢀꢕꢰꢀꢎꢛꢅꢗꢗꢅꢎꢦꢹꢗꢓꢜꢒꢤꢟꢠꢈꢡꢓꢆꢀꢹꢆꢓꢮꢀ
ꢹꢜꢮꢀꢎꢛꢅꢗꢗꢅꢎꢦꢹꢗꢓꢜꢒꢤꢟꢠꢈꢡꢅꢗꢓꢮꢝꢎꢀWꢃ aꢁꢔꢃ /ꢀꢁꢂꢃꢀꢃꢅꢆꢁꢌꢀꢑ ꢌꢀꢳꢿꢪꢎꢀ
ꢀ
ꢁꢩꢃꢀ
ꢑꢡꢅꢟꢊꢝꢌꢀꢵꢎꢐꢀꢄꢒꢟꢣꢝꢅꢟꢌꢀꢹꢎꢐꢀꢴꢠꢅꢡꢋꢌꢀꢷꢎꢐꢀꢶꢟꢺꢝꢡꢌꢀꢥꢎꢐꢀꢶꢓꢬꢬꢌꢀꢄꢎꢐꢀꢛꢅꢡꢤꢅꢡꢺꢌꢀꢵꢎꢐꢀꢴꢆꢫꢙꢅꢡꢠꢌꢀꣀꢎꢀꢭꢎꢐꢀ
ꢴꢆꢫꢟꢜꢅꢆꢋꢌꢀꢔꢎꢀꢴꢈꢜꢠꢫꢝꢊꢓꢊꢌꢀꣂꢦꢄꢅꢈꢀꢭꢡꢈꢊꢠꢅꢣꢣꢒꢺꢡꢅꢬꢫꢈꢌꢀꢅꢜꢮꢀꢥꢫꢅꢡꢗꢅꢆꢒꢋꢓꢜꢝꢠꢓꢆꢊꢀꢒꢰꢀꢸꢒꢯꢝꢣꢀꢹꢇꢒꢗꢝꢠꢫꢓꢜꢝꢀ
ꢥꢡꢒꢮꢡꢟꢺꢊꢀꢒꢰꢀꢁꢄꢃꢦꢎꢹꢣꢬꢫꢅꢎꢦꢵꢝꢠꢫꢈꢣꢫꢓꢊꢠꢅꢗꢓꢜꢝꢻꢀꢷꢓꢺꢫꢣꢈꢀꢥꢒꢠꢝꢜꢠꢀꢅꢜꢮꢀꢴꢝꢣꢝꢆꢠꢓꢯꢝꢀꢷꢓꢊꢠꢅꢗꢓꢜꢝꢀꢷꢧꢀꢄꢝꢆꢝꢬꢠꢒꢡꢀ
ꢹꢺꢒꢜꢓꢊꢠꢊꢎꢀWꢃ aꢁꢔꢃ /ꢀꢁꢂꢃꢀꢃꢅꢅꢂꢌꢀ ꢏꢌꢀꢽꢿꢳꢿꢎꢀ
ACS Paragon Plus Environment

Page 17 of 21
The Journal of Organic Chemistry
1
2
3
4
5
6
ꢀ
ꢁꢳꢃꢀ
ꢵꢅꢝꢋꢅꢙꢅꢌꢀꢞꢎꢐꢀꢾꢅꢗꢅꢗꢒꢠꢒꢌꢀꢴꢎꢐꢀꢼꢺꢅꢠꢅꢌꢀꢾꢎꢐꢀꢼꢋꢝꢮꢅꢌꢀꢴꢎꢐꢀꢔꢅꢠꢅꢜꢅꢤꢝꢌꢀꢞꢎꢐꢀꢴꢫꢓꢡꢅꢓꢊꢫꢓꢌꢀꢵꢎꢀ
ꢴꢈꢜꢠꢫꢝꢊꢓꢊꢀꢅꢜꢮꢀꢚꢓꢒꢣꢒꢺꢓꢆꢅꢣꢀꢹꢆꢠꢓꢯꢓꢠꢈꢀꢒꢰꢀꢸꢒꢯꢝꢣꢀꢪꢦꢁꢹꢣꢬꢫꢅꢦꢹꢣꢋꢒꢱꢈꢓꢗꢓꢜꢒꢃꢀꢚꢝꢜꢇꢈꢣꢬꢈꢡꢓꢮꢓꢜꢝꢀꢏꢝꢡꢓꢯꢅꢠꢓꢯꢝꢊꢀꢅꢊꢀ
ꢑꣃꢀꢭꢫꢅꢜꢜꢝꢣꢀꢕꢬꢝꢜꢝꢡꢊꢎꢀ/ꢀꢁꢂꢃ tꢀꢎꢒꢂꢃ ."##ꢃ $Çꢈ%ꢋꢈ&ꢀꢃꢅꢅꢇꢌꢀꢐꢆꢌꢀꢂ꣄꣄ꢽꢎꢀ
7
ꢀ
ꢁꣅꢃꢀ
ꢛꢡꢒꢇꢓꢜꢺꢝꢡꢌꢀꢭꢎꢀꢵꢎꢐꢀꢭꢫꢅꢒꢌꢀꢍꢎꢀꢏꢎꢐꢀꢚꢣꢅꢆꢋꢙꢝꢣꢣꢌꢀꢷꢎꢀꢍꢎꢐꢀꢵꢒꢅꢇꢝꢮꢌꢀꢏꢎꢐꢀꢴꢆꢫꢡꢝꢓꢤꢝꢡꢌꢀꢴꢎꢀꢶꢎꢀ
8
9
ꢼꢮꢝꢜꢠꢓꢰꢓꢆꢅꢠꢓꢒꢜꢀꢒꢰꢀꢅꢀꢭꢣꢅꢊꢊꢀꢒꢰꢀꢴꢗꢅꢣꢣꢀꢵꢒꢣꢝꢆꢟꢣꢝꢀꢼꢜꢫꢓꢤꢓꢠꢒꢡꢊꢀꢒꢰꢀꢠꢫꢝꢀꢴꢓꢡꢠꢟꢓꢜꢀꣁꢅꢗꢓꢣꢈꢀꢒꢰꢀꢸꢅꢮꢦꢏꢝꢬꢝꢜꢮꢝꢜꢠꢀ
ꢏꢝꢅꢆꢝꢠꢈꢣꢅꢊꢝꢊꢀꢤꢈꢀꢥꢫꢝꢜꢒꢠꢈꢬꢓꢆꢀꢴꢆꢡꢝꢝꢜꢓꢜꢺꢎꢀW .ꢇꢈ# /ꢀꢁꢂꢀꢀꢁꢁꢃꢌꢀꢑ'(ꢌꢀꢧꣅꣅꢧꢳꢎꢀ
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ꢀ
ꢁ꣄ꢃꢀ
ꢀꢁꢃꢇꢌꢀ(ꢌꢀ꣄ꢽꢨꢎꢀ
ꢁꢂꢿꢃꢀ ꢕꢠꢅꢌꢀꢷꢎꢐꢀꢞꢒꢋꢟꢜꢅꢺꢅꢌꢀꢍꢎꢐꢀꢭꢫꢅꢜꢺꢌꢀꢑꢎꢐꢀꢷꢓꢋꢅꢊꢅꢌꢀꢵꢎꢐꢀꢼꢓ꣆ꢓꢗꢅꢌꢀꢑꢎꢐꢀꢍꢠꢒꢌꢀꢵꢎꢐꢀꢑꢒꢇꢅꢋꢓꢌꢀꢑꢎꢐꢀ
ꢷꢟꢌꢀꣀꢎꢐꢀꣀꢓꢜꢺꢌꢀꢷꢎꢐꢀꢶꢓꢜꢌꢀꢷꢎꢀꢴꢓꢡꢠꢟꢓꢜꢀꢼꢜꢫꢓꢤꢓꢠꢒꢡꢊꢀꢅꢊꢀꢹꢜꢠꢓꢆꢅꢜꢆꢝꢡꢀꢹꢺꢝꢜꢠꢊꢎꢀC"ꢍ"ꢒꢁ aꢁꢔ /ꢀꢁꢂꢀ
ꢀ
ꢹꢋꢓꢊꢫꢓꢠꢅꢌꢀꢵꢎꢐꢀꢕꢟꢆꢫꢓꢌꢀꢾꢎꢐꢀꢑꢅꢜꢝꢋꢓꢌꢀꢵꢎꢀꢴꢓꢡꢠꢂꢀꢼꢜꢫꢓꢤꢓꢠꢒꢡꢌꢀꢴꢓꢡꢠꢓꢜꢒꢣꢌꢀꢼꢜꢮꢟꢆꢝꢊꢀꢴꢝꢜꢝꢊꢆꢝꢜꢆꢝꢦꢶꢓꢋꢝꢀꢛꢡꢒꢙꢠꢫꢀ
ꢹꢡꢡꢝꢊꢠꢀꢙꢓꢠꢫꢀꢹꢠꢠꢝꢜꢟꢅꢠꢝꢮꢀꢄꢅꢊꢦꢵꢅꢬꢋꢀꢴꢓꢺꢜꢅꢣꢓꢜꢺꢀꢓꢜꢀꢷꢟꢗꢅꢜꢀꢭꢅꢜꢆꢝꢡꢀꢭꢝꢣꢣꢊꢎꢀhꢓꢉꢈ+ꢁꢓꢁꢀꢀꢁꢁꢄꢌꢀꢑꢆꢌꢀꢂꢳꢩꢎꢀ
ꢀ
ꣁꢟꢆꢫꢠꢝꢡꢌꢀꢵꢎꢀꣀꢎꢐꢀꢷꢊꢓꢅꢒꢌꢀꢭꢎꢀꢏꢎꢐꢀꢶꢅꢗꢌꢀꢍꢎꢀꢔꢎꢀꢴꢓꢡꢠꢀꢼꢜꢫꢓꢤꢓꢠꢒꢡꢊꢀꢼꢜꢮꢟꢆꢝꢀꢭꢝꢣꢣꢀꢏꢝꢅꢠꢫꢀꢅꢜꢮꢀꢥꢨꢧꢀꢹꢆꢝꢠꢈꢣꢅꢠꢓꢒꢜꢀ
ꢠꢫꢡꢒꢟꢺꢫꢀꢞꢅꢡꢺꢝꢠꢓꢜꢺꢀꢚꢒꢠꢫꢀꢴꢓꢡꢠꢂꢀꢅꢜꢮꢀꢴꢓꢡꢠꢪꢎꢀaꢈ# /ꢎꢓꢉꢁꢒ Çꢀꢁꢒꢃꢀꢀꢁꢃꢁꢌꢀ,ꢌꢀꣅꢽꢽꢎꢀ
ꢀ
ꢼꢠꢒꢌꢀꢵꢎꢀꢹꢀꢄꢒꢣꢝꢀꢰꢒꢡꢀꢴꢓꢡꢠꢂꢀꢓꢜꢀꢭꢝꢣꢣꢀꢛꢡꢒꢙꢠꢫꢀꢅꢜꢮꢀꢭꢫꢝꢗꢒꢡꢝꢊꢓꢊꢠꢅꢜꢆꢝꢀꢓꢜꢀꢥꢡꢒꢊꢠꢅꢠꢝꢀꢭꢅꢜꢆꢝꢡꢀꢥꢆꢧꢀꢅꢜꢮꢀꢏꢟꢂꢽꢨꢀ
ꢭꢝꢣꢣꢊꢎꢀ.ꢇꢈꢉꢀꢁꢂ .ꢇꢈꢊꢀꢋꢌ wꢁꢌ /ꢈꢂꢂ"ꢓꢀꢀꢁꢁꢆꢌꢀ ' ꢌꢀꢽꢪꢧꢎꢀ
ꢀ
ꢍꢰꢰꢝꢆꢠꢀꢒꢰꢀꢭꢒꢗꢤꢓꢜꢝꢮꢀꢞꢡꢝꢅꢠꢗꢝꢜꢠꢀꢙꢓꢠꢫꢀꢭꢓꢊꢬꢣꢅꢠꢓꢜꢀꢅꢜꢮꢀꢷꢓꢊꢠꢒꢜꢝꢀꢏꢝꢅꢆꢝꢠꢈꢣꢅꢊꢝꢀꢼꢜꢫꢓꢤꢓꢠꢒꢡꢊꢀꢒꢜꢀꢷꢝꢣꢅꢀꢭꢝꢣꢣꢊꢎꢀW
Dꢋꢓꢁꢉꢈ# hꢓꢉꢈ#ꢃꢀꢀꢁꢃꢁꢌꢀꢑ ꢌꢀꢪꢩꢪꢎꢀ
ꢀ
ꢼꢜꢫꢓꢤꢓꢠꢓꢒꢜꢀꢒꢰꢀꢴꢓꢡꢠꢂꢀꢤꢈꢀꢅꢀꢴꢗꢅꢣꢣꢀꢵꢒꢣꢝꢆꢟꢣꢝꢀꢼꢜꢮꢟꢆꢝꢊꢀꢹꢬꢒꢬꢠꢒꢊꢓꢊꢀꢓꢜꢀꢚꢡꢝꢅꢊꢠꢀꢭꢅꢜꢆꢝꢡꢀꢭꢝꢣꢣꢊꢎꢀ.ꢇꢈꢉꢀꢁꢂ
