Supplemental Information

Substitution Reactions on Iodine and Bromine – Mechanisms

for Facile Halogenations of Heterocycles.
Leah L. Donham1 and Scott Gronert1,2*
1
Department of Chemistry, Virginia Commonwealth University, 1001 W Main Street, Richmond, VA 23284 USA
Department of Chemistry and Biochemistry, University of Wisconsin – Milwaukee, 3210 N. Cramer St.,
2

Milwaukee, WI 53211 USA

sgronert@uwm.edu

Table of Contents
I. Full Citation for References 30-32 ......................................................................................... 2
II. Spectra..................................................................................................................................... 3
III. Kinetic Data ....................................................................................................................... 15
IV. Energetic Data .................................................................................................................... 16
a. Reaction Profiles ................................................................................................................ 16
b. Electron Affinity Data........................................................................................................ 17
c. Hypoiodite Formation ........................................................................................................ 17
d. Computed Data .................................................................................................................. 18
i. Reactants ........................................................................................................................ 18
ii. Products ...................................................................................................................... 20
iii. Transition States and Post-Transition States .............................................................. 26
iv. 3-Cyanopyridine Data................................................................................................. 31
v. 2-Thiazolide Ring Opening Data ................................................................................ 35
vi. Hypoiodite Data .......................................................................................................... 36
e. Transition State Geometries ............................................................................................... 39

S1
 I. Full Citation for References 30-32
30. M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, J. J. A.
Montgomery, T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S. Iyengar, J. Tomasi, V.
Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A. Petersson, H. Nakatsuji, M. Hada,
M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H.
Nakai, M. Klene, X. Li, J.E. Knox, H.P. Hratchian, J.B. Cross, C. Adamo, J. Jaramillo, R.
Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y.
Ayala, K. Morokuma, G.A. Voth, P. Salvador, J.J. Dannenberg, V.G. Zakrzewski, S. Dapprich,
A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B.
Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J. Cioslowski, B.B. Stefanov, G. Liu, A.
Liashenko, P. Piskorz, I. Komaromi, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y.
Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M.W. Wong, C.
Gonzalez, J.A. Pople, Gaussian 03, in, Gaussian, Inc., Pittsburgh, PA, 2003.
31. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G.
Scalmani, V. Barone, G. A. Petersson, H. Nakatsuji, X. Li, M. Caricato, A. Marenich, J. Bloino,
B. G. Janesko, R. Gomperts, B. Mennucci, H. P. Hratchian, J. V. Ortiz, A. F. Izmaylov, J. L.
Sonnenberg, D. Williams-Young, F. Ding, F. Lipparini, F. Egidi, J. Goings, B. Peng, A. Petrone,
T. Henderson, D. Ranasinghe, V. G. Zakrzewski, J. Gao, N. Rega, G. Zheng, W. Liang, M.
Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O.
Kitao, H. Nakai, T. Vreven, K. Throssell, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M.
Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, T. Keith, R. Kobayashi, J.
Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, J. M.
Millam, M. Klene, C. Adamo, R. Cammi, J. W. Ochterski, R. L. Martin, K. Morokuma, O.
Farkas, J. B. Foresman, and D. J. Fox, Gaussian 09 Revision A02; Gaussian Inc, Wallingford CT
(2009).
32. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J.
R.; Scalmani, G.; Barone, V.; Petersson, G. A.; Nakatsuji, H.; Li, X.; Caricato, M.; Marenich, A.
V.; Bloino, J.; Janesko, B. G.; Gomperts, R.; Mennucci, B.; Hratchian, H. P.; Ortiz, J. V.;
Izmaylov, A. F.; Sonnenberg, J. L.; Williams-Young, D.; Ding, F.; Lippa-rini, F.; Egidi, F.;
Goings, J.; Peng, B.; Petrone, A.; Hen-derson, T.; Ranasinghe, D.; Zakrzewski, V. G.; Gao, J.;
Re-ga, N.; Zheng, G.; Liang, W.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Throssell, K.;
Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M. J.; Heyd, J. J.; Brothers, E. N.;
Kudin, K. N.; Staroverov, V. N.; Keith, T. A.; Kobayashi, R.; Normand, J.; Raghavachari, K.;
Rendell, A. P.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Millam, J. M.; Klene, M.;
Adamo, C.; Cammi, R.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Farkas, O.; Foresman, J.
B.; Fox, D. J. Gaussian 16 Revision B01; Gaussian Inc, Wallingford CT (2016).

S2
 II. Spectra

Figure S1. The reaction of 2-thiazolide with pentafluoroiodobenzene. The 2-thiazolide anion
was formed by CID on carboxylate of 2-thiazole carboxylic acid. The 2-thiazolide was then
isolated and allowed to react with the pentafluoroiodobenzene. In this reaction, the products
formed were iodide (m/z 127), the pentafluorophenyl anion (m/z 167) and the anionic product
from the SNAr(F) (m/z 358, charge placed in most likely position).

S3
Figure S2. The reaction of 2-thiazolide with bromopentafluorobenzene. The 2-thiazolide anion
was formed by CID on carboxylate of 2-thiazole carboxylic acid. The 2-thiazolide was then
isolated and allowed to react with the bromopentafluorobenzene. In this reaction, the products
formed were the bromide (m/z 79/81), and the pentafluorophenyl anion (m/z 167).

S4
Figure S3. The reaction of 2-thiazolide with 1-iodoheptafluoropropane. The 2-thiazolide anion
was formed by CID on carboxylate of 2-thiazole carboxylic acid. The 2-thiazolide was then
isolated and allowed to react with 1-iodoheptafluoropropane. In this reaction, the products
formed were the iodide (m/z 127), the heptafluoropropyl anion (m/z 169), the deprotonated 2-
iodothiazole (m/z 209, charge placed on most likely location), and the product from the
sequential substitution/elimination of -IF from the iodoheptafluoropropane (m/z 230, proposed
structure above).

S5
Figure S4. The reaction of 2-thiazolide with 2-iodoheptafluoropropane. The 2-thiazolide anion
was formed by CID on carboxylate of 2-thiazole carboxylic acid. The 2-thiazolide was then
isolated and allowed to react with 2-iodoheptafluoropropane. In this reaction, the products
formed were the heptafluoropropyl anion (m/z 169), and the product from the sequential
substitution/elimination of -IF from the iodoheptafluoropropane (m/z 230, proposed structure
above).