.ꢇꢈꢊꢀꢋꢌ wꢁꢌ /ꢈꢂꢂ"ꢓꢃꢀꢀꢁꢃꢁꢌꢀꢐꢅ ꢌꢀꢂꢧꢎꢀ
ꢀ
ꢁꢂꢂꢃꢀ ꢥꢝꢆꢋꢌꢀꢚꢎꢐꢀꢭꢫꢝꢜꢌꢀꢭꢎꢀꢾꢎꢐꢀꢷꢒꢌꢀꢑꢎꢀꢑꢎꢐꢀꢏꢓꢀꣁꢡꢟꢊꢆꢓꢅꢌꢀꢥꢎꢐꢀꢵꢈꢅꢠꢠꢌꢀꢴꢎꢀꢴꢎꢐꢀꢭꢒꢒꢗꢤꢝꢊꢌꢀꢄꢎꢀꢭꢎꢐꢀ
ꢁꢂꢪꢃꢀ ꢑꢒ꣆ꢓꢗꢅꢌꢀꢑꢎꢐꢀꢕꢫꢫꢅꢊꢫꢓꢌꢀꢄꢎꢐꢀꣁꢟ꣆ꢓꢠꢅꢌꢀꢾꢎꢐꢀꢷꢅꢗꢅꢮꢅꢌꢀꢸꢎꢐꢀꢹꢋꢅꢒꢌꢀꢾꢎꢐꢀꢸꢒꢇꢅꢙꢅꢌꢀꢾꢎꢐꢀꢏꢝꢺꢟꢆꢫꢓꢌꢀꢞꢎꢐꢀ
ꢁꢂꢧꢃꢀ ꣀꢓꢜꢌꢀꢑꢎꢀꢶꢎꢐꢀꢥꢅꢡꢋꢌꢀꣀꢎꢀꢾꢎꢐꢀꢸꢒꢫꢌꢀꢍꢎꢀꣀꢎꢐꢀꢷꢒꢝꢌꢀꢑꢎꢀꢶꢎꢐꢀꢶꢝꢝꢌꢀꣀꢎꢀꢷꢎꢐꢀꢑꢓꢗꢌꢀꣀꢎꢀꢷꢎꢐꢀꢸꢅꢗꢌꢀꣀꢎꢀꢷꢎꢀꢞꢫꢝꢀ
ꢁꢂꢽꢃꢀ ꢑꢅꢣꢣꢝꢌꢀꢹꢎꢀꢵꢎꢐꢀꢵꢅꢣꢣꢓꢋꢅꢌꢀꢹꢎꢐꢀꢚꢅꢮꢓꢺꢝꢡꢌꢀꣀꢎꢐꢀꢹꢣꢓꢜꢅꢋꢫꢓꢐꢀꢞꢅꢣꢟꢋꢮꢅꢡꢌꢀꢥꢎꢐꢀꢴꢅꢆꢫꢆꢫꢓꢮꢅꢜꢅꢜꢮꢀ
ꢁꢂꢨꢃꢀ ꢑꢅꢜꢮꢅꢌꢀꢞꢎꢐꢀꢴꢅꢊꢅꢋꢓꢌꢀꢄꢎꢐꢀꢸꢅꢋꢅꢗꢒꢠꢒꢌꢀꢴꢎꢐꢀꢷꢅꢺꢅꢌꢀꢾꢎꢐꢀꢸꢅꢋꢅꢗꢟꢡꢅꢌꢀꢵꢎꢐꢀꢴꢫꢓꢡꢅꢊꢅꢙꢅꢌꢀꢷꢎꢐꢀ
ꢕꢋꢅꢗꢒꢠꢒꢌꢀꢷꢎꢐꢀꢾꢒꢋꢒꢊꢟꢋꢅꢌꢀꢕꢎꢀꢞꢫꢝꢀꢴꢓꢡꢠꢟꢓꢜꢀꢼꢜꢫꢓꢤꢓꢠꢒꢡꢀꢴꢓꢡꢠꢓꢜꢒꢣꢀꢼꢜꢫꢓꢤꢓꢠꢊꢀꢷꢝꢬꢅꢠꢓꢠꢓꢊꢀꢅꢀ꣇ꢓꢡꢟꢊꢀꢁꢷꢅꢯꢃꢀ
ꢄꢝꢬꢣꢓꢆꢅꢠꢓꢒꢜꢀꢤꢈꢀꢼꢜꢫꢓꢤꢓꢠꢓꢜꢺꢀꢷꢅꢯꢀꢼꢜꢠꢝꢡꢜꢅꢣꢀꢄꢓꢤꢒꢊꢒꢗꢅꢣꢀꢍꢜꢠꢡꢈꢀꢴꢓꢠꢝꢀꢹꢆꢠꢓꢯꢓꢠꢈꢎꢀ.ꢇꢈꢉꢀꢁꢂ .ꢇꢈꢊꢀꢋꢌ wꢁꢌ
/ꢈꢂꢂ"ꢓꢃꢀꢀꢁꢃꢂꢌꢀꢐ((ꢌꢀꢨꢩꢳꢎꢀ
ꢀ
ꢁꢂꢩꢃꢀ ꢛꢅꢙꢓꢜꢝꢆꢋꢓꢌꢀꢄꢎꢐꢀꢑꢟꢆꢇꢝꢋꢌꢀꢹꢎꢐꢀꢑꢒꢣꢝꢫꢗꢅꢓꢜꢝꢜꢌꢀꢍꢎꢐꢀꢕꢖꢗꢓꢅꢣꢒꢙꢊꢋꢓꢌꢀꢚꢎꢐꢀꢑꢡꢈꢺꢒꢙꢊꢋꢓꢌꢀꢞꢎꢀꢵꢎꢐꢀ
ꢑꢅꢟꢬꢬꢓꢜꢝꢜꢌꢀꢄꢎꢀꢼꢜꢰꢣꢟꢝꢜꢆꢝꢀꢒꢰꢀꢚꢒꢜꢮꢀꣁꢓꢱꢅꢠꢓꢒꢜꢀꢓꢜꢀꢚꢝꢜꢇꢒꢦꢹꢜꢜꢟꢣꢅꢠꢝꢮꢀꢸꢦꢴꢅꢣꢓꢆꢈꢣꢓꢮꢝꢜꢝꢅꢜꢓꢣꢓꢜꢝꢊꢀꢅꢜꢮꢀꢞꢫꢝꢓꢡꢀ
ꢕꢡꢠꢫꢒꢦꢭꢁ꣈ꢕꢃꣂꢀꢏꢝꢡꢓꢯꢅꢠꢓꢯꢝꢊꢀꢁꣂꢀ꣈ꢀꢭꢫꢧꢌꢀꢸꢫꢪꢌꢀꢕꢆꢫꢧꢃꢀꢒꢜꢀꢞꢅꢟꢠꢒꢗꢝꢡꢓꢆꢀꢍꢢꢟꢓꢣꢓꢤꢡꢓꢅꢀꢓꢜꢀꢴꢒꢣꢟꢠꢓꢒꢜꢎꢀW hꢒ+ /ꢀꢁꢂꢃꢀ
ꢀꢁꢁ ꢌꢀ'ꢑꢌꢀꢨꢨ꣄ꣅꢎꢀ
ꢀ
ꢁꢂꢳꢃꢀ ꣁꢓꢣꢅꢡꢒꢙꢊꢋꢓꢌꢀꢹꢎꢐꢀꢑꢒꢣꢣꢌꢀꢹꢎꢐꢀꢛꢣꢒꢙꢓꢅꢋꢌꢀꢞꢎꢀꢶꢒꢙꢀꢚꢅꢡꢡꢓꢝꢡꢀꢷꢈꢮꢡꢒꢺꢝꢜꢀꢚꢒꢜꢮꢊꢀꢓꢜꢀꢴꢠꢝꢡꢓꢆꢅꢣꢣꢈꢀ
ꢵꢒꢮꢓꢰꢓꢝꢮꢀꢴꢆꢫꢓꢰꢰꢀꢚꢅꢊꢝꢊꢎꢀWꢃ /ꢀꢁꢂꢃ {ꢈꢉꢃ. tꢁꢒ%ꢇꢓ Çꢒꢎꢓꢌꢃ ꢑꢀꢀꢁꢁꢀꢌꢀꣅꢧꢨꢎꢀ
ꢁꢂꣅꢃꢀ ꣁꢓꢣꢅꢡꢒꢙꢊꢋꢓꢌꢀꢹꢎꢀꢼꢜꢠꢡꢅꢗꢒꢣꢝꢆꢟꢣꢅꢡꢀꢷꢈꢮꢡꢒꢺꢝꢜꢀꢚꢒꢜꢮꢓꢜꢺꢀꢓꢜꢀꢕꢦꢷꢈꢮꢡꢒꢱꢈꢅꢡꢈꢣꢀꢴꢆꢫꢓꢰꢰꢀꢚꢅꢊꢝꢊꢠꢎꢀWꢃ
tꢀꢋꢌꢃ hꢒ+ꢃ /ꢀꢁꢂꢃꢀꢀꢁꢁꢂꢌꢀ ꢏꢌꢀꢩꣅꢩꢎꢀ
ꢁꢂ꣄ꢃꢀ ꣁꢓꢣꢅꢡꢒꢙꢊꢋꢓꢌꢀꢹꢎꢐꢀꢑꢒꢆꢫꢝꢣꢌꢀꢹꢎꢐꢀꢭꢓꢝꢊꢣꢓꢋꢌꢀꢑꢎꢐꢀꢑꢒꢣꢣꢌꢀꢹꢎꢀꢴꢠꢝꢡꢓꢆꢀꢅꢜꢮꢀꢹꢡꢒꢗꢅꢠꢓꢆꢀꢼꢗꢬꢅꢆꢠꢀꢒꢜꢀ
ꢀ
ꢀ
ꢼꢜꢠꢡꢅꢗꢒꢣꢝꢆꢟꢣꢅꢡꢀꢷꢈꢮꢡꢒꢺꢝꢜꢀꢚꢒꢜꢮꢊꢀꢓꢜꢀꢕꢦꢷꢈꢮꢡꢒꢱꢈꢅꢡꢈꢣꢀꢑꢝꢠꢒꢜꢝꢊꢀꢅꢜꢮꢀꢑꢝꢠꢓꢗꢓꢜꢝꢊꢎꢀWꢃ tꢀꢋꢌꢃ hꢒ+ꢃ /ꢀꢁꢂꢃꢀ
ꢀꢁꢁꢂꢌꢀ ꢏꢌꢀ꣄ꣅꢩꢎꢀ
ꢀ
ꢹꢊꢬꢝꢆꢠꢊꢀꢒꢰꢀꢞꢅꢟꢠꢒꢗꢝꢡꢓꢆꢀꢍꢢꢟꢓꢣꢓꢤꢡꢓꢟꢗꢀꢓꢜꢀꢷꢈꢮꢡꢒꢱꢈꢀꢹꢡꢈꢣꢀꢴꢆꢫꢓꢰꢰꢀꢚꢅꢊꢝꢊꢎꢀWꢃ tꢀꢋꢌꢃhꢒ+ꢃ /ꢀꢁꢂꢃꢀꢀꢁꢁꢆꢌꢀꢑ ꢌꢀ
꣄ꢧ꣄ꢎꢀ
ꢁꢪꢿꢃꢀ ꣁꢓꢣꢅꢡꢒꢙꢊꢋꢓꢌꢀꢹꢎꢐꢀꢑꢒꢆꢫꢝꢣꢌꢀꢹꢎꢐꢀꢑꢣꢟꢤꢅꢌꢀꢵꢎꢐꢀꢑꢅꢗꢒꢟꢜꢅꢫꢌꢀꣁꢎꢀꢴꢎꢀꢴꢠꢡꢟꢆꢠꢟꢡꢅꢣꢀꢅꢜꢮꢀꢹꢡꢒꢗꢅꢠꢓꢆꢀ
ꢀ
ꢁꢪꢂꢃꢀ ꢑꢡꢈꢺꢒꢙꢊꢋꢓꢌꢀꢞꢎꢀꢵꢎꢐꢀꢴꢇꢅꢠꢈꢣꢒꢙꢓꢆꢇꢌꢀꢷꢎꢐꢀꢴꢠꢅꢊꢈꢟꢋꢌꢀꢕꢎꢀꢹꢎꢐꢀꢏꢒꢗꢓꢜꢓꢋꢒꢙꢊꢋꢅꢌꢀꣀꢎꢐꢀꢥꢅꢣꢟꢊꢓꢅꢋꢌꢀꢵꢎꢀ
ꢹꢡꢒꢗꢅꢠꢓꢆꢓꢠꢈꢀꢰꢡꢒꢗꢀꢠꢫꢝꢀ꣇ꢓꢝꢙꢬꢒꢓꢜꢠꢀꢒꢰꢀꢵꢒꢣꢝꢆꢟꢣꢅꢡꢀꢛꢝꢒꢗꢝꢠꢡꢈꢻꢀꢹꢬꢬꢣꢓꢆꢅꢠꢓꢒꢜꢀꢠꢒꢀꢥꢣꢅꢜꢅꢡꢀꢴꢈꢊꢠꢝꢗꢊꢎꢀ/ꢀꢁꢂꢃ
wꢁꢄꢃꢀꢀꢁꢃꢇꢌꢀ ꢐꢌꢀꢩꢧꣅꢧꢎꢀ
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 21
1
2
3
4
5
6
ꢀ
ꢁꢪꢪꢃꢀ ꢑꢅꢡꢅꢤꢓꢈꢓꢋꢌꢀꢷꢎꢐꢀꢴꢝꢯꢓꢜ꣉ꢝꢋꢌꢀꢄꢎꢐꢀꢥꢝꢠꢝꢋꢌꢀꢷꢎꢐꢀꢹꢈꢺ꣊ꢜꢌꢀꢵꢎꢀꢹꢡꢒꢗꢅꢠꢓꢆꢓꢠꢈꢀꢚꢅꢣꢅꢜꢆꢝꢌꢀꢥꢓꢦꢍꢣꢝꢆꢠꢡꢒꢜꢀ
ꢭꢒꢒꢬꢝꢡꢅꢠꢓꢯꢓꢠꢈꢀꢅꢜꢮꢀꢷꢦꢚꢒꢜꢮꢓꢜꢺꢀꢥꢡꢒꢬꢝꢡꢠꢓꢝꢊꢀꢓꢜꢀꢞꢅꢟꢠꢒꢗꢝꢡꢓꢊꢗꢀꢒꢰꢀꢴꢅꢣꢓꢆꢈꢣꢓꢮꢝꢜꢝꢅꢜꢓꢣꢓꢜꢝꢻꢀꢞꢫꢝꢀ꣋ꢟꢅꢜꢠꢟꢗꢀ
ꢞꢫꢝꢒꢡꢈꢀꢒꢰꢀꢹꢠꢒꢗꢊꢀꢓꢜꢀꢵꢒꢣꢝꢆꢟꢣꢝꢊꢀꢁ꣋ꢠꢅꢓꢗꢃꢀꢹꢬꢬꢡꢒꢅꢆꢫꢎꢀWꢃ aꢈ#ꢃ aꢈꢔꢁ#ꢃ
ꢀꢀꢁꢃꢃꢌꢀ 'ꢌꢀꢂꢪ꣄ꢨꢎꢀ
7
8
9
ꢀ
ꢁꢪꢧꢃꢀ ꢛꢓꢣꢣꢓꢌꢀꢛꢎꢐꢀꢚꢝꢣꢣꢟꢆꢆꢓꢌꢀꣁꢎꢐꢀꣁꢝꢡꢡꢝꢠꢠꢓꢌꢀ꣇ꢎꢐꢀꢚꢝꢡꢠꢒꢣꢅꢊꢓꢌꢀ꣇ꢎꢀꢍꢯꢓꢮꢝꢜꢆꢝꢀꢰꢒꢡꢀꢄꢝꢊꢒꢜꢅꢜꢆꢝꢦꢹꢊꢊꢓꢊꢠꢝꢮꢀ
ꢷꢈꢮꢡꢒꢺꢝꢜꢦꢚꢒꢜꢮꢓꢜꢺꢀꢰꢡꢒꢗꢀꢭꢡꢈꢊꢠꢅꢣꢦꢴꢠꢡꢟꢆꢠꢟꢡꢝꢀꢭꢒꢡꢡꢝꢣꢅꢠꢓꢒꢜꢊꢀꢒꢜꢀꢠꢫꢝꢀꢍꢜꢒꢣꢀꣁꢒꢡꢗꢀꢒꢰꢀꢞꢫꢝꢀꢎꢚꢝꢠꢅꢎꢦꢏꢓꢋꢝꢠꢒꢜꢝꢀ
ꣁꢡꢅꢺꢗꢝꢜꢠꢎꢀWꢃ !ꢂꢃ /ꢀꢁꢂꢃ {ꢈꢉꢃꢀꢃꢅꢆꢅꢌꢀ ꢌꢀꢂꢿꢪꢧꢎꢀ
ꢁꢪꢽꢃꢀ ꢚꢝꢡꢠꢒꢣꢅꢊꢓꢌꢀ꣇ꢎꢐꢀꢛꢓꢣꢣꢓꢌꢀꢥꢎꢐꢀꣁꢝꢡꢡꢝꢠꢠꢓꢌꢀ꣇ꢎꢐꢀꢛꢓꢣꢣꢓꢌꢀꢛꢎꢀꢍꢯꢓꢮꢝꢜꢆꢝꢀꢰꢒꢡꢀꢄꢝꢊꢒꢜꢅꢜꢆꢝꢦꢹꢊꢊꢓꢊꢠꢝꢮꢀ
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ꢀ
ꢷꢈꢮꢡꢒꢺꢝꢜꢦꢚꢒꢜꢮꢓꢜꢺꢀꢎꢪꢎꢀꢼꢜꢠꢝꢡꢆꢒꢡꢡꢝꢣꢅꢠꢓꢒꢜꢀꢤꢝꢠꢙꢝꢝꢜꢀꢭꢡꢈꢊꢠꢅꢣꢦꢴꢠꢡꢟꢆꢠꢟꢡꢝꢀꢅꢜꢮꢀꢴꢬꢝꢆꢠꢡꢒꢊꢆꢒꢬꢓꢆꢀꢥꢅꢡꢅꢗꢝꢠꢝꢡꢊꢀ
ꢓꢜꢀꣅꢀꢼꢜꢠꢡꢅꢗꢒꢣꢝꢆꢟꢣꢅꢡꢣꢈꢀꢷꢈꢮꢡꢒꢺꢝꢜꢦꢚꢒꢜꢮꢝꢮꢀꢂꢌꢧꢦꢏꢓꢅꢡꢈꢣꢦꢂꢌꢧꢦꢥꢡꢒꢬꢅꢜꢝꢮꢓꢒꢜꢝꢀꢍꢜꢒꢣꢊꢎꢀWꢃ !ꢂꢃ /ꢀꢁꢂꢃ {ꢈꢉꢃꢀ
ꢃꢅꢅꢃꢌꢀ ꢌꢀꢽ꣄ꢂꢳꢎꢀ
ꢀ
ꢁꢪꢨꢃꢀ ꢛꢓꢣꢣꢓꢌꢀꢥꢎꢐꢀꢚꢝꢡꢠꢒꢣꢅꢊꢓꢌꢀ꣇ꢎꢐꢀꣁꢝꢡꢡꢝꢠꢠꢓꢌꢀ꣇ꢎꢐꢀꢛꢓꢣꢣꢓꢌꢀꢛꢎꢀꢍꢯꢓꢮꢝꢜꢆꢝꢀꢰꢒꢡꢀꢼꢜꢠꢡꢅꢗꢒꢣꢝꢆꢟꢣꢅꢡꢀꢸ−ꢷ···ꢕꢀ
ꢄꢝꢊꢒꢜꢅꢜꢆꢝꢦꢹꢊꢊꢓꢊꢠꢝꢮꢀꢷꢈꢮꢡꢒꢺꢝꢜꢀꢚꢒꢜꢮꢓꢜꢺꢀꢓꢜꢀ꣌ꢦꢍꢜꢅꢗꢓꢜꢒꢜꢝꢊꢀꢅꢜꢮꢀꢄꢝꢣꢅꢠꢝꢮꢀꢷꢝꢠꢝꢡꢒꢮꢓꢝꢜꢝꢊꢎꢀꢹꢀ
ꢭꢒꢗꢤꢓꢜꢝꢮꢀꢭꢡꢈꢊꢠꢅꢣꢦꢴꢠꢡꢟꢆꢠꢟꢡꢅꢣꢌꢀꢼꢡꢀꢅꢜꢮꢀꢸꢗꢡꢀꢴꢬꢝꢆꢠꢡꢒꢊꢆꢒꢬꢓꢆꢌꢀꢅꢜꢮꢀ꣋ꢟꢅꢜꢠꢟꢗꢦꢵꢝꢆꢫꢅꢜꢓꢆꢅꢣꢀꢼꢜꢯꢝꢊꢠꢓꢺꢅꢠꢓꢒꢜꢎꢀ
Wꢃ !ꢂꢃ /ꢀꢁꢂꢃ {ꢈꢉꢃꢀꢀꢁꢁꢁꢌꢀ ꢑꢑꢌꢀꢂꢿꢽꢿꢨꢎꢀ
ꢀ
ꢁꢪꢩꢃꢀ ꢵꢅꢫꢗꢟꢮꢒꢯꢌꢀꢑꢎꢀꢞꢎꢐꢀꢥꢒꢗꢤꢝꢓꢡꢒꢌꢀꢹꢎꢀꣀꢎꢀꢶꢎꢀꢄꢝꢊꢒꢜꢅꢜꢆꢝꢦꢹꢊꢊꢓꢊꢠꢝꢮꢀꢷꢈꢮꢡꢒꢺꢝꢜꢀꢚꢒꢜꢮꢓꢜꢺꢀꢅꢊꢀꢅꢀ
ꢏꢡꢓꢯꢓꢜꢺꢀꣁꢒꢡꢆꢝꢀꢓꢜꢀꢴꢈꢜꢠꢫꢝꢊꢓꢊꢀꢅꢜꢮꢀꢅꢀꢴꢈꢜꢠꢫꢒꢜꢀꢓꢜꢀꢠꢫꢝꢀꢏꢝꢊꢓꢺꢜꢀꢒꢰꢀꢵꢅꢠꢝꢡꢓꢅꢣꢊꢎꢀ/ꢀꢁꢂꢃ 9"ꢒꢃ Wꢃꢀꢀꢁꢃꢄꢌꢀꢑꢑꢌꢀ
ꢂꢩꢧꢨꢩꢎꢀ
ꢀ
ꢀ
ꢰꢡꢒꢗꢀꢹꢆꢓꢮꢦꢚꢅꢊꢝꢀꢵꢒꢣꢝꢆꢟꢣꢅꢡꢀꢥꢡꢒꢬꢝꢡꢠꢓꢝꢊꢎꢀꢞꢫꢝꢀꢥꢋꢁꢅꢃꢀꢴꢣꢓꢮꢝꢀꢄꢟꢣꢝꢻꢀꢞꢒꢙꢅꢡꢮꢀꢠꢫꢝꢀꢴꢒꢣꢟꢠꢓꢒꢜꢀꢒꢰꢀꢅꢀꢶꢒꢜꢺꢦ
ꢶꢅꢊꢠꢓꢜꢺꢀꢥꢡꢒꢤꢣꢝꢗꢎꢀ!ꢉꢉ /ꢀꢁꢂ wꢁꢌꢀꢀꢁꢁꢅꢌꢀꢐꢑꢌꢀꢧꢧꢎꢀ
ꢀ
ꢁꢪꢳꢃꢀ ꢴꢅꢜꢇꢌꢀꢥꢎꢐꢀꢵ꣍ꢌꢀꢕꢎꢐꢀꢾ꣎꣏ꢝꢇꢌꢀꢵꢎꢐꢀꢍꢣꢺꢟꢝꢡꢒꢌꢀꣀꢎꢀWꢃ tꢀꢋꢌꢃ /ꢀꢁꢂꢃ !ꢀꢀꢁꢁ ꢌꢀ
ꢌꢀꢧꢨꣅꢨꢎꢀ
ꢁꢪꣅꢃꢀ ꢛꢓꢣꢣꢓꢌꢀꢥꢎꢐꢀꢥꢡꢝꢠꢠꢒꢌꢀꢶꢎꢐꢀꢚꢝꢡꢠꢒꢣꢅꢊꢓꢌꢀ꣇ꢎꢐꢀꢛꢓꢣꢣꢓꢌꢀꢛꢎꢀꢥꢡꢝꢮꢓꢆꢠꢓꢜꢺꢀꢷꢈꢮꢡꢒꢺꢝꢜꢦꢚꢒꢜꢮꢀꢴꢠꢡꢝꢜꢺꢠꢫꢊꢀ
ꢁꢪ꣄ꢃꢀ ꣐ꢟꢤꢅꢠꢈꢟꢋꢌꢀꢄꢎꢀꢼꢎꢐꢀ꣇ꢒꢣꢒꢯꢝꢜꢋꢒꢌꢀꢾꢎꢀꢵꢎꢐꢀꢴꢫꢓꢊꢫꢋꢓꢜꢌꢀꢕꢎꢀ꣇ꢎꢐꢀꢛꢒꢡꢤꢌꢀꢶꢎꢐꢀꢶꢝꢊꢇꢆꢇꢈꢜꢊꢋꢓꢌꢀꣀꢎꢀ
ꢹꢡꢒꢗꢅꢠꢓꢆꢓꢠꢈꢦꢭꢒꢜꢠꢡꢒꢣꢣꢝꢮꢀꢞꢅꢟꢠꢒꢗꢝꢡꢓꢊꢗꢀꢅꢜꢮꢀꢄꢝꢊꢒꢜꢅꢜꢆꢝꢦꢹꢊꢊꢓꢊꢠꢝꢮꢀꢷꢈꢮꢡꢒꢺꢝꢜꢀꢚꢒꢜꢮꢓꢜꢺꢀꢓꢜꢀꢷꢝꢠꢝꢡꢒꢆꢈꢆꢣꢓꢆꢀ
ꢍꢜꢅꢗꢓꢜꢒꢜꢝꢦꢼꢗꢓꢜꢒꢝꢜꢒꢣꢀꢴꢈꢊꢠꢝꢗꢊꢎꢀWꢃ hꢒ+ꢃ /ꢀꢁꢂꢃꢀꢀꢁꢁ ꢌꢀ'ꢑꢌꢀꢳꢪꢨꢎꢀ
ꢀ