S6
Figure S5. The reaction of 5-thiazolide with pentafluoroiodobenzene. The 5-thiazolide anion
was formed by CID on carboxylate of 5-thiazole carboxylic acid. The 5-thiazolide was then
isolated and allowed to react with pentafluoroiodobenzene. In this reaction, the products formed
were the iodide (m/z 127), the pentafluorophenyl anion (m/z 167), and the anionic product from
the SNAr(F) reaction (m/z 358, with charge placed on most likely location).

S7
Figure S6. The reaction of 5-thiazolide with bromopentafluorobenzene. The 5-thiazolide anion
was formed by CID on carboxylate of 5-thiazole carboxylic acid. The 5-thiazolide was then
isolated and allowed to react with bromopentafluorobenzene. In this reaction, the products
formed were the bromide (m/z 79/81), the pentafluorophenyl anion (m/z 167), and the anionic
product from the SNAr(F) reaction (m/z 310/312, with charge placed in most likely location).

S8
Figure S7. The reaction of 5-thiazolide with 1-iodoheptafluoropropane. The 5-thiazolide anion
was formed by CID on carboxylate of 5-thiazole carboxylic acid. The 5-thiazolide was then
isolated and allowed to react with 1-iodoheptafluoropropane. In this reaction, the products
formed were iodide (m/z 127), the heptafluoropropyl anion (m/z 169), the anionic 5-iodothiazole
(m/z 210, with the charge located in the most likely location), and the product from the
sequential substitution/elimination of -IF from the iodoheptafluoropropane (m/z 230, proposed
structure above).

S9
Figure S8. The reaction of 5-thiazolide with 2-iodoheptafluoropropane. The 5-thiazolide anion
was formed by CID on carboxylate of 5-thiazole carboxylic acid. The 5-thiazolide was then
isolated and allowed to react with 2-iodoheptafluoropropane. In this reaction, the products
formed were the heptafluoropropyl anion (m/z 169), and the product from the sequential
substitution/elimination of -IF from the iodoheptafluoropropane (m/z 230, proposed structure
above).

S10
Figure S9. The reaction of 5-isothiazolide with pentafluoroiodobenzene. The 5-isothiazolide
anion was formed by CID on carboxylate of 5-isothiazole carboxylic acid. The 5-isothiazolide
was then isolated and allowed to react with pentafluoroiodobenzene. In this reaction, the
products formed were iodide (m/z 127), the pentafluorophenyl anion (m/z 167), and the anionic
product from the SNAr(F) reaction (m/z 358, with the charge placed on the most likely location).

S11
Figure S10. The reaction of 5-isothiazolide with bromopentafluorobenzene. The 5-isothiazolide
anion was formed by CID on carboxylate of 5-isothiazole carboxylic acid. The 5-isothiazolide
was then isolated and allowed to react with bromopentafluorobenzene. In this reaction, the
products formed were bromide (m/z 79/81), the pentafluorophenyl anion (m/z 167), and the
anionic product from the SNAr(F) reaction (m/z 310/312, with the charge placed on the most
likely location).

S12
Figure S11. The reaction of 5-isothiazolide with 1-iodoheptafluoropropane. The 5-isothiazolide
anion was formed by CID on carboxylate of 5-isothiazole carboxylic acid. The 5-isothiazolide
was then isolated and allowed to react with 1-iodoheptafluoropropane. In this reaction, the
products formed were iodide (m/z 127), the heptafluoropropyl anion (m/z 169), the anionic 5-
iodothiazole (m/z 210, with charge placed in most likely location), and the product from the
sequential substitution/elimination of -IF from the iodoheptafluoropropane (m/z 230, proposed
structure above).

S13
Figure S12. The reaction of 5-isothiazolide with 2-iodoheptafluoropropane. The 5-isothiazolide
anion was formed by CID on carboxylate of 5-isothiazole carboxylic acid. The 5-isothiazolide
was then isolated and allowed to react with 2-iodoheptafluoropropane. In this reaction, the
products formed were the heptafluoropropyl anion (m/z 169), and the product from the
sequential substitution/elimination of -IF from the iodoheptafluoropropane (m/z 230, proposed
structure above).

S14
 III. Kinetic Data

Substrate Nucleophile ka Std deva Efficiency (%)b % Halogenation

Pentafluoroiodobenzene 2-thiazolide 16.8 1 125 96
5-thiazolide 22.3 0.8 165 68
5-isothiazolide 21.8 1 165 83

Bromopentafluorobenzene 2-thiazolide 17.0 2 141 84

5-thiazolide 15.1 0.9 125 74
5-isothiazolide 16.3 0.9 135 80

Heptafluoro-1-iodopropane 2-thiazolide 5.8 0.4 45 84

5-thiazolide 6.0 0.2 45 89
5-isothiazolide 6.5 0.3 50 77

Heptafluoro-2-iodopropane 2-thiazolide 4.0 0.3 30 99

5-thiazolide 6.5 0.2 50 99
5-isothiazolide 6.9 0.4 55 90
a
Units 10-10 cc/mol/sec.
b
Values above 100% are likely a result of breakdowns in the assumptions in the ADO model.

Table S1. Kinetic data for the reactions. Efficiency calculated using k/kADO (Su, T.; Bowers, M.
T. Classical Ion-Molecule Collision Theory. In Gas Phase Ion Chemistry; Bowers, M. T., Ed.;
Academic Press: New York, 1979; Vol. 1, pp 83–118). Percent halogenation is fraction of all
products formed via an SN2@X pathway.

Reagent dipole polarizability

(debye) (Å3)
bromopentafluorobenzene 0.80 13.26
iodopentafluorobenzene 1.08 15.45
1-iodoheptafluorobenzene 1.44 11.62
2-iodoheptafluorobenzene 1.42 11.40

Table S2. Dipole and polarizability data used in ADO calculation. Dipole moments taken from
calculations at the MP2/6-31+G* level. Polarizabilities derived from refractive index data.

S15
 IV. Energetic Data

a. Reaction Profiles

-5

-10

-15
ΔE (kcal/mol)

-20

-25

-30

-35

-40

-45

-50

Figure S13. Energy profile for reaction of 2-thiazolide with 2-bromoheptafluoropropane. Pre-
and post-transition state complexes are not shown.

S16
 b. Electron Affinity Data

Electron
Molecule Affinities (eV)
2-thiazolyl radical 2.75
5-thiazolyl radical 2.41
5-isothiazolyl radical 2.49

Bromopentafluorobenzene 1.15a
Pentafluoroiodobenzene 1.40
Heptafluoro-1-iodopropane 1.56
Heptafluoro-2-iodopropane 1.82

Table S3. Electron affinity data for nucleophiles and neutral reagents used in this study. Values
calculated at the M062X/QZVP level.
a
Experimental value taken from NIST Chemistry Webbook (webbook.nist.gov/chemistry/,
accessed May 25, 2018).

c. Hypoiodite Formation

Enthalpy
Molecule (hartree)
CF3CF2CF2CF2I -1348.74657
CF3CF2CF2CF2– -1051.131974
t-C4H9OI -530.541192
t-C4H9O– -232.935902

t-BuO– + CF3CF2CF2CF2I t-BuOI + CF3CF2CF2CF2–

DH = +5.8 kcal/mol

Table S4. Enthalpies related to hypoiodite formation. Values calculated at the M062X/QZVP
level.

S17
 d. Computed Data

i. Reactants

thiazole
Enthalpy (MP2/6-31+G*) = -567.911493
Free Energy (MP2/6-31+G*) = -567.943527
8
thiazole
C 1.21777 -0.02219 0.00000
C 0.63940 -1.27214 0.00000
N -0.73465 -1.29184 0.00000
S 0.00000 1.18388 0.00000
C -1.19983 -0.05686 0.00000
H 2.27046 0.23116 0.00000
H 1.18415 -2.20974 0.00000
H -2.25617 0.18656 0.00000

isothiazole
Enthalpy (MP2/6-31+G*) = -567.906456
Free Energy (MP2/6-31+G*) = -567.938455
8
isothiazole
S 0.00000 1.15219 0.00000
N -1.26327 0.06613 0.00000
C -0.75338 -1.17427 0.00000
H -1.45531 -2.00297 0.00000
C 0.65612 -1.28437 0.00000
H 1.20999 -2.21695 0.00000
C 1.23136 -0.02667 0.00000
H 2.28363 0.23391 0.00000

2-thiazolide
Enthalpy (MP2/6-311+G**) = -567.4146865
7
2-thiazolide
C 0.11600 -1.39573 0.00000
N 1.28412 -0.76572 0.00000
C 1.25299 0.62021 0.00000
C 0.00000 1.19214 0.00000
S -1.19858 -0.03575 0.00000
H 2.19010 1.17637 0.00000
H -0.21560 2.25589 0.00000

S18
5-thiazolide
Enthalpy (MP2/6-311+G**) = -567.4205555
7
5-thiazolide
C 1.18867 -0.10009 0.00000
N 0.64720 -1.31434 0.00000
C -0.73920 -1.18226 0.00000
C -1.36385 0.07028 0.00000
S 0.00000 1.15728 0.00000
H -1.30657 -2.11248 0.00000
H 2.26244 0.06889 0.00000

5-isothiazolide
Enthalpy (MP2/6-311+G**) = -567.4165908
7
5-isothiazolide
N -1.28008 -0.01166 0.00000
C -0.65218 -1.19911 0.00000
C 0.77175 -1.18178 0.00000
S 0.00000 1.12443 0.00000
C 1.35970 0.09581 0.00000
H -1.27266 -2.09729 0.00000
H 1.35764 -2.10158 0.00000

bromopentafluorobenzene
Enthalpy (MP2/6-311+G**) = -3298.776268
12
bromopentafluorobenzene
C 0.00000 1.19838 -0.07760
C 0.00000 -1.20474 -1.47051
C 0.00000 1.20474 -1.47051
C 0.00000 0.00000 0.63910
C 0.00000 -1.19838 -0.07760
C 0.00000 0.00000 -2.17008
F 0.00000 2.37873 0.56954
F 0.00000 2.36931 -2.14439
F 0.00000 0.00000 -3.51411
F 0.00000 -2.36931 -2.14439
F 0.00000 -2.37873 0.56954
Br 0.00000 0.00000 2.50679

1-bromoheptafluoropropane
Enthalpy (MP2/6-311+G**) = -3384.191302
11
1-bromoheptafluoropropane

S19
C -0.65570 0.77652 0.24538
C 0.76285 0.59925 -0.34731
C 1.59738 -0.61290 0.13341
F 1.12605 -1.75990 -0.38349
F 1.58307 -0.70061 1.47530
F 2.86576 -0.44983 -0.28001
F 1.45975 1.72049 -0.01727
F 0.65989 0.52421 -1.69923
F -1.17131 1.89905 -0.31688
F -0.55512 0.98443 1.57990
Br -1.82686 -0.70108 -0.09754

2-bromopentafluoropropane
Enthalpy (MP2/6-311+G**) = -3384.179974
11
2-bromopentafluoropropane
C 0.11560 0.74169 1.29832
C -0.40873 0.08569 0.00000
C 0.11560 0.74169 -1.29832
F -0.22011 2.04413 -1.33634
F -0.43745 0.13580 -2.36360
F -1.77338 0.22779 0.00000
F -0.22011 2.04413 1.33634
F -0.43745 0.13580 2.36360
F 1.45469 0.63947 -1.38186
F 1.45469 0.63947 1.38186
Br 0.07650 -1.77753 0.00000

ii. Products

2-bromothiazole
Enthalpy (MP2/6-31+G*) = -3137.357929
Free Energy (MP2/6-31+G*) = -3137.394481
8
2-bromothiazole
C 0.00000 0.25253 0.00000
N -0.26250 1.53901 0.00000
C 0.91763 2.24344 0.00000
C 2.06887 1.48874 0.00000
S 1.67276 -0.18172 0.00000
Br -1.33783 -1.05511 0.00000
H 0.88071 3.32730 0.00000
H 3.09763 1.82788 0.00000

5-bromothiazole

S20
Enthalpy (MP2/6-31+G*) = -3137.355277
Free Energy (MP2/6-31+G*) = -3137.391904
8
5-bromothiazole
C 2.01559 1.54719 0.00000
N 0.95803 2.33684 0.00000
C -0.19282 1.59153 0.00000
C 0.00000 0.22656 0.00000
S 1.67886 -0.14698 0.00000
Br -1.32517 -1.09108 0.00000
H 3.03743 1.91024 0.00000
H -1.16105 2.07971 0.00000