ꢁꢧꢿꢃꢀ ꢑꢡꢈꢺꢒꢙꢊꢋꢓꢌꢀꢞꢎꢀꢵꢎꢐꢀꢚꢅꢜꢋꢓꢝꢙꢓꢆꢇꢌꢀꢚꢎꢐꢀꢭꢇꢅꢡꢜꢒꢆꢋꢓꢌꢀ꣐ꢎꢐꢀꢥꢅꢣꢟꢊꢓꢅꢋꢌꢀꢵꢎꢀ꣋ꢟꢅꢊꢓꢦꢹꢡꢒꢗꢅꢠꢓꢆꢓꢠꢈꢦ
ꢔꢫꢅꢠꢀꢏꢒꢝꢊꢀꢼꢠꢀꢵꢝꢅꢜ꣑ꢀÇꢁꢍꢒꢎꢀꢁꢔꢒꢈꢓꢀꢀꢁꢃꢂꢌꢀ' ꢌꢀꢽꣅ꣄ꢨꢎꢀ
ꢁꢧꢂꢃꢀ ꢛꢟꢠꢓꢝꢡꢡꢝꢇꢦꢹꢡꢇꢅꢣꢟꢇꢌꢀꢶꢎꢐꢀꢭꢒꢡꢠꢝꢊꢦꢛꢟꢇꢗꢅꢜꢌꢀꣁꢎꢐꢀꢄꢒꢆꢫꢅꢦꢄꢓꢜꢇꢅꢌꢀꢞꢎꢐꢀꢥꢝꢒꢜꢌꢀꣀꢎꢀ꣒ꢣꢠꢡꢅꢰꢅꢊꢠꢀ
ꢀ
ꢍꢱꢆꢓꢠꢝꢮꢀꢴꢠꢅꢠꢝꢀꢷꢈꢮꢡꢒꢺꢝꢜꢀꢹꢠꢒꢗꢀꢞꢡꢅꢜꢊꢰꢝꢡꢀꢓꢜꢀꢴꢅꢣꢓꢆꢈꢣꢓꢮꢝꢜꢝꢅꢜꢓꢣꢓꢜꢝꢀꢏꢡꢓꢯꢝꢜꢀꢤꢈꢀꢭꢫꢅꢜꢺꢝꢊꢀꢓꢜꢀꢹꢡꢒꢗꢅꢠꢓꢆꢓꢠꢈꢎꢀ
tꢀꢋꢌꢃ /ꢀꢁꢂꢃ /ꢀꢁꢂꢃ tꢀꢋꢌꢃꢀꢀꢁꢃꢂꢌꢀ 'ꢌꢀꢧꢂꢩꢿꣅꢎꢀ
ꢀ
ꢛꢅꢙꢓꢜꢝꢆꢋꢓꢌꢀꢄꢎꢀꢴꢟꢤꢊꢠꢓꢠꢟꢝꢜꢠꢀꢅꢜꢮꢀꢞꢝꢗꢬꢝꢡꢅꢠꢟꢡꢝꢀꢭꢒꢜꢠꢡꢒꢣꢣꢝꢮꢀꢞꢅꢟꢠꢒꢗꢝꢡꢓꢊꢗꢻꢀꢵꢟꢣꢠꢓꢜꢟꢆꢣꢝꢅꢡꢀꢵꢅꢺꢜꢝꢠꢓꢆꢀ
ꢄꢝꢊꢒꢜꢅꢜꢆꢝꢌꢀꣂꢦꢄꢅꢈꢌꢀꢅꢜꢮꢀꢞꢫꢝꢒꢡꢝꢠꢓꢆꢅꢣꢀꢴꢠꢟꢮꢓꢝꢊꢀꢒꢜꢀꢪꢦꢥꢫꢝꢜꢅꢆꢈꢣꢢꢟꢓꢜꢒꢣꢓꢜꢝꢊꢎꢀWꢈ"ꢒꢓꢎ# ꢈ0 ꢍꢀꢁ /ꢀꢁꢂꢇꢉꢎ#
{ꢈꢉꢇꢁꢍꢋ1tꢁꢒ%ꢇꢓ Çꢒꢎꢓꢌꢎꢉꢍꢇꢈꢓꢌ ꢑꢀꢀꢁꢁꢁꢌꢀ(ꢌꢀꢂꢪꢨ꣄ꢎꢀ
ꢁꢧꢪꢃꢀ ꢑꢒꢣꢝꢫꢗꢅꢓꢜꢝꢜꢌꢀꢍꢎꢐꢀꢕꢊꢗꢓꢅꢣꢒꢙꢊꢋꢓꢌꢀꢚꢎꢐꢀꢑꢡꢈꢺꢒꢙꢊꢋꢓꢌꢀꢞꢎꢀꢵꢎꢐꢀꢑꢅꢟꢬꢬꢓꢜꢝꢜꢌꢀꢄꢎꢐꢀꢸꢓꢊꢊꢓꢜꢝꢜꢌꢀꢵꢎꢐꢀ
ꢀ
ꢁꢧꢧꢃꢀ ꢑꢒꢣꢝꢫꢗꢅꢓꢜꢝꢜꢌꢀꢍꢎꢐꢀꢕꢊꢗꢓꢅꢣꢒꢙꢊꢋꢓꢌꢀꢚꢎꢐꢀꢸꢓꢊꢊꢓꢜꢝꢜꢌꢀꢵꢎꢐꢀꢑꢅꢟꢬꢬꢓꢜꢝꢜꢌꢀꢄꢎꢐꢀꢛꢅꢙꢓꢜꢝꢆꢋꢓꢌꢀꢄꢎꢀ
ꢴꢟꢤꢊꢠꢓꢠꢟꢝꢜꢠꢀꢅꢜꢮꢀꢞꢝꢗꢬꢝꢡꢅꢠꢟꢡꢝꢀꢭꢒꢜꢠꢡꢒꢣꢣꢝꢮꢀꢞꢅꢟꢠꢒꢗꢝꢡꢓꢊꢗꢀꢒꢰꢀꢪꢦꢥꢫꢝꢜꢅꢆꢈꢣꢬꢈꢡꢓꢮꢓꢜꢝꢻꢀꢞꢫꢝꢀꢷꢈꢮꢡꢒꢺꢝꢜꢀ
ꢚꢒꢜꢮꢀꢅꢊꢀꢅꢀꢭꢒꢜꢰꢓꢺꢟꢡꢅꢠꢓꢒꢜꢅꢣꢀꢶꢒꢆꢋꢀꢒꢰꢀꢁ꣐ꢃꢦꢪꢦꢁꢪꢦꢷꢈꢮꢡꢒꢱꢈꢦꢪꢦꢥꢫꢝꢜꢈꢣꢯꢓꢜꢈꢣꢃꢥꢈꢡꢓꢮꢓꢜꢝꢎꢀWꢃ /ꢀꢁꢂꢃ {ꢈꢉꢃ. tꢁꢒ%ꢇꢓ
Çꢒꢎꢓꢌꢃ ꢑꢀꢀꢁꢁꢁꢌꢀꢪꢂꣅꢨꢎꢀ
ꢀ
ꢁꢧꢽꢃꢀ ꢛꢅꢙꢓꢜꢝꢆꢋꢓꢌꢀꢄꢎꢐꢀꢑꢒꢣꢝꢫꢗꢅꢓꢜꢝꢜꢌꢀꢍꢎꢐꢀꢶꢒꢺꢫꢗꢅꢜꢓꢦꢑꢫꢒꢟꢇꢅꢜꢓꢌꢀꢷꢎꢐꢀꢕꢊꢗꢓꢅꢣꢒꢙꢊꢋꢓꢌꢀꢚꢎꢐꢀꢶꢒꢯꢅꢊꢇꢌꢀ
ꢞꢎꢐꢀꢄꢒꢊꢅꢌꢀꢥꢎꢀꢍꢰꢰꢝꢆꢠꢀꢒꢰꢀꢥꢓꢦꢍꢣꢝꢆꢠꢡꢒꢜꢀꢏꢝꢣꢒꢆꢅꢣꢓꢇꢅꢠꢓꢒꢜꢀꢒꢜꢀꢞꢅꢟꢠꢒꢗꢝꢡꢓꢆꢀꢍꢢꢟꢓꢣꢓꢤꢡꢓꢅꢀꢦꢀꢚꢝꢜꢇꢒꢅꢜꢜꢟꢣꢅꢠꢝꢮꢀꢪꢦ
ꢥꢫꢝꢜꢅꢆꢈꢣꢬꢈꢡꢓꢮꢓꢜꢝꢊꢎꢀ9"ꢒꢃ Wꢃ hꢒ+ /ꢀꢁꢂꢃꢀꢀꢁꢁꢄꢌꢀꢪꣅꢂꢳꢎꢀ
ꢀ
ꢁꢧꢨꢃꢀ ꢛꢓꢣꢣꢓꢌꢀꢥꢎꢐꢀꢛꢓꢣꢣꢓꢌꢀꢛꢎꢀꢷꢈꢮꢡꢒꢺꢝꢜꢀꢚꢒꢜꢮꢀꢵꢒꢮꢝꢣꢊꢀꢅꢜꢮꢀꢞꢫꢝꢒꢡꢓꢝꢊꢻꢀꢞꢫꢝꢀꢏꢟꢅꢣꢀꢷꢈꢮꢡꢒꢺꢝꢜꢀꢚꢒꢜꢮꢀ
ꢵꢒꢮꢝꢣꢀꢅꢜꢮꢀꢼꢠꢊꢀꢭꢒꢜꢊꢝꢢꢟꢝꢜꢆꢝꢊꢎꢀW aꢈ# {ꢍꢒ"ꢉꢍꢀꢀꢁꢃꢁꢌꢀ,'ꢑꢌꢀꢪꢎꢀ
ACS Paragon Plus Environment

Page 19 of 21
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
ꢀ
ꢁꢧꢩꢃꢀ ꢵꢅꢡꢠꢓꢜꢝꢇꢌꢀꢭꢎꢀꢷꢎꢐꢀꢏꢅꢡꢮꢒꢜꢯꢓꢣꢣꢝꢌꢀꢭꢎꢀꢄꢅꢬꢓꢮꢀꢏꢝꢠꢝꢡꢗꢓꢜꢅꢠꢓꢒꢜꢀꢒꢰꢀꢼꢒꢜꢓꢇꢅꢠꢓꢒꢜꢀꢭꢒꢜꢊꢠꢅꢜꢠꢊꢀꢁꢥꢋꢀ
ꢅꢃꢀꢤꢈꢀ꣒ꢯꢀꢴꢬꢝꢆꢠꢡꢒꢊꢆꢒꢬꢈꢀ꣒ꢊꢓꢜꢺꢀ꣄ꢩꢦꢔꢝꢣꢣꢀꢵꢓꢆꢡꢒꢠꢓꢠꢝꢡꢀꢥꢣꢅꢠꢝꢊꢎꢀ!/{ aꢁꢔꢃ /ꢀꢁꢂꢃ [ꢁꢍꢍꢃꢀꢀꢁꢃꢈꢌꢀꢐꢌꢀꢂꢽꢪꢎꢀ
ꢁꢧꢳꢃꢀ ꢏꢝꢣꢬꢓꢯꢒꢌꢀꢭꢎꢐꢀꢵꢓꢆꢫꢝꢣꢝꢠꢠꢓꢌꢀꢛꢎꢐꢀꢚꢒꢺꢅꢌꢀꢭꢎꢀꢹꢀꢛꢡꢝꢝꢜꢀꢴꢈꢜꢠꢫꢝꢊꢓꢊꢀꢒꢰꢀ꣋ꢟꢓꢜꢒꢱꢅꢣꢓꢜꢝꢊꢀꢅꢜꢮꢀꢪꢌꢧꢦ
ꢏꢓꢫꢈꢮꢡꢒꢬꢈꢡꢅꢇꢓꢜꢝꢊꢎꢀ{ꢋꢓꢍꢀꢁꢌꢇꢌꢀꢀꢁꢃꢈꢌꢀꢐꢆꢌꢀꢂꢨꢽꢩꢎꢀ
ꢁꢧꣅꢃꢀ ꢾꢅꢊꢟꢮꢅꢌꢀꢷꢎꢐꢀꢏꢒꢗꢓꢠꢡꢒꢯꢓꢆꢫꢌꢀꢕꢎꢀ꣇ꢎꢀꢀ꣒ꢴꢎꢀꢥꢅꢠꢎꢀꢹꢬꢬꢣꢎꢀꢪꢿꢿ꣄ꢿꢂꢽ꣄ꢩꢳꢩꢀꢥꢟꢤꢣꢌꢀ꣒ꢴꢂꢪꢧꢪꢳꢨꢿꢩꢌꢀ
ꣀꢟꢜꢝꢀꢂꢂꢌꢀꢪꢿꢿ꣄ꢎꢀ
ꢀ
ꢀ
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ꢀ
ꢁꢧ꣄ꢃꢀ ꢭꢫꢝꢟꢜꢺꢌꢀꢭꢎꢀꢔꢎꢐꢀꢚꢟꢆꢫꢙꢅꢣꢮꢌꢀꢴꢎꢀꢶꢎꢀꢥꢅꢣꢣꢅꢮꢓꢟꢗꢦꢭꢅꢠꢅꢣꢈꢇꢝꢮꢀꢷꢈꢮꢡꢒꢱꢈꢣꢅꢠꢓꢒꢜꢀꢒꢰꢀꢹꢡꢈꢣꢀꢅꢜꢮꢀ