5-bromoisothiazole
Enthalpy (MP2/6-31+G*) = -3137.351915
Free Energy (MP2/6-31+G*) = -3137.388527
8
5-bromoisothiazole
N 2.21297 1.36435 0.00000
C 1.15868 2.19578 0.00000
C -0.12436 1.60911 0.00000
S 1.65531 -0.20455 0.00000
C 0.00000 0.23131 0.00000
Br -1.38506 -1.02566 0.00000
H -1.06949 2.14088 0.00000
H 1.36507 3.26221 0.00000

pentafluorophenyl anion
Enthalpy (MP2/6-31+G*) = -725.950058
Free Energy (MP2/6-31+G*) = -725.994210
11
pentafluorophenyl anion
C 0.00000 0.00000 -1.77629
C 0.00000 0.00000 1.07312
C 0.00000 1.14889 -1.02297
C 0.00000 -1.14889 -1.02297
C 0.00000 -1.20414 0.37296
C 0.00000 1.20414 0.37296
F 0.00000 2.40438 -1.63935
F 0.00000 2.37889 1.08726
F 0.00000 0.00000 2.43963
F 0.00000 -2.37889 1.08726
F 0.00000 -2.40438 -1.63935

pentafluorobenzene
Enthalpy (MP2/6-31+G*) = -726.507469

S21
Free Energy (MP2/6-31+G*) = -726.550420
12
pentafluorobenzene
C 0.00000 0.00000 -1.68305
C 0.00000 0.00000 1.11773
C 0.00000 1.19277 -0.96925
C 0.00000 -1.19277 -0.96925
C 0.00000 -1.20960 0.42412
C 0.00000 1.20960 0.42412
H 0.00000 0.00000 -2.76873
F 0.00000 2.37350 -1.62828
F 0.00000 2.37222 1.10261
F 0.00000 0.00000 2.46270
F 0.00000 -2.37222 1.10261
F 0.00000 -2.37350 -1.62828

(1,1,1,2,3,3,3)-heptafluoropropane
Enthalpy (MP2/6-31+G*) = -811.827549
Free Energy (MP2/6-31+G*) = -811.872345
11
(1,1,1,2,3,3,3)-heptafluoropropane
C -0.10584 -0.09786 1.29073
C -0.12042 0.72101 0.00000
C -0.10584 -0.09786 -1.29073
H -1.01164 1.35544 0.00000
F 0.97872 -0.88601 -1.38356
F -0.10584 0.74660 -2.34486
F 1.00900 1.52092 0.00000
F 0.97872 -0.88601 1.38356
F -0.10584 0.74660 2.34486
F -1.21048 -0.87145 -1.37037
F -1.21048 -0.87145 1.37037

2-heptafluoropropyl anion
Enthalpy (MP2/6-31+G*) = -811.284849
Free Energy (MP2/6-31+G*) = -811.329773
10
2-heptafluoropropyl anion
C -1.23977 -0.11475 -0.08259
C -0.00002 0.49268 -0.57531
C 1.23977 -0.11469 -0.08264
F -1.47496 -0.10557 1.30417
F -1.35492 -1.43346 -0.43109
F -2.35509 0.52373 -0.57807
F -0.00008 1.85489 -0.09626
F 2.35495 0.52467 -0.57718

S22
F 1.35559 -1.43309 -0.43215
F 1.47453 -0.10667 1.30427

(1,1,2,2,3,3,3)-heptafluoropropane
Enthalpy (MP2/6-31+G*) = -811.827549
Free Energy (MP2/6-31+G*) = -811.872345
11
(1,1,2,2,3,3,3)-heptafluoropropane
C -1.35887 0.33167 -0.45955
C -0.18727 -0.48253 0.10109
C 1.19342 0.18118 -0.06200
H -1.28345 0.48297 -1.53750
F -2.50675 -0.34924 -0.18019
F -1.40230 1.54347 0.16907
F -0.15257 -1.66596 -0.58043
F 1.35085 0.56004 -1.35277
F 1.30808 1.26372 0.72139
F 2.16388 -0.68959 0.25474
F -0.38345 -0.73632 1.41934

1-heptafluoropropyl anion
Enthalpy (MP2/6-31+G*) = -811.252997
Free Energy (MP2/6-31+G*) = -811.297875
10
1-heptafluoropropyl anion
C 1.35143 0.35286 -0.66456
C 0.25855 -0.41423 0.06445
C -1.15588 0.17305 -0.09589
F -1.52717 0.26296 -1.39171
F -1.27788 1.39789 0.45841
F -2.07435 -0.62980 0.51839
F 0.40703 -0.58009 1.44913
F 0.17714 -1.69690 -0.44712
F 2.52992 -0.38257 -0.26337
F 1.46258 1.55405 0.14027

2-(pentafluoro)phenyl-thiazole
Enthalpy (6-311+G**) = -1293.737116
18
2-thiazolide and bromopentafluorobenzene SNAr product
C -0.7987070000 3.7682280000 0.0000000000
C -2.1468580000 3.4732670000 0.0000000000
C -0.6489900000 1.5545540000 0.0000000000
N 0.0399490000 2.6936950000 0.0000000000
S -2.3820140000 1.7824140000 0.0000000000
H -0.3779550000 4.7680450000 0.0000000000

S23
H -2.9863760000 4.1584570000 0.0000000000
C 1.4034840000 0.0904320000 0.0000000000
C -0.1378580000 -2.2202420000 0.0000000000
C 0.0000000000 0.2395990000 0.0000000000
C 2.0143780000 -1.1628060000 0.0000000000
C 1.2489570000 -2.3253320000 0.0000000000
C -0.7296940000 -0.9621330000 0.0000000000
F 2.2291780000 1.1493550000 0.0000000000
F 3.3572400000 -1.2533120000 0.0000000000
F 1.8412530000 -3.5318080000 0.0000000000
F -0.9012090000 -3.3289680000 0.0000000000
F -2.0855030000 -0.9279770000 0.0000000000

5-(pentafluoro)phenyl-thiazole
Enthalpy (6-311+G**) : -1293.737971
18
5-thiazolide and bromopentafluorobenzene SNAr Product
S 0.0000000000 0.2351670994 1.0143490651
C 0.0000000000 0.2230355215 -0.7024692496
N 0.0000000000 1.4088724132 -1.2832339662
C 0.0000000000 2.3941138807 -0.3363404499
C 0.0000000000 1.9720766958 0.9931998131
H 0.0000000000 -0.7132755709 -1.2505361614
H 0.0000000000 3.4237263192 -0.6647874153
C 0.0000000000 2.7935636714 2.2070973772
C 0.0000000000 4.3988786531 4.5746067297
C 0.0000000000 2.2442284046 3.5025405464
C 0.0000000000 4.2012259304 2.1710048836
C 0.0000000000 4.9926737970 3.3157147617
C 0.0000000000 3.0108654110 4.6636200975
F 0.0000000000 6.3342828836 3.2071711054
F 0.0000000000 2.4121597527 5.8690581527
F 0.0000000000 4.8599092829 0.9906353087
F 0.0000000000 0.9002648020 3.6680074075
F 0.0000000000 5.1544410525 5.6848019937

5-(pentafluoro)phenyl-isothiazole
Enthalpy (6-311+G**) : -1293.730183
18
5-isothiazolide and bromopentafluorobenzene SNAr Product
C -3.7924660000 0.8723280000 0.5638300000
C -1.6477600000 0.1644980000 0.1220390000
S -2.7017580000 -0.9295330000 -0.6864700000
H -4.6127990000 1.4590020000 0.9672470000
C 0.6030940000 1.2291210000 -0.0874960000
C 1.8867170000 -1.2164030000 0.1405700000

S24
C -0.1879650000 0.0824860000 0.0801300000
C 1.9940710000 1.1791490000 -0.0852560000
C 2.6384690000 -0.0553880000 -0.0286670000
C 0.4972830000 -1.1392260000 0.1405920000
F 0.0188690000 2.4436280000 -0.1891990000
F 2.7171790000 2.3044830000 -0.2311680000
F 3.9804380000 -0.1180430000 -0.0537060000
F 2.5037050000 -2.4087290000 0.2254880000
F -0.1995480000 -2.2894810000 0.2839110000
N -4.1052830000 -0.1871870000 -0.2022570000
C -2.4228680000 1.1174800000 0.7784100000
H -2.0193230000 1.9328410000 1.3692180000

S25
 iii. Transition States and Post-Transition States

2-thiazolide and bromopentafluorobenzene SN2@Br post-transition state

Enthalpy (MP2/6-31+G*) = -3866.354524
19
2-thiazolide and bromopentafluorobenzene transition state
C -5.68835 0.35086 0.01965
C -3.32064 -0.25095 -0.01099
S -4.22081 1.24256 0.07015
H -6.65974 0.83041 0.04527
C 1.24734 -0.13051 -0.00352
C 4.07722 0.15513 0.00208
C 1.87853 1.09290 -0.01577
C 2.10910 -1.20390 0.01107
C 3.50246 -1.11337 0.01545
C 3.26136 1.28364 -0.01261
F 5.43402 0.29172 0.00517
F 1.13464 2.26576 -0.03150
F 3.84809 2.52170 -0.02509
F 4.32446 -2.20921 0.03031
F 1.61506 -2.50028 0.02439
Br -1.38042 -0.23015 -0.00867
N -4.07307 -1.33277 -0.07161
C -5.40661 -0.99521 -0.05432
H -6.15003 -1.78549 -0.09869

5-thiazolide and bromopentafluorobenzene SN2@Br post-transition state

Enthalpy (MP2/6-311+G**) = -3866.355627
19
5-thiazolide and bromopentafluorobenzene transition state
C -5.70280 0.21452 -0.00186
N -5.46562 -1.08779 0.01661
C -4.10829 -1.31265 0.01956
C -3.29573 -0.19388 0.00344
S -4.29383 1.21208 -0.01627
C 1.23298 -0.05647 -0.00131
C 4.07088 0.07425 -0.00223
C 2.03269 -1.17675 -0.00858
C 1.92647 1.13275 -0.00190
C 3.31771 1.24571 0.00879
C 3.42852 -1.16153 0.00201
F 5.43232 0.13693 0.00158
F 1.46586 -2.44239 -0.01198
F 4.18897 -2.30018 -0.00419

S26
F 3.97056 2.44936 0.00924
F 1.24605 2.34113 0.00175
Br -1.33581 -0.12418 0.00122
H -3.73285 -2.33069 0.03380
H -6.70133 0.63879 -0.00760

5-isothiazolide and bromopentafluorobenzene SN2@Br post-transition state

Enthalpy (MP2/6-311+G**) = -3866.242939
19
5-isothiazolide and bromopentafluorobenzene transition state
C -5.45315 0.99282 0.05896
N -5.76703 -0.31221 -0.01453
S -4.32936 -1.17308 -0.06490
C -4.08207 1.32766 0.07648
C -3.29383 0.18785 0.01044
H -6.27801 1.70087 0.10007
H -3.67767 2.33350 0.13242
C 1.23837 0.02395 -0.00275
C 4.07912 -0.03765 -0.00107
C 2.01124 1.16308 -0.01826
C 1.96076 -1.14799 0.00831
C 3.35445 -1.22692 0.01772
C 3.40692 1.18215 -0.00929
Br -1.33721 0.08653 0.00243
F 1.41384 2.41502 -0.03265
F 4.13919 2.33896 -0.02407
F 5.44163 -0.06729 0.00296
F 4.03598 -2.41420 0.02931
F 1.31007 -2.37226 0.02214

2-thiazolide and 1-bromoheptafluoropropane SN2@Br post-transition state

Enthalpy (MP2/6-311+G**) = -3951.735101
18
2-thiazolide and 1-bromoheptafluoropropane transition state
C -4.71570 1.07184 -0.72642
C -5.12541 0.43955 0.42736
S -3.80610 -0.43565 1.09443
N -3.39920 0.87766 -1.08402
C -2.76912 0.09771 -0.22238
C 1.48221 -1.04761 -0.38805
C 2.52504 -0.27278 0.40111
C 2.60301 1.23707 0.10530
F 1.46627 1.86772 0.44692
F 3.61098 1.79340 0.82984
F 2.85617 1.48325 -1.19566
F 3.81444 -0.75218 0.22051

S27
F 2.24902 -0.38255 1.74220
F 1.94335 -1.05837 -1.71341
F 1.63092 -2.37106 0.05686
Br -0.74262 -0.44880 -0.30062
H -5.34844 1.69599 -1.35219
H -6.10831 0.46211 0.88407

5-thiazolide and 1-bromoheptafluoropropane SN2@Br post-transition state

Enthalpy (MP2/6-311+G**) = -3951.738462
18
5-thiazolide and 1-bromoheptafluoropropane transition state
C -2.76726 -0.04777 0.17864
C -3.48388 0.19459 1.33929
N -4.81273 0.55122 1.21995
C -5.14190 0.58970 -0.06414
S -3.85011 0.19440 -1.14102
H -3.05448 0.11984 2.33467
H -6.13606 0.84748 -0.41563
C 2.55907 -0.17092 0.37304
C 1.49092 -1.10903 -0.17201
C 2.53253 1.27421 -0.16292
F 1.74634 -2.33025 0.45864
F 1.81178 -1.31460 -1.51683
F 2.42284 -0.07561 1.73469
F 3.84081 -0.63474 0.12881
F 3.59782 1.95982 0.32973
F 2.61117 1.31220 -1.50815
F 1.42162 1.92489 0.22054
Br -0.67792 -0.56846 0.00627