ꢷꢝꢠꢝꢡꢒꢅꢡꢈꢣꢀꢷꢅꢣꢓꢮꢝꢊꢀꢍꢜꢅꢤꢣꢝꢮꢀꢤꢈꢀꢠꢫꢝꢀ꣒ꢊꢝꢀꢒꢰꢀꢅꢀꢥꢅꢣꢣꢅꢮꢅꢆꢈꢆꢣꢝꢀꢥꢡꢝꢆꢅꢠꢅꢣꢈꢊꢠꢎꢀWꢃ hꢒ+ꢃ /ꢀꢁꢂꢃꢀꢀꢁꢃꢇꢌꢀ',ꢌꢀ
ꢨꢧꢨꢂꢎꢀ
ꢀ
ꢀ
ꢀ
ꢁꢽꢿꢃꢀ ꢔꢈꢜꢤꢝꢡꢺꢌꢀꢷꢎꢀꢞꢫꢝꢀꢄꢝꢓꢗꢝꢡꢦꢞꢓꢝꢗꢅꢜꢜꢀꢄꢝꢅꢆꢠꢓꢒꢜꢎꢀ/ꢀꢁꢂꢃ wꢁꢄꢃꢀꢃꢅꢄꢁꢌꢀ(ꢅꢌꢀꢂꢩ꣄ꢎꢀ
ꢁꢽꢂꢃꢀ ꣁꢝꢡꢺꢟꢊꢒꢜꢌꢀꢶꢎꢀꢸꢎꢀꢞꢫꢝꢀꢴꢈꢜꢠꢫꢝꢊꢓꢊꢀꢒꢰꢀꢹꢡꢒꢗꢅꢠꢓꢆꢀꢹꢣꢮꢝꢫꢈꢮꢝꢊꢎꢀ/ꢀꢁꢂꢃ wꢁꢄꢃꢀꢃꢅꢇꢄꢌꢀ ꢏꢌꢀꢪꢪꢳꢎꢀ
ꢁꢽꢪꢃꢀ ꢴꢋꢒꢜꢓꢝꢆꢇꢜꢈꢌꢀꢑꢎꢐꢀꢭꢫꢅꢡꢅꢣꢅꢗꢤꢓꢮꢓꢊꢌꢀꢛꢎꢐꢀꢞꢅꢊꢓꢒꢡꢌꢀꢵꢎꢐꢀꢑꢡꢇꢝꢊꢇꢝꢙꢊꢋꢓꢌꢀꢵꢎꢐꢀꢑꢅꢣꢋꢅꢜꢦꢚꢟꢡꢅꢠꢌꢀꢹꢎꢐꢀ
ꢭꢒꢟꢠꢊꢒꢣꢝꢣꢒꢊꢌꢀꢹꢎꢀꢛꢎꢐꢀꢛꢡꢈꢋꢒꢌꢀꢏꢎꢀꢞꢎꢀꢛꢝꢜꢝꢡꢅꢣꢀꢅꢜꢮꢀꢍꢰꢰꢓꢆꢓꢝꢜꢠꢀꢥꢡꢒꢠꢒꢆꢒꢣꢀꢰꢒꢡꢀꣁꢒꢡꢗꢈꢣꢅꢠꢓꢒꢜꢀꢒꢰꢀꢹꢡꢒꢗꢅꢠꢓꢆꢀꢅꢜꢮꢀ
ꢷꢝꢠꢝꢡꢒꢆꢈꢆꢣꢓꢆꢀꢥꢫꢝꢜꢒꢣꢊꢎꢀ{ꢋꢓꢍꢀꢁꢌꢇꢌꢀꢀꢁꢃꢀꢌꢀꢐꢐꢌꢀꢧꢩꣅꢧꢎꢀ
ꢀ
ꢁꢽꢧꢃꢀ ꢔꢓꢠꢅꢜꢒꢙꢊꢋꢓꢌꢀꢵꢎꢐꢀꢴꢠꢝꢰꢅꢜꢓꢅꢋꢌꢀꢶꢎꢐꢀꢔꢝꢤꢤꢌꢀꢛꢎꢀꢹꢎꢀꢸꢓꢠꢡꢒꢺꢝꢜꢀꢸꢗꢡꢀꢴꢬꢝꢆꢠꢡꢒꢊꢆꢒꢬꢈꢎꢀ!ꢓꢓ"ꢃ
wꢁꢊꢃ baw {ꢊꢁꢉꢍꢒꢈꢌꢉꢃꢀꢃꢅꢅꢈꢌꢀꢑꢆꢌꢀꢂꢎꢀ
ꢁꢽꢽꢃꢀ ꢴꢅꢣꢗꢅꢜꢌꢀꢴꢎꢀꢄꢎꢐꢀꢶꢓꢜꢮꢒꢜꢌꢀꣀꢎꢀꢭꢎꢐꢀꣁꢅꢡꢡꢅꢜꢠꢌꢀꢄꢎꢀꢏꢎꢐꢀꢭꢅꢡꢬꢝꢜꢠꢝꢡꢌꢀꢞꢎꢀꢹꢎꢀꢞꢅꢟꢠꢒꢗꢝꢡꢓꢊꢗꢀꢓꢜꢀꢪꢦ
ꢀ
ꢷꢈꢮꢡꢒꢱꢈꢦꢶꢦꢸꢅꢬꢫꢠꢫꢅꢣꢮꢝꢫꢈꢮꢝꢀꢴꢆꢫꢓꢰꢰꢦꢚꢅꢊꢝꢊꢀꢓꢜꢀꢴꢒꢣꢟꢠꢓꢒꢜꢀꢅꢜꢮꢀꢠꢫꢝꢀꢴꢒꢣꢓꢮꢦꢴꢠꢅꢠꢝꢀꢼꢜꢯꢝꢊꢠꢓꢺꢅꢠꢝꢮꢀ꣒ꢊꢓꢜꢺꢀꢭꢦꢂꢧꢀ
ꢸꢗꢡꢦꢴꢬꢝꢆꢠꢡꢒꢊꢆꢒꢬꢈꢎꢀaꢎ+ꢓꢁꢍꢇꢉ wꢁꢌꢈꢓꢎꢓꢉꢁ ꢇꢓ /ꢀꢁꢂꢇꢌꢍꢒꢋꢀꢃꢅꢅꢈꢌꢀ ꢌꢀ꣄꣄ꢂꢎꢀ
ꢀ
ꢁꢽꢨꢃꢀ ꢑꢅꢊꢆꢫꢝꢡꢝꢊꢌꢀꢭꢎꢀꢵꢎꢀꢞꢫꢝꢀꢭꢫꢝꢗꢓꢊꢠꢡꢈꢀꢒꢰꢀꢍꢜꢅꢗꢓꢜꢒꢜꢝꢊꢌꢀꢏꢓꢅꢇꢒꢆꢅꢡꢤꢒꢜꢈꢣꢊꢀꢅꢜꢮꢀꢴꢗꢅꢣꢣꢀꢄꢓꢜꢺꢊꢻꢀ
ꢕꢟꢡꢀꢭꢒꢜꢠꢡꢓꢤꢟꢠꢓꢒꢜꢎꢀWꢃ .ꢒꢎ4ꢃ /ꢀꢁꢂꢃ {ꢈꢉꢃꢀꢀꢁꢁꢈꢌꢀ ꢐꢌꢀ꣄ꢽꢨꢎꢀ
ꢁꢽꢩꢃꢀ ꢕꢺꢅꢙꢅꢌꢀꢑꢎꢐꢀꢷꢅꢡꢅꢮꢅꢌꢀꣀꢎꢀꢹꢺꢺꢡꢝꢺꢅꢠꢓꢒꢜꢀꢭꢒꢜꢠꢡꢒꢣꢣꢝꢮꢀꢥꢡꢒꢠꢒꢜꢀꢞꢅꢟꢠꢒꢗꢝꢡꢓꢇꢅꢠꢓꢒꢜꢀꢓꢜꢀ
ꢴꢅꢣꢓꢆꢈꢣꢓꢮꢝꢜꢝꢅꢜꢓꢣꢓꢜꢝꢊꢎꢀW aꢈ# {ꢍꢒ"ꢉꢍꢀꢀꢁꢁꢈꢌꢀ(ꢐ'ꢌꢀꢪꢂꢂꢎꢀ
ꢁꢽꢳꢃꢀ ꢚꢟꢝꢗꢓꢌꢀꢛꢎꢐꢀ꣐ꢟꢆꢆꢅꢡꢝꢣꢣꢒꢌꢀꣁꢎꢐꢀ꣇ꢝꢜꢟꢯꢅꢜꢅꢣꢓꢜꢺꢅꢗꢌꢀꢥꢎꢐꢀꢄꢅꢗꢅꢣꢓꢜꢺꢅꢗꢌꢀꢵꢎꢀꢹꢤꢀꢼꢜꢓꢠꢓꢒꢀꢴꢠꢟꢮꢈꢀꢒꢰꢀ
ꢀ
ꢀ
ꢞꢅꢟꢠꢒꢗꢝꢡꢓꢊꢗꢀꢅꢜꢮꢀꢷꢈꢮꢡꢒꢺꢝꢜꢀꢚꢒꢜꢮꢓꢜꢺꢀꢒꢰꢀꢚꢝꢠꢅꢦꢭꢅꢡꢤꢒꢜꢈꢣꢅꢗꢓꢜꢝꢀꢓꢜꢀꢠꢫꢝꢀꢛꢅꢊꢀꢥꢫꢅꢊꢝꢀꢅꢜꢮꢀꢓꢜꢀꢔꢅꢠꢝꢡꢀ
ꢴꢒꢣꢟꢠꢓꢒꢜꢎꢀÇꢀꢁꢈꢒ /ꢀꢁꢂ !ꢉꢉꢀꢀꢁꢁꢁꢌꢀ ꢅꢐꢌꢀꢪꢪꢩꢎꢀ
ꢀ
ꢅꢜꢮꢀꢵꢒꢣꢝꢆꢟꢣꢅꢡꢀꢴꢠꢡꢟꢆꢠꢟꢡꢝꢊꢀꢒꢰꢀꢸꢝꢙꢀꢭꢫꢡꢒꢗꢒꢜꢝꢀꢏꢝꢡꢓꢯꢅꢠꢓꢯꢝꢊꢀꢅꢊꢀꢍꢗꢬꢓꢡꢓꢆꢅꢣꢀꢍꢯꢓꢮꢝꢜꢆꢝꢀꢒꢰꢀꢼꢜꢠꢡꢅꢗꢒꢣꢝꢆꢟꢣꢅꢡꢀ
ꢥꢡꢒꢠꢒꢜꢀꢞꢡꢅꢜꢊꢰꢝꢡꢀꢄꢝꢅꢆꢠꢓꢒꢜꢐꢀꢹꢤꢀꢼꢜꢓꢠꢓꢒꢀꢴꢠꢟꢮꢓꢝꢊꢀꢒꢜꢀꢼꢜꢠꢡꢅꢗꢒꢣꢝꢆꢟꢣꢅꢡꢀꢷꢦꢚꢒꢜꢮꢊꢀꢓꢜꢀꢍꢜꢅꢗꢓꢜꢒꢜꢝꢊꢎꢀWꢃ tꢀꢋꢌꢃ
/ꢀꢁꢂꢃ !ꢀꢀꢁꢁꢀꢌꢀ ꢅ(ꢌꢀꢂꢂ꣄ꢨꢩꢎꢀ
ꢁꢽꣅꢃꢀ ꢄꢈꢤꢅꢡꢆꢇꢈꢋꢦꢥꢓꢡꢝꢋꢌꢀꢹꢎꢀꣀꢎꢐꢀꢛꢡꢅꢤꢒꢙꢊꢋꢓꢌꢀꢴꢎꢀꣀꢎꢐꢀꢵꢅꢣꢝꢆꢋꢅꢌꢀꢵꢎꢐꢀꢸꢅꢙꢡꢒꢠꢦꢵꢒꢮꢡꢅꢜꢋꢅꢌꢀꣀꢎꢀꢭꢡꢈꢊꢠꢅꢣꢀ
ꢀ
ꢁꢽ꣄ꢃꢀ ꢕꢺꢅꢙꢅꢌꢀꢑꢎꢐꢀꢑꢅꢊꢅꢫꢅꢡꢅꢌꢀꢾꢎꢐꢀꢕꢫꢠꢅꢜꢓꢌꢀꢾꢎꢐꢀꢷꢅꢡꢅꢮꢅꢌꢀꣀꢎꢀꢭꢡꢈꢊꢠꢅꢣꢀꢴꢠꢡꢟꢆꢠꢟꢡꢝꢀꢭꢫꢅꢜꢺꢝꢀꢰꢒꢡꢀꢠꢫꢝꢀ
ꢞꢫꢝꢡꢗꢒꢆꢫꢡꢒꢗꢈꢀꢒꢰꢀꢸꢦꢴꢅꢣꢓꢆꢈꢣꢓꢮꢝꢜꢝꢅꢜꢓꢣꢓꢜꢝꢊꢎꢀꢞꢫꢝꢀꣁꢓꢡꢊꢠꢀꢕꢤꢊꢝꢡꢯꢅꢠꢓꢒꢜꢀꢤꢈꢀꣂꢦꢄꢅꢈꢀꢏꢓꢰꢰꢡꢅꢆꢠꢓꢒꢜꢎꢀWꢃ !ꢂꢃ
/ꢀꢁꢂꢃ {ꢈꢉꢃꢀꢃꢅꢅꢆꢌꢀ ꢑꢅꢌꢀꢳꢂꢿꢳꢎꢀ
ꢀ