5-isothiazolide and 1-bromoheptafluoropropane SN2@Br post-transition state

Enthalpy (MP2/6-311+G**) = -3951.726695
18
5-isothiazolide and 1-bromoheptafluoropropane transition state
C -2.99924 0.08163 0.07337
C -3.85037 0.97911 0.70798
C -5.18613 0.51395 0.74719
N -5.43457 -0.68311 0.18704
S -3.95879 -1.24396 -0.40543
H -3.51605 1.92635 1.12431
H -6.03019 1.03983 1.19088
C 3.38544 -0.74903 0.16213
C 2.31689 0.30544 0.50944
C 1.30636 0.68020 -0.60174
Br -0.87135 0.32649 -0.22142
F 4.16477 -0.99296 1.24877

S28
F 2.82765 -1.91879 -0.20343
F 4.20030 -0.32013 -0.82350
F 1.68373 -0.03345 -1.74736
F 1.53627 2.01335 -0.92292
F 3.00719 1.40079 0.96961
F 1.64550 -0.21281 1.59236

2-thiazolide and 2-bromoheptafluoropropane SN2@Br post-transition state

Enthalpy (MP2/6-311+G**) = -3951.629501
18
2-thiazolide and 2-bromoheptafluoropropane transition state
C -2.44943 -1.21047 0.02394
C -1.80529 0.04596 -0.41262
C -2.27730 1.26745 0.27245
F -3.63411 1.56720 0.17822
F -1.66158 2.38137 -0.23299
F -2.11017 0.20775 -1.79888
F -3.83349 -1.29542 -0.10969
F -1.98514 -2.27527 -0.69862
F -2.01536 1.23480 1.61153
F -2.20501 -1.47618 1.34002
Br 0.75579 -0.13992 -0.11044
C 5.10547 0.21629 0.06586
C 2.70588 -0.25077 0.04422
C 4.73610 -1.07066 0.38933
N 3.38533 -1.33175 0.37651
S 3.70197 1.14828 -0.27111
H 6.10485 0.63219 0.01529
H 5.42468 -1.87003 0.64676

2-thiazolide and bromopentafluorobenzene SNAr Transition State

Enthalpy (MP2/6-311+G**)= -3866.216158
Frequency = -241.79 cm-1
19
2-thiazolide and BrpentafluoroBenz SnAr TS
C -1.9445320000 -1.1793340000 0.5439900000
C 0.1175570000 -1.4976400000 -0.6715300000
C 0.0895310000 -0.1181000000 1.2747600000
C -1.2701500000 -0.3463660000 1.4346200000
C -1.2412140000 -1.7282960000 -0.5280800000
C 0.7770490000 -0.5393010000 0.1209700000
Br 2.6747890000 -0.5270470000 0.1857600000
C 0.5596450000 1.4343890000 -1.1013800000
N 0.8427780000 2.4722080000 -0.3271200000
C -0.1930500000 3.3592210000 -0.1070300000
S -1.2213250000 1.5914840000 -1.6162600000

S29
C -1.3903110000 3.0417950000 -0.7154000000
H -2.3072990000 3.6207470000 -0.6780300000
F 0.7027130000 0.6738390000 2.1833400000
F -1.9323790000 0.1633360000 2.5034100000
F -3.2680530000 -1.4377900000 0.6998700000
F -1.8868660000 -2.5510440000 -1.3956100000
F 0.7552750000 -2.0409910000 -1.7357400000
H -0.0319370000 4.2323310000 0.5235000000

5-thiazolide and bromopentafluorobenzene SNAr Transition State

Enthalpy (MP2/6-311+G**) = -3668.219702
Frequency = -207.56 cm-1
19
thiazol-5-ide and pentafluorobromobenzene SNAr TS
C -2.32660 -0.50040 0.41863
C -0.44163 -1.41072 -0.78106
C -0.09245 -0.27002 1.29009
C -1.45551 -0.02725 1.39578
C -1.80300 -1.16625 -0.68993
C 0.46066 -0.81202 0.11582
Br 2.23992 -1.47354 0.19879
C 1.04566 1.21753 -0.97125
C 1.76402 2.11426 -0.17305
N 1.29232 3.39822 0.05453
S -0.35338 2.13502 -1.45184
C 0.13276 3.54926 -0.57698
H 2.69930 1.84229 0.31419
H -0.43371 4.47620 -0.56566
F 0.71813 0.19616 2.26713
F -1.95699 0.59253 2.49392
F -3.66435 -0.30023 0.53054
F -2.65002 -1.64412 -1.63872
F 0.02452 -2.05087 -1.87807

5-isothiazolide and bromopentafluorobenzene SNAr Transition State

Enthalpy (MP2/6-311+G**)= -3866.214047
Frequency = -219.83 cm-1
19
5-isothiazolide and BrpentafluoroBenz SnAr TS
C -2.3885080000 -0.2037640000 0.3934800000
C -0.6321210000 -1.3079120000 -0.8380000000
C -0.1620380000 -0.3484690000 1.3001900000
C -1.4780500000 0.0789820000 1.4080200000
C -1.9461640000 -0.8780810000 -0.7453900000
C 0.3296260000 -0.8860760000 0.0970700000
Br 2.0070920000 -1.7790050000 0.1511300000

S30
C 1.1810930000 1.1120790000 -0.8526300000
C 2.0180880000 1.8548050000 -0.0070100000
C 1.6758390000 3.2303930000 0.0979500000
S 0.0417050000 2.2602620000 -1.4010400000
N 0.6045160000 3.6525560000 -0.5953700000
F 0.6914510000 -0.0548640000 2.3091400000
F -1.9067140000 0.6955390000 2.5378300000
F -3.6876310000 0.1695180000 0.5082800000
F -2.8362020000 -1.1793870000 -1.7260000000
F -0.2384070000 -1.9380100000 -1.9690600000
H 2.2064340000 3.9700060000 0.6984400000
H 2.8574010000 1.4161800000 0.5324600000

iv. 3-Cyanopyridine Data

3-cyanopyridine
Enthalpy (MP2/6-31+G*) = -339.419593
Free Energy (MP2/6-31+G*) = -339.457481
12
3-cyanopyridine
C 0.00000 -0.02002 1.01355
C 0.00000 -1.20923 1.75570
C 0.00000 1.18448 1.71369
C 0.00000 1.15570 3.11168
C 0.00000 -1.14153 3.15880
N 0.00000 0.01866 3.83397
C 0.00000 -2.48595 1.09869
N 0.00000 -3.53808 0.55471
H 0.00000 -2.05195 3.75522
H 0.00000 2.07933 3.68672
H 0.00000 2.13468 1.18590
H 0.00000 -0.04774 -0.07353

4-bromo-3-cyanopyridine
Enthalpy (MP2/6-31+G*) = -2908.871843
Free Energy (MP2/6-31+G*) = -2908.913759
12
4-bromo-3-cyanopyridine
C 0.00000 0.44104 0.00000
C 0.99180 -0.55049 0.00000
C 0.39227 1.77842 0.00000
C 1.75713 2.07192 0.00000
C 2.33934 -0.14547 0.00000
N 2.72769 1.13687 0.00000

S31
C 0.67445 -1.94682 0.00000
N 0.43157 -3.10639 0.00000
H 2.09359 3.10660 0.00000
H -0.34655 2.57498 0.00000
H 3.12756 -0.89629 0.00000
Br -1.82626 -0.02544 0.00000

5-bromo-3-cyanopyridine intermediate
Enthalpy (MP2/6-31+G*) = -2909.344218
Free Energy (MP2/6-31+G*) = -2909.387796
13
5-bromo-3-cyanopyridine intermediate
C -0.38238 1.69755 0.40113
C -0.54197 0.31904 0.92320
C 0.69154 -0.46887 0.84740
C 1.69145 -0.02303 0.06188
C 1.62298 1.24348 -0.54940
N 0.59828 2.10323 -0.31574
C 2.92229 -0.79658 -0.07322
N 3.89475 -1.39281 -0.18427
H 2.42279 1.59966 -1.18960
H -1.18412 2.40529 0.60769
H -1.03317 0.28963 1.89733
H 0.74838 -1.42094 1.36625
Br -1.95510 -0.56217 -0.25279

2-bromo-3-cyanopyridine intermediate
Enthalpy (MP2/6-31+G*) = -2909.343661
Free Energy (MP2/6-31+G*) = -2909.387344
13
2-bromo-3-cyanopyridine intermediate
C 0.06713 0.18677 -0.79834
C 0.84222 -0.85306 -0.08218
C 1.94906 -0.52389 0.63723
C 2.37998 0.79692 0.61860
C 1.70754 1.72396 -0.26528
N 0.68156 1.46758 -0.96172
Br -1.59491 0.48860 0.30373
H -0.34227 -0.16641 -1.74725
H 2.49403 -1.28204 1.19288
H 3.24497 1.12159 1.18671
H 2.13895 2.71937 -0.38032
C 0.41132 -2.22855 -0.19894

S32
N 0.08906 -3.32014 -0.32320

6-bromo-3-cyanopyridine intermediate
Enthalpy (MP2/6-31+G*) = -2909.343667
Free Energy (MP2/6-31+G*) = -2909.387037
13
6-bromo-3-cyanopyridine intermediate
C -0.68543 -0.11681 -0.95729
C 0.05394 -1.36111 -0.65454
C 1.31505 -1.30429 -0.15981
C 1.90250 -0.04835 -0.00670
C 1.21721 1.11908 -0.53843
N 0.04749 1.11398 -1.00654
Br -2.06545 0.07458 0.48966
H -1.30605 -0.20833 -1.85132
H 1.86183 -2.20314 0.11053
H 1.76678 2.06172 -0.55749
C 3.25502 0.09801 0.46247
N 4.33231 0.22096 0.83133
H -0.46074 -2.30684 -0.79316

4-bromo-3-cyanopyridine intermediate
Enthalpy (MP2/6-31+G*) = -2909.339112
Free Energy (MP2/6-31+G*) = -2909.382621
13
4-bromo-3-cyanopyridine intermediate
C 1.77048 1.81717 0.10307
C 0.63702 1.54545 0.80177
C 0.06144 0.19077 0.79569
C 0.91488 -0.77323 0.07614
C 2.03435 -0.37879 -0.55464
N 2.48262 0.90553 -0.58565
C 0.56469 -2.17976 0.14091
N 0.29495 -3.28864 0.22403
Br -1.71131 0.30733 -0.16174
H 2.65919 -1.10165 -1.07261
H 2.17231 2.82665 0.08520
H 0.11262 2.32735 1.34185
H -0.24264 -0.16515 1.78507

3-cyanopyridin-2-ide anion
Enthalpy (MP2/6-31+G*) = -338.814938
Free Energy (MP2/6-31+G*) = -338.852804

S33
11
3-cyanopyridin-2-ide anion
C 0.00000 -0.03341 1.02461
C 0.00000 -1.19894 1.81058
C 0.00000 1.18820 1.69480
C 0.00000 1.15429 3.09151
C 0.00000 -1.23800 3.24940
N 0.00000 0.02447 3.83539
C 0.00000 -2.45648 1.10328
N 0.00000 -3.46723 0.48215
H 0.00000 2.09269 3.65534
H 0.00000 2.13593 1.15640
H 0.00000 -0.08178 -0.06671

3-cyanopyridin-4-ide anion
Enthalpy (MP2/6-31+G*) = -338.830677
Free Energy (MP2/6-31+G*) = -338.868335
11
3-cyanopyridin-4-ide anion
C 0.00000 -0.00139 0.89196
C 0.00000 -1.15547 1.72487
C 0.00000 1.15634 1.71255
C 0.00000 1.13643 3.11425
C 0.00000 -1.13654 3.13506
N 0.00000 0.00270 3.85040
C 0.00000 -2.47115 1.12039
N 0.00000 -3.56262 0.65610
H 0.00000 -2.06527 3.71224
H 0.00000 2.06632 3.69108
H 0.00000 2.14543 1.24229

3-cyanopyridin-5-ide anion
Enthalpy (MP2/6-31+G*) = -338.827894
Free Energy (MP2/6-31+G*) = -338.866073
11
3-cyanopyridin-5-ide anion
C 0.00000 0.00421 1.03752
C 0.00000 -1.20882 1.76663
C 0.00000 1.27301 1.66221
C 0.00000 1.14332 3.07575
C 0.00000 -1.15610 3.17019
N 0.00000 0.00843 3.83902
C 0.00000 -2.48197 1.10740