ꢅꢜꢮꢀꢴꢒꢣꢯꢝꢜꢠꢀꢍꢰꢰꢝꢆꢠꢀꢒꢜꢀꢞꢅꢟꢠꢒꢗꢝꢡꢓꢆꢀꢍꢢꢟꢓꢣꢓꢤꢡꢓꢟꢗꢀꢓꢜꢀꢴꢆꢫꢓꢰꢰꢀꢚꢅꢊꢝꢀꢏꢝꢡꢓꢯꢝꢮꢀꢰꢡꢒꢗꢀꢪꢦꢷꢈꢮꢡꢒꢱꢈꢦꢂꢦ
ꢸꢅꢬꢫꢠꢫꢅꢣꢮꢝꢫꢈꢮꢝꢀꢅꢜꢮꢀꢵꢝꢠꢫꢈꢣꢅꢗꢓꢜꢝꢀꢴꢠꢟꢮꢓꢝꢮꢀꢤꢈꢀꣂꢦꢄꢅꢈꢀꢏꢓꢰꢰꢡꢅꢆꢠꢓꢒꢜꢌꢀꢏꢰꢠꢌꢀꢸꢗꢡꢀꢅꢜꢮꢀꢼꢡꢀꢵꢝꢠꢫꢒꢮꢊꢎꢀW aꢈ#
{ꢍꢒ"ꢉꢍꢀꢀꢁꢁꢅꢌꢀ,ꢑ,ꢌꢀꢧꢪꢎꢀ
ꢁꢨꢿꢃꢀ ꢏꢇꢓꢝꢗꢤꢒꢙꢊꢋꢅꢌꢀꢞꢎꢐꢀꢴꢇꢅꢰꢡꢅꢜꢌꢀꢵꢎꢐꢀꢑꢅꢠꢡꢟꢊꢓꢅꢋꢌꢀꢹꢎꢐꢀꢄꢒꢇꢙꢅꢮꢒꢙꢊꢋꢓꢌꢀ꣐ꢎꢀꢭꢡꢈꢊꢠꢅꢣꢀꢴꢠꢡꢟꢆꢠꢟꢡꢝꢀꢒꢰꢀ
ꢀ
ꢁꢨꢂꢃꢀ ꢴꢓꢠꢋꢒꢙꢊꢋꢓꢌꢀꣀꢎꢐꢀꢴꢠꢝꢰꢅꢜꢓꢅꢋꢌꢀꢶꢎꢐꢀꢏꢇꢓꢝꢗꢤꢒꢙꢊꢋꢅꢌꢀꢞꢎꢐꢀꢛꢡꢝꢆꢫꢌꢀꢍꢎꢐꢀꣀꢅꢺꢒꢮꢇꢓꢜꢊꢋꢅꢌꢀꢍꢎꢐꢀꢔꢝꢤꢤꢌꢀꢛꢎꢀ
ꢹꢎꢀꢹꢀꢵꢟꢣꢠꢓꢜꢟꢆꢣꢝꢅꢡꢀꢸꢗꢡꢀꢴꢠꢟꢮꢈꢀꢒꢰꢀꢥꢡꢒꢠꢒꢜꢀꢞꢡꢅꢜꢊꢰꢝꢡꢀꢥꢡꢒꢆꢝꢊꢊꢝꢊꢀꢓꢜꢀꢴꢆꢫꢓꢰꢰꢀꢚꢅꢊꢝꢊꢎꢀWꢃ aꢈ#ꢃ {ꢍꢒ"ꢉꢍꢀꢃꢅꢅꢄꢌꢀ
ꢏ ꢌꢀꢂꢳꢳꢎꢀ
ꢀ
ꢁꢨꢪꢃꢀ ꢏꢟꢮꢝꢋꢌꢀꢛꢎꢀꢕꢎꢀꢸꢟꢆꢣꢝꢅꢡꢀꢵꢅꢺꢜꢝꢠꢓꢆꢀꢄꢝꢊꢒꢜꢅꢜꢆꢝꢀꢴꢠꢟꢮꢓꢝꢊꢀꢒꢰꢀꢑꢝꢠꢒꢦꢍꢜꢒꢣꢀꢍꢢꢟꢓꢣꢓꢤꢡꢓꢅꢀꢎꢽꢎꢀ
ꢸꢅꢬꢫꢠꢫꢅꢣꢝꢜꢝꢀꢏꢝꢡꢓꢯꢅꢠꢓꢯꢝꢊꢎꢀWꢃ !ꢂꢃ /ꢀꢁꢂꢃ {ꢈꢉꢃꢀꢃꢅꢄꢈꢌꢀꢏꢆꢌꢀꢩ꣄ꢽꢎꢀ
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 21
1
2
3
4
5
6
ꢀ
ꢁꢨꢧꢃꢀ ꢹꢣꢅꢡꢆꢒꢜꢌꢀꢴꢎꢀꢷꢎꢐꢀꢕꢣꢓꢯꢓꢝꢡꢓꢌꢀꢹꢎꢀꢭꢎꢐꢀꢴꢅꢜꢇꢌꢀꢏꢎꢐꢀꢭꢣꢅꢡꢅꢗꢟꢜꢠꢌꢀꢄꢎꢀꢵꢎꢐꢀꢍꢣꢺꢟꢝꢡꢒꢌꢀꣀꢎꢀꢴꢟꢤꢊꢠꢓꢠꢟꢝꢜꢠꢀ
ꢅꢜꢮꢀꢴꢒꢣꢯꢝꢜꢠꢀꢍꢰꢰꢝꢆꢠꢊꢀꢒꢜꢀꢠꢫꢝꢀꢥꢡꢒꢠꢒꢜꢀꢞꢡꢅꢜꢊꢰꢝꢡꢀꢍꢢꢟꢓꢣꢓꢤꢡꢓꢟꢗꢀꢓꢜꢀꢹꢜꢓꢣꢊꢀꢅꢜꢮꢀꢹꢇꢒꢀꢏꢝꢡꢓꢯꢅꢠꢓꢯꢝꢊꢀꢒꢰꢀꢸꢅꢬꢫꢠꢫꢒꢣꢎꢀ
ꢵꢟꢣꢠꢓꢜꢟꢆꢣꢝꢅꢡꢀꢸꢗꢡꢀꢴꢠꢟꢮꢈꢀꢅꢜꢮꢀꢞꢫꢝꢒꢡꢝꢠꢓꢆꢅꢣꢀꢭꢅꢣꢆꢟꢣꢅꢠꢓꢒꢜꢊꢎꢀW aꢈ# {ꢍꢒ"ꢉꢍꢀꢀꢁꢁꢇꢌꢀ'ꢅꢆꢌꢀꢂꢎꢀ
7
ꢀ
ꢁꢨꢽꢃꢀ ꢹꢣꢅꢡꢆꢒꢜꢌꢀꢴꢎꢀꢷꢎꢐꢀꢕꢣꢓꢯꢓꢝꢡꢓꢌꢀꢹꢎꢀꢭꢎꢐꢀꢛꢒꢜꢇꢅꢣꢝꢇꢊꢓꢝꢡꢡꢅꢌꢀꢵꢎꢀꢭꢦꢂꢧꢀꢸꢗꢡꢀꢴꢬꢝꢆꢠꢡꢒꢊꢆꢒꢬꢓꢆꢀꢅꢜꢮꢀꢹꢗꢂꢀ
8
9
ꢴꢠꢟꢮꢈꢀꢒꢰꢀꢠꢫꢝꢀꢼꢜꢠꢡꢅꢗꢒꢣꢝꢆꢟꢣꢅꢡꢀꢥꢡꢒꢠꢒꢜꢦꢞꢡꢅꢜꢊꢰꢝꢡꢀꢓꢜꢀꢹꢜꢓꢣꢊꢀꢒꢰꢀꢴꢅꢣꢓꢆꢈꢣꢅꢣꢮꢝꢫꢈꢮꢝꢀꢅꢜꢮꢀꢪꢦ
ꢷꢈꢮꢡꢒꢱꢈꢜꢅꢬꢫꢠꢫꢅꢣꢝꢜꢝꢦꢂꢦꢭꢅꢡꢤꢅꢣꢮꢝꢫꢈꢮꢝꢎꢀW /ꢀꢁꢂ {ꢈꢉ tꢁꢒ% Ç ꢑꢀꢃꢅꢅꢇꢌꢀꢂꢿꢩꢳꢎꢀ
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ꢀ
ꢁꢨꢨꢃꢀ ꣐ꢫꢟꢒꢌꢀꣀꢎꢀꢭꢎꢀꢸꢗꢡꢀꢒꢰꢀꢍꢜꢅꢗꢓꢜꢒꢜꢝꢊꢎꢀꢥꢅꢡꢠꢀꢩꢀꢦꢀꢕꢦꢂꢳꢀꢅꢜꢮꢀꢭꢦꢂꢧꢀꢸꢗꢡꢀꢴꢠꢟꢮꢈꢀꢒꢰꢀ
ꢞꢅꢟꢠꢒꢗꢝꢡꢓꢇꢅꢠꢓꢒꢜꢀꢓꢜꢀꢴꢆꢫꢓꢰꢰꢀꢚꢅꢊꢝꢊꢎꢀaꢎ+ꢓ wꢁꢌꢈꢓ /ꢀꢁꢂꢀꢃꢅꢅꢅꢌꢀ 'ꢌꢀꢪꢨ꣄ꢎꢀ
ꢁꢨꢩꢃꢀ ꢹꢣꢋꢒꢡꢠꢅꢌꢀꢼꢎꢐꢀꢍꢣꢺꢟꢝꢡꢒꢌꢀꣀꢎꢐꢀꢵꢒꢌꢀꢕꢎꢐꢀꢾꢅꢜꢝꢇꢌꢀꢵꢎꢐꢀꢏꢝꢣꢀꢚꢝꢜꢝꢌꢀꣀꢎꢀꢍꢎꢀꢹꢡꢝꢀꢄꢝꢊꢒꢜꢅꢜꢆꢝꢦꢹꢊꢊꢓꢊꢠꢝꢮꢀ
ꢀ
ꢷꢈꢮꢡꢒꢺꢝꢜꢀꢚꢒꢜꢮꢊꢀꢲꢄꢝꢊꢒꢜꢅꢜꢆꢝꢀꢹꢊꢊꢓꢊꢠꢝꢮꢲ꣑ꢀꢹꢀꢞꢫꢝꢒꢡꢝꢠꢓꢆꢅꢣꢀꢸꢗꢡꢀꢴꢠꢟꢮꢈꢎꢀ/ꢀꢁꢂ tꢀꢋꢌ [ꢁꢍꢍꢀꢀꢁꢁꢂꢌꢀꢐ ꢌꢀ
ꢽꢂꢂꢎꢀ
ꢀ
ꢅꢜꢮꢀꢭꢫꢝꢗꢓꢆꢅꢣꢀꢴꢫꢓꢰꢠꢊꢀꢥꢡꢒꢯꢓꢮꢝꢀꢍꢯꢓꢮꢝꢜꢆꢝꢀꢰꢒꢡꢀꢠꢫꢝꢀꢍꢱꢓꢊꢠꢝꢜꢆꢝꢀꢒꢰꢀꢄꢝꢊꢒꢜꢅꢜꢆꢝꢦꢹꢊꢊꢓꢊꢠꢝꢮꢀꢷꢈꢮꢡꢒꢺꢝꢜꢀꢚꢒꢜꢮꢊ꣑ꢀ
aꢈ# tꢀꢋꢌꢀꢀꢁꢁꢇꢌꢀ ꢅꢑꢌꢀꢪꢨꢩꢧꢎꢀ
ꢀ
ꢁꢨꢳꢃꢀ ꢹꢣꢋꢒꢡꢠꢅꢌꢀꢼꢎꢐꢀꢍꢣꢺꢟꢝꢡꢒꢌꢀꣀꢎꢐꢀꢵꢒꢌꢀꢕꢎꢐꢀꢾꢅꢜꢝꢇꢌꢀꢵꢎꢐꢀꢏꢝꢣꢀꢚꢝꢜꢝꢌꢀꣀꢎꢀꢍꢎꢀꢏꢒꢀꢭꢒꢟꢬꢣꢓꢜꢺꢀꢭꢒꢜꢊꢠꢅꢜꢠꢊꢀ
ꢁꢨꣅꢃꢀ ꢏꢒꢤꢒꢊꢇꢌꢀꢄꢎꢐꢀꢴꢋꢒꢠꢜꢓꢆꢋꢅꢌꢀꢹꢎꢐꢀꢄꢒꢇꢙꢅꢮꢒꢙꢊꢋꢓꢌꢀ꣐ꢎꢐꢀꢏꢇꢓꢝꢗꢤꢒꢙꢊꢋꢅꢌꢀꢞꢎꢐꢀꢛꢅꢙꢓꢜꢝꢆꢋꢓꢌꢀꢄꢎꢀ
ꢴꢠꢅꢤꢓꢣꢓꢠꢈꢀꢒꢰꢀꢸꢦꢁꢕꢡꢠꢫꢒꢦꢷꢈꢮꢡꢒꢱꢈꢜꢅꢬꢫꢠꢫꢈꢣꢗꢝꢠꢫꢈꢣꢝꢜꢝꢃꢵꢝꢠꢫꢈꢣꢅꢗꢓꢜꢝꢊꢀꢅꢜꢮꢀꢞꢫꢝꢓꢡꢀꢞꢅꢟꢠꢒꢗꢝꢡꢊꢎꢀW aꢈ#