S34
N 0.00000 -3.53013 0.54855
H 0.00000 -2.07153 3.76484
H 0.00000 2.04583 3.69477
H 0.00000 -0.07646 -0.05455

3-cyanopyridin-6-ide anion
Enthalpy (MP2/6-31+G*) = -338.811275
Free Energy (MP2/6-31+G*) = -338.849654
11
3-cyanopyridin-6-ide anion
C 0.00000 -0.02550 1.01289
C 0.00000 -1.22600 1.74230
C 0.00000 1.16474 1.74124
C 0.00000 1.25828 3.17220
C 0.00000 -1.13819 3.14377
N 0.00000 0.02480 3.82523
C 0.00000 -2.50045 1.09005
N 0.00000 -3.55575 0.54692
H 0.00000 -2.05628 3.73894
H 0.00000 2.10139 1.17950
H 0.00000 -0.04596 -0.07941

v. 2-Thiazolide Ring Opening Data

2-thiazolide ring opening TS

Enthalpy (MP2/6-311+G**) = -567.263304
Frequency: -303.62
7
2-thiazolide ring opening TS
S -0.1036124089 2.2400893821 2.0169442689
C 0.1808567721 2.6950034977 -0.3312349825
C 0.1866424818 1.4360475266 -0.7192968571
H 0.2751481481 3.6096904485 -0.9045938606
H 0.2863550819 0.9923055560 -1.7042435812
C -0.0877751924 0.7172986129 1.4708030848
N 0.0342851135 0.2600149763 0.2881619274

2-thiazolide ring open product (cis-3-sulfanylacrylonitrile anion)

Enthalpy (MP2/6-311+G**) = -567.4715113
7
2-thiazolide ring open product
C 0.0000000000 -0.1483266181 1.1493033284

S35
C 0.0000000000 -0.0849033773 -0.2314159095
S 0.0000000000 -1.4931131539 2.1843721284
H 0.0000000000 0.8398208180 1.6262560462
H 0.0000000000 0.8858044546 -0.7249055947
C 0.0000000000 -1.2173340077 -1.0859713646
N 0.0000000000 -2.1043481156 -1.8807186342

Scheme S1. Proposed rearrangement and ring opening of 2-thiazolide anion.

Figure S14. Energy profile for the ring opening of 2-thiazolide shows a transition state barrier of
greater than 30 kcal/mol. Although the overall opening is exothermic, our system does not have
the intrinsic energy to overcome this barrier.

vi. Hypoiodite Data

S36
t-BuOI
Enthalpy (M062x/QZVP) = -530.541192
Free Energy (MP2/6-31+G*) = -530.583113
15
t-BuOI
C -1.67980 1.25817 0.87685
C -1.63605 0.00004 0.02265
C -1.68030 -1.25750 0.87771
C -2.77907 -0.00008 -0.98739
H -2.62141 1.30630 1.42163
H -0.86968 1.26928 1.60484
H -1.59496 2.14207 0.24689
H -0.87095 -1.26787 1.60654
H -1.59454 -2.14185 0.24855
H -2.62248 -1.30563 1.42162
H -2.72186 0.88366 -1.61911
H -3.73475 0.00048 -0.46555
H -2.72232 -0.88453 -1.61818
O -0.47610 -0.00069 -0.83129
I 1.31723 -0.00000 -0.01766

t-BuO–
Enthalpy (M062x/QZVP) = -232.935902
Free Energy (MP2/6-31+G*) = -232.971690
14
t-BuO–
C -0.84732 -1.17116 -0.43264
C 0.00005 -0.00001 0.14535
C 1.43796 -0.14814 -0.43273
C -0.59071 1.31930 -0.43266
H -0.87171 -1.20423 -1.52874
H -0.43733 -2.11089 -0.05746
H -1.86797 -1.07598 -0.05695
H 1.86598 -1.07961 -0.05708
H 2.04668 0.67689 -0.05761
H 1.47875 -0.15269 -1.52884
H -1.60967 1.43371 -0.05774
H -0.60691 1.35699 -1.52876
H 0.00164 2.15581 -0.05675
O 0.00008 0.00001 1.48075
CF3CF2CF2CF2I
Enthalpy (M062x/QZVP) = -1348.746570
Free Energy (MP2/6-31+G*) = -1348.802544

S37
14
CF3CF2CF2CF2I
I -2.67485 -0.30477 -0.02461
C -0.80803 0.73646 0.12879
C 0.38843 -0.23392 -0.03243
C 1.75544 0.49383 -0.17823
C 2.97569 -0.42539 0.08689
F -0.73381 1.33123 1.31763
F -0.72885 1.67377 -0.81806
F 0.20892 -0.97879 -1.12668
F 0.42853 -1.03355 1.04020
F 1.85912 0.96104 -1.42499
F 1.82780 1.51807 0.67905
F 2.86037 -1.55362 -0.59923
F 3.08080 -0.70764 1.37463
F 4.07466 0.20356 -0.30096

CF3CF2CF2CF2–
Enthalpy (M062x/QZVP) = -1051.131974
Free Energy (MP2/6-31+G*) = -1051.182964544
13
CF3CF2CF2CF2–
C -2.30928 0.32205 0.04515
C -0.82925 0.62569 0.26225
C 0.24032 -0.48345 0.03921
C 1.69799 0.01781 -0.11564
F -2.38184 0.02183 -1.33604
F -2.44469 -0.96523 0.63475
F -0.63578 1.02436 1.55051
F -0.45771 1.66648 -0.53458
F 0.25466 -1.32796 1.08733
F -0.01219 -1.19796 -1.07047
F 2.03892 0.85498 0.85923
F 1.89678 0.62445 -1.28034
F 2.54199 -1.02234 -0.06435

S38
 e. Transition State Geometries

Figure S15. Post-transition state geometry of the SN2@Br reaction between 5-thiazolide and
bromopentafluorobenzene shows that there is a linear transition state, and the transition state is
closer to the products than the reactants along the reaction coordinate pathway.

S39
Figure S16. Transition state geometry of the SNAr reaction, losing bromide, between 5-
thiazolide and bromopentafluorobenzene shows that the transition state is early on the reaction
coordinate pathway, meaning that the transition state is closer to the reactants than the products.
To form this transition state, the nucleophile must attack the substrate directly on the pi-system,
perpendicular to the carbon-bromine bond, limiting the area of attack available for the
nucleophile.

S40