{ꢍꢒ"ꢉꢍꢀꢀꢁꢃꢁꢌꢀ,',ꢌꢀꢂ꣄ꢽꢎꢀ
ꢀ
ꢁꢨ꣄ꢃꢀ ꢭꢫꢝꢜꢌꢀ꣐ꢎꢐꢀꢔꢅꢜꢜꢝꢡꢝꢌꢀꢭꢎꢀꢴꢎꢐꢀꢭꢒꢡꢗꢓꢜꢤꢒꢝꢟꢰꢌꢀꢭꢎꢐꢀꢥꢟꢆꢫꢠꢅꢌꢀꢄꢎꢐꢀꢴꢆꢫꢣꢝꢈꢝꢡꢌꢀꢥꢎꢀꢸꢟꢆꢣꢝꢟꢊꢦ
ꢼꢜꢮꢝꢬꢝꢜꢮꢝꢜꢠꢀꢭꢫꢝꢗꢓꢆꢅꢣꢀꢴꢫꢓꢰꢠꢊꢀꢁꢸꢓꢆꢊꢃꢀꢅꢊꢀꢅꢜꢀꢹꢡꢒꢗꢅꢠꢓꢆꢓꢠꢈꢀꢭꢡꢓꢠꢝꢡꢓꢒꢜꢎꢀ/ꢀꢁꢂꢃ wꢁꢄꢃꢀꢀꢁꢁꢂꢌꢀ ꢅꢆꢌꢀꢧꣅꢽꢪꢎꢀ
ꢁꢩꢿꢃꢀ ꢄꢅꢆꢇꢈꢉꢊꢋꢅꢌꢀꢍꢎꢀꢏꢎꢐꢀꢷꢅꢣꢣꢗꢅꢜꢌꢀꢵꢎꢐꢀꢑꢒꢣꢆꢇꢈꢉꢊꢋꢅꢌꢀꢑꢎꢐꢀꢴꢠ꣓ꢬꢜꢓꢝꢙꢊꢋꢓꢌꢀꢞꢎꢀꢵꢎꢀꢕꢜꢀꢠꢫꢝꢀ
ꢀ
ꢷꢅꢡꢗꢒꢜꢓꢆꢀꢕꢊꢆꢓꢣꢣꢅꢠꢒꢡꢀꢵꢒꢮꢝꢣꢀꢒꢰꢀꢍꢣꢝꢆꢠꢡꢒꢜꢀꢏꢝꢣꢒꢆꢅꢣꢓꢇꢅꢠꢓꢒꢜꢀꢁꢷꢒꢗꢝꢮꢃꢀꢼꢜꢮꢝꢱꢀꢅꢜꢮꢀꢼꢠꢊꢀꢹꢬꢬꢣꢓꢆꢅꢠꢓꢒꢜꢀꢠꢒꢀ
ꢷꢝꢠꢝꢡꢒꢅꢠꢒꢗꢓꢆꢀꢥꢓꢦꢍꢣꢝꢆꢠꢡꢒꢜꢀꢴꢈꢊꢠꢝꢗꢊꢎꢀ{ꢋꢂꢂꢁꢍꢒꢋꢀꢀꢁꢃꢁꢌꢀꢑꢌꢀꢂꢽꣅꢨꢎꢀ
ꢀ
ꢼꢜꢠꢝꢡꢅꢆꢠꢓꢒꢜꢊꢀꢄꢝꢰꢣꢝꢆꢠꢝꢮꢀꢓꢜꢀꢹꢡꢒꢗꢅꢠꢓꢆꢀꢭꢫꢅꢡꢅꢆꢠꢝꢡꢀꢒꢰꢀꢥꢓꢦꢍꢣꢝꢆꢠꢡꢒꢜꢀꢴꢈꢊꢠꢝꢗꢎꢀWꢃ /ꢀꢁꢂꢃ Lꢓ0ꢃ /ꢈꢂꢊ"ꢍꢃ {ꢉꢇꢃꢀ
ꢃꢅꢅꢈꢌꢀ ꢌꢀꢳꢿꢎꢀ
ꢁꢩꢂꢃꢀ ꢑꢡꢈꢺꢒꢙꢊꢋꢓꢌꢀꢞꢎꢀꢵꢎꢀꢭꢡꢈꢊꢠꢒꢣꢣꢒꢺꢡꢅꢬꢫꢓꢆꢀꢴꢠꢟꢮꢓꢝꢊꢀꢒꢰꢀꢼꢜꢠꢝꢡꢦꢀꢅꢜꢮꢀꢼꢜꢠꢡꢅꢗꢒꢣꢝꢆꢟꢣꢅꢡꢀ
ꢀ
ꢁꢩꢪꢃꢀ ꢚꢝꢆꢋꢝꢌꢀꢹꢎꢀꢏꢎꢀꢏꢝꢜꢊꢓꢠꢈꢦꣁꢟꢜꢆꢠꢓꢒꢜꢅꢣꢀꢞꢫꢝꢡꢗꢒꢆꢫꢝꢗꢓꢊꢠꢡꢈꢀꢎꢧꢎꢀꢞꢫꢝꢀꢄꢒꢣꢝꢀꢒꢰꢀꢍꢱꢅꢆꢠꢀꢍꢱꢆꢫꢅꢜꢺꢝꢎꢀ
Wꢃ /ꢀꢁꢂꢃ tꢀꢋꢌꢃꢀꢃꢅꢅꢈꢌꢀ,ꢏꢌꢀꢨꢩꢽꣅꢎꢀ
ꢁꢩꢧꢃꢀ ꢶꢝꢝꢌꢀꢭꢎꢀꢞꢎꢐꢀꢾꢅꢜꢺꢌꢀꢔꢎꢀꢞꢎꢐꢀꢥꢅꢡꢡꢌꢀꢄꢎꢀꢛꢎꢀꢏꢝꢯꢝꢣꢒꢬꢗꢝꢜꢠꢀꢒꢰꢀꢠꢫꢝꢀꢭꢒꢣꢣꢝꢦꢴꢅꢣꢯꢝꢠꢠꢓꢀꢭꢒꢡꢡꢝꢣꢅꢠꢓꢒꢜꢦ
ꢍꢜꢝꢡꢺꢈꢀꣁꢒꢡꢗꢟꢣꢅꢀꢓꢜꢠꢒꢀꢅꢀꣁꢟꢜꢆꢠꢓꢒꢜꢅꢣꢀꢒꢰꢀꢠꢫꢝꢀꢍꢣꢝꢆꢠꢡꢒꢜꢦꢏꢝꢜꢊꢓꢠꢈꢎꢀtꢀꢋꢌꢃ wꢁꢄꢃ .ꢀꢃꢅꢆꢆꢌꢀ 'ꢌꢀꢳꣅꢨꢎꢀ
ꢁꢩꢽꢃꢀ ꢛꢅꢟꢊꢊꢓꢅꢜꢀꢿ꣄ꢌꢀꢄꢝꢯꢓꢊꢓꢒꢜꢀꢹꢎꢿꢪꢌꢀꢵꢎꢀꣀꢎꢀꣁꢡꢓꢊꢆꢫꢌꢀꢛꢎꢀꢔꢎꢀꢞꢡꢟꢆꢋꢊꢌꢀꢷꢎꢀꢚꢎꢀꢴꢆꢫꢣꢝꢺꢝꢣꢌꢀꢛꢎꢀꢍꢎꢀ
ꢀ
ꢀ
ꢴꢆꢟꢊꢝꢡꢓꢅꢌꢀꢵꢎꢀꢹꢎꢀꢄꢒꢤꢤꢌꢀꣀꢎꢀꢄꢎꢀꢭꢫꢝꢝꢊꢝꢗꢅꢜꢌꢀꢛꢎꢀꢴꢆꢅꢣꢗꢅꢜꢓꢌꢀ꣇ꢎꢀꢚꢅꢡꢒꢜꢝꢌꢀꢛꢎꢀꢹꢎꢀꢥꢝꢠꢝꢡꢊꢊꢒꢜꢌꢀꢷꢎꢀꢸꢅꢋꢅꢠꢊꢟ꣆ꢓꢌꢀꣂꢎꢀ
ꢶꢓꢌꢀꢵꢎꢀꢭꢅꢡꢓꢆꢅꢠꢒꢌꢀꢹꢎꢀꢵꢅꢡꢝꢜꢓꢆꢫꢌꢀꣀꢎꢀꢚꢣꢒꢓꢜꢒꢌꢀꢚꢎꢀꢛꢎꢀꣀꢅꢜꢝꢊꢋꢒꢌꢀꢄꢎꢀꢛꢒꢗꢬꢝꢡꢠꢊꢌꢀꢚꢎꢀꢵꢝꢜꢜꢟꢆꢆꢓꢌꢀꢷꢎꢀꢥꢎꢀꢷꢡꢅꢠꢆꢫꢓꢅꢜꢌꢀ
ꣀꢎꢀ꣇ꢎꢀꢕꢡꢠꢓꢇꢌꢀꢹꢎꢀꣁꢎꢀꢼꢇꢗꢅꢈꢣꢒꢯꢌꢀꣀꢎꢀꢶꢎꢀꢴꢒꢜꢜꢝꢜꢤꢝꢡꢺꢌꢀꢏꢎꢀꢔꢓꢣꢣꢓꢅꢗꢊꢦꢾꢒꢟꢜꢺꢌꢀꣁꢎꢀꢏꢓꢜꢺꢌꢀꣁꢎꢀꢶꢓꢬꢬꢅꢡꢓꢜꢓꢌꢀꣁꢎꢀꢍꢺꢓꢮꢓꢌꢀꣀꢎꢀ
ꢛꢒꢓꢜꢺꢊꢌꢀꢚꢎꢀꢥꢝꢜꢺꢌꢀꢹꢎꢀꢥꢝꢠꢡꢒꢜꢝꢌꢀꢞꢎꢀꢷꢝꢜꢮꢝꢡꢊꢒꢜꢌꢀꢏꢎꢀꢄꢅꢜꢅꢊꢓꢜꢺꢫꢝꢌꢀ꣇ꢎꢀꢛꢎꢀ꣐ꢅꢋꢡꢇꢝꢙꢊꢋꢓꢌꢀꣀꢎꢀꢛꢅꢒꢌꢀꢸꢎꢀꢄꢝꢺꢅꢌꢀꢛꢎꢀ
꣐ꢫꢝꢜꢺꢌꢀꢔꢎꢀꢶꢓꢅꢜꢺꢌꢀꢵꢎꢀꢷꢅꢮꢅꢌꢀꢵꢎꢀꢍꢫꢅꢡꢅꢌꢀꢑꢎꢀꢞꢒꢈꢒꢠꢅꢌꢀꢄꢎꢀꣁꢟꢋꢟꢮꢅꢌꢀꣀꢎꢀꢷꢅꢊꢝꢺꢅꢙꢅꢌꢀꢵꢎꢀꢼꢊꢫꢓꢮꢅꢌꢀꢞꢎꢀꢸꢅꢋꢅ꣆ꢓꢗꢅꢌꢀ
ꢾꢎꢀꢷꢒꢜꢮꢅꢌꢀꢕꢎꢀꢑꢓꢠꢅꢒꢌꢀꢷꢎꢀꢸꢅꢋꢅꢓꢌꢀꢞꢎꢀ꣇ꢡꢝꢯꢝꢜꢌꢀꢑꢎꢀꢞꢫꢡꢒꢊꢊꢝꢣꢣꢌꢀꣀꢎꢀꢹꢎꢀꢵꢒꢜꢠꢺꢒꢗꢝꢡꢈꢌꢀꣀꢡꢎꢌꢀꣀꢎꢀꢍꢎꢀꢥꢝꢡꢅꢣꢠꢅꢌꢀꣁꢎꢀ
ꢕꢺꢣꢓꢅꢡꢒꢌꢀꢵꢎꢀꢚꢝꢅꢡꢬꢅꢡꢋꢌꢀꣀꢎꢀꣀꢎꢀꢷꢝꢈꢮꢌꢀꢍꢎꢀꢚꢡꢒꢠꢫꢝꢡꢊꢌꢀꢑꢎꢀꢸꢎꢀꢑꢟꢮꢓꢜꢌꢀ꣇ꢎꢀꢸꢎꢀꢴꢠꢅꢡꢒꢯꢝꢡꢒꢯꢌꢀꢞꢎꢀꢑꢝꢓꢠꢫꢌꢀꢄꢎꢀꢑꢒꢤꢅꢈꢅꢊꢫꢓꢌꢀ
ꣀꢎꢀꢸꢒꢡꢗꢅꢜꢮꢌꢀꢑꢎꢀꢄꢅꢺꢫꢅꢯꢅꢆꢫꢅꢡꢓꢌꢀꢹꢎꢀꢄꢝꢜꢮꢝꢣꢣꢌꢀꣀꢎꢀꢭꢎꢀꢚꢟꢡꢅꢜꢠꢌꢀꢴꢎꢀꢴꢎꢀꢼꢈꢝꢜꢺꢅꢡꢌꢀꣀꢎꢀꢞꢒꢗꢅꢊꢓꢌꢀꢵꢎꢀꢭꢒꢊꢊꢓꢌꢀꣀꢎꢀꢵꢎꢀ
ꢵꢓꢣꢣꢅꢗꢌꢀꢵꢎꢀꢑꢣꢝꢜꢝꢌꢀꢭꢎꢀꢹꢮꢅꢗꢒꢌꢀꢄꢎꢀꢭꢅꢗꢗꢓꢌꢀꣀꢎꢀꢔꢎꢀꢕꢆꢫꢠꢝꢡꢊꢋꢓꢌꢀꢄꢎꢀꢶꢎꢀꢵꢅꢡꢠꢓꢜꢌꢀꢑꢎꢀꢵꢒꢡꢒꢋꢟꢗꢅꢌꢀꢕꢎꢀꣁꢅꢡꢋꢅꢊꢌꢀꣀꢎꢀ
ꢚꢎꢀꣁꢒꢡꢝꢊꢗꢅꢜꢌꢀꢅꢜꢮꢀꢏꢎꢀꣀꢎꢀꣁꢒꢱꢌꢀꢛꢅꢟꢊꢊꢓꢅꢜꢌꢀꢼꢜꢆꢎꢌꢀꢔꢅꢣꢣꢓꢜꢺꢰꢒꢡꢮꢀꢭꢞꢌꢀꢪꢿꢂꢩꢎꢀ
ꢀ
ꢁꢩꢨꢃꢀ ꢾꢅꢜꢅꢓꢌꢀꢞꢎꢐꢀꢞꢝꢙꢌꢀꢏꢎꢀꢥꢎꢐꢀꢷꢅꢜꢮꢈꢌꢀꢸꢎꢀꢭꢎꢀꢹꢀꢸꢝꢙꢀꢷꢈꢤꢡꢓꢮꢀꢍꢱꢆꢫꢅꢜꢺꢝꢦꢭꢒꢡꢡꢝꢣꢅꢠꢓꢒꢜꢀꣁꢟꢜꢆꢠꢓꢒꢜꢅꢣꢀ
꣒ꢊꢓꢜꢺꢀꢠꢫꢝꢀꢭꢒꢟꢣꢒꢗꢤꢦꢹꢠꢠꢝꢜꢟꢅꢠꢓꢜꢺꢀꢵꢝꢠꢫꢒꢮꢀꢁꢭꢅꢗꢦꢚꢧꢣꢈꢬꢃꢎꢀ/ꢀꢁꢂ tꢀꢋꢌ [ꢁꢍꢍꢀꢀꢁꢁꢇꢌꢀ , ꢌꢀꢨꢂꢎꢀ
ꢁꢩꢩꢃꢀ ꣐ꢅꢫꢒꢌꢀꢾꢎꢐꢀꢞꢡꢟꢫꢣꢅꢡꢌꢀꢏꢎꢀꢛꢎꢀꢞꢫꢝꢀꢵꢿꢩꢀꢴꢟꢓꢠꢝꢀꢒꢰꢀꢏꢝꢜꢊꢓꢠꢈꢀꣁꢟꢜꢆꢠꢓꢒꢜꢅꢣꢊꢀꢰꢒꢡꢀꢵꢅꢓꢜꢀꢛꢡꢒꢟꢬꢀ
ꢀ
ꢞꢫꢝꢡꢗꢒꢆꢫꢝꢗꢓꢊꢠꢡꢈꢌꢀꢞꢫꢝꢡꢗꢒꢆꢫꢝꢗꢓꢆꢅꢣꢀꢑꢓꢜꢝꢠꢓꢆꢊꢌꢀꢸꢒꢜꢆꢒꢯꢅꢣꢝꢜꢠꢀꢼꢜꢠꢝꢡꢅꢆꢠꢓꢒꢜꢊꢌꢀꢍꢱꢆꢓꢠꢝꢮꢀꢴꢠꢅꢠꢝꢊꢌꢀꢅꢜꢮꢀ
ACS Paragon Plus Environment

Page 21 of 21
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
ꢞꢡꢅꢜꢊꢓꢠꢓꢒꢜꢀꢍꢣꢝꢗꢝꢜꢠꢊꢻꢀꢞꢙꢒꢀꢸꢝꢙꢀꣁꢟꢜꢆꢠꢓꢒꢜꢅꢣꢊꢀꢅꢜꢮꢀꢴꢈꢊꢠꢝꢗꢅꢠꢓꢆꢀꢞꢝꢊꢠꢓꢜꢺꢀꢒꢰꢀꣁꢒꢟꢡꢀꢵꢿꢩꢦꢭꢣꢅꢊꢊꢀ
ꣁꢟꢜꢆꢠꢓꢒꢜꢅꢣꢊꢀꢅꢜꢮꢀꢂꢪꢀꢕꢠꢫꢝꢡꢀꣁꢟꢜꢆꢠꢓꢒꢜꢅꢣꢊꢎꢀÇꢀꢁꢈꢒꢃ /ꢀꢁꢂꢃ !ꢉꢉꢃꢀꢀꢁꢁ ꢌꢀ ꢑꢅꢌꢀꢪꢂꢨꢎꢀ
ꢀ
ꢁꢩꢳꢃꢀ ꢵꢅꢡꢠꢈꢜꢓꢅꢋꢌꢀꢹꢎꢐꢀꢵꢅ꣆ꢝꢡꢇꢌꢀꢼꢎꢐꢀꣁꢓꢣꢅꢡꢒꢙꢊꢋꢓꢌꢀꢹꢎꢀꢥꢝꢆꢟꢣꢓꢅꢡꢓꢠꢓꢝꢊꢀꢒꢰꢀ꣋ꢟꢅꢊꢓꢦꢹꢡꢒꢗꢅꢠꢓꢆꢀꢷꢈꢮꢡꢒꢺꢝꢜꢀ
ꢚꢒꢜꢮꢓꢜꢺꢎꢀw{/ !ꢔꢄꢃꢀꢀꢁꢃꢀꢌꢀꢑꢌꢀꣅꢂꢧꢨꢎꢀ
ꢁꢩꣅꢃꢀ ꢵꢅꢊꢟꢗꢓꢅꢜꢌꢀꢍꢎꢐꢀꢸꢒꢙꢡꢒꢒꢇꢓꢌꢀꢹꢎꢀꢭꢒꢗꢬꢟꢠꢅꢠꢓꢒꢜꢅꢣꢀꢼꢜꢯꢝꢊꢠꢓꢺꢅꢠꢓꢒꢜꢀꢒꢜꢀꢠꢫꢝꢀꢼꢜꢠꢡꢅꢗꢒꢣꢝꢆꢟꢣꢅꢡꢀ
ꢀ
ꢄꢝꢊꢒꢜꢅꢜꢆꢝꢦꢼꢜꢫꢓꢤꢓꢠꢝꢮꢀꢷꢈꢮꢡꢒꢺꢝꢜꢀꢚꢒꢜꢮꢓꢜꢺꢻꢀꢹꢀꢸꢝꢙꢀꢞꢈꢬꢝꢀꢒꢰꢀꢼꢜꢠꢝꢡꢅꢆꢠꢓꢒꢜꢀ꣇ꢝꢡꢊꢟꢊꢀꢠꢫꢝꢀꢄꢅꢫꢤꢀꢵꢒꢮꢝꢣꢎꢀ
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Çꢀꢁꢈꢒꢃ /ꢀꢁꢂꢃ !ꢉꢉꢃꢀꢀꢁꢃꢂꢌꢀ ꢐꢎꢀ
ꢀ
ꢁꢩ꣄ꢃꢀ ꢶꢓꢜꢌꢀꣂꢎꢀꢷꢎꢐꢀ꣐ꢫꢅꢜꢺꢌꢀꢷꢎꢀꢾꢎꢐꢀꣀꢓꢅꢜꢺꢌꢀꣂꢎꢐꢀꢔꢟꢌꢀꢔꢎꢐꢀꢵꢒꢌꢀꢾꢎꢀꢄꢎꢀꢞꢫꢝꢀꢕꢡꢓꢺꢓꢜꢀꢒꢰꢀꢠꢫꢝꢀꢸꢒꢜꢦ
ꢹꢮꢮꢓꢠꢓꢯꢓꢠꢈꢀꢓꢜꢀꢄꢝꢊꢒꢜꢅꢜꢆꢝꢦꢹꢊꢊꢓꢊꢠꢝꢮꢀꢷꢈꢮꢡꢒꢺꢝꢜꢀꢚꢒꢜꢮꢀꢴꢈꢊꢠꢝꢗꢊꢎꢀWꢃ tꢀꢋꢌꢃ /ꢀꢁꢂꢃ !ꢃ.ꢀꢀꢁꢃ ꢌꢀ ꢑ ꢌꢀꣅꢨꢧꢨꢎꢀ
ꢁꢳꢿꢃꢀ ꢭꢣꢅꢡꢋꢌꢀꢴꢎꢐꢀꢴꢝꢺꢅꢣꢣꢌꢀꢵꢎꢀꢏꢎꢐꢀꢥꢓꢆꢋꢅꢡꢮꢌꢀꢭꢎꢀꣀꢎꢐꢀꢷꢅꢊꢜꢓꢬꢌꢀꢥꢎꢀꣀꢎꢐꢀꢥꢡꢒꢤꢝꢡꢠꢌꢀꢵꢎꢀꣀꢎꢐꢀꢄꢝꢰꢊꢒꢜꢌꢀꢑꢎꢐꢀ
ꢥꢅꢈꢜꢝꢌꢀꢵꢎꢀꢭꢎꢀùꢃ Yꢒꢋꢌꢍꢎ##ꢈ+ꢒꢃꢀꢀꢁꢁꢂꢌꢀꢑꢑꢅꢌꢀꢨꢩꢳꢎꢀ
ꢁꢳꢂꢃꢀ ꢥꢝꢡꢮꢝꢙꢌꢀꣀꢎꢀꢥꢎꢐꢀꢚꢟꢡꢋꢝꢌꢀꢑꢎꢐꢀꢍꢡꢜꢇꢝꢡꢫꢒꢰꢌꢀꢵꢎꢀꢛꢝꢜꢝꢡꢅꢣꢓꢇꢝꢮꢀꢛꢡꢅꢮꢓꢝꢜꢠꢀꢹꢬꢬꢡꢒꢱꢓꢗꢅꢠꢓꢒꢜꢀ
ꢵꢅꢮꢝꢀꢴꢓꢗꢬꢣꢝꢎꢀtꢀꢋꢌꢃ wꢁꢄꢃ [ꢁꢍꢍꢃꢀꢃꢅꢅꢄꢌꢀ''ꢌꢀꢧꣅꢩꢨꢎꢀ
ꢁꢳꢪꢃꢀ ꢞꢋꢅꢠꢆꢫꢝꢜꢋꢒꢌꢀꢹꢎꢐꢀꢴꢆꢫꢝꢰꢰꢣꢝꢡꢌꢀꢵꢎꢀꢹꢆꢆꢟꢡꢅꢠꢝꢀꢵꢒꢣꢝꢆꢟꢣꢅꢡꢀ꣇ꢅꢜꢀꢏꢝꢡꢀꢔꢅꢅꢣꢊꢀꢼꢜꢠꢝꢡꢅꢆꢠꢓꢒꢜꢊꢀ
ꢰꢡꢒꢗꢀꢛꢡꢒꢟꢜꢮꢦꢴꢠꢅꢠꢝꢀꢍꢣꢝꢆꢠꢡꢒꢜꢀꢏꢝꢜꢊꢓꢠꢈꢀꢅꢜꢮꢀꣁꢡꢝꢝꢦꢹꢠꢒꢗꢀꢄꢝꢰꢝꢡꢝꢜꢆꢝꢀꢏꢅꢠꢅꢎꢀtꢀꢋꢌꢃ wꢁꢄꢃ [ꢁꢍꢍꢃꢀꢀꢁꢁꢅꢌꢀ ꢅꢑꢎꢀ
ꢁꢳꢧꢃꢀ ꣂꢓꢅꢌꢀꢴꢎꢀꢷꢎꢐꢀꢛꢅꢜꢌꢀꢶꢎꢐꢀꢔꢅꢜꢺꢌꢀꢑꢎꢀꢷꢎꢐꢀꢶꢓꢌꢀ꣐ꢎꢐꢀꢵꢅꢌꢀꢏꢎꢀꢔꢎꢀꢭꢒꢬꢬꢝꢡꢦꢭꢅꢠꢅꢣꢈꢇꢝꢮꢀꢷꢈꢮꢡꢒꢱꢈꢣꢅꢠꢓꢒꢜꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢒꢰꢀꢁꢷꢝꢠꢝꢡꢒꢃꢹꢡꢈꢣꢀꢷꢅꢣꢓꢮꢝꢊꢀꢟꢜꢮꢝꢡꢀꢵꢓꢣꢮꢀꢭꢒꢜꢮꢓꢠꢓꢒꢜꢊꢎꢀWꢃ !ꢂꢃ /ꢀꢁꢂꢃ {ꢈꢉꢃꢀꢀꢁꢃꢄꢌꢀ ꢏꢌꢀꢂꢧꢽ꣄ꢧꢎꢀ
ACS Paragon Plus Environment