Stabilizing Transition Metal-Arylthiolate Bonds via Secondary Sphere Hydrogen

Stabilizing Transition Metal-Arylthiolate Bonds via Secondary Sphere Hydrogen

Stabilizing Transition Metal-Arylthiolate Bonds via Secondary Sphere Hydrogen Bonding
Ryan L. Hall and Samuel Pazicni. Department of Chemistry, University of New Hampshire.
Introduction

Characterization

Cu (II) Arylthiolate Binding

Metal-sulfur bonds are common motifs in the active sites of enzymes.

During complexation with a metal, H3thpa undergoes tautomerization to give a structure with three hydrogen

Metalloenzyme active sites are also known to be hydrogen-bond rich, and

bonding donors situated above an open coordination site. Attempted arylthiolate complexation in this cavity

these interactions are theorized to play a significant role in enzymatic activity.

resulted in the previously reported copper fluoride complex (Fig. 5). Fluoride abstraction from BF has been

This work aims to create simple model complexes containing a metal-sulfur

shown to occur in protic solvents3. Aprotic conditions were used to minimize the risk of fluoride abstraction.

bond in a hydrogen-bond rich environment, so that the impact of secondary

Attempted reaction as shown in Figure 6 also yields a fluoride complex.

O

ylmethyl)amine (H3thpa), to copper. Thiolate binding was attempted in both

remained elusive, though previously reported metal-fluoride-H 3thpa

HO
complexes

O
NH

binding presents additional challenges, and new

1. CuSO4 * 5H2O
NaBF4
MeOH

HN
N

2. NaSPh

Figure 1: H3thpa in its 2hydroxypyridine tautomer.

Ligand Synthesis
O

O
N

Br

AIBN
AcOH
hv (visible)

1

O

NH

O

NH

1. CuSO4
MeCN

PF6

OH
N

HN

7

2. NaSPh
3. NaPF6

N

4

OH

2

N

400 MHz 1H NMR (CDCl3): 7.54 (1H, dd, Ar-H), 6.98 (1H, d, Ar-H), 6.65 (1H, d, Ar-H),
4.45 (2H, s, CH2), 3.94 (3H, s, OCH3). Percent Yield: 65%

N

OH
F
Cu

3

Br

(NH4)2CO3
MeCN

N

N

O

PF6

3

Figure 3: Condensation of three units of 2 to afford tpaOMe 3
400 MHz 1H NMR (CDCl3): 7.53 (3H, t, Ar-H), 7.23 (3H, d, Ar-H), 6.59 (3H, d, Ar-H),
3.92 (9H, s, OCH3), 3.83 (6H, s, CH2). Percent Yield: 47%

N

single crystal X-ray diffraction. This differs from the reported synthesis

N

where CsF is used as the fluoride source2. Aprotic conditions, employed to

8

minimize the risk of fluoride abstraction, also yielded a fluoride complex

Cl
SH

N
N

N

O

H
N

H
N

O

O

t

3

3

NaO Bu
DMF

seen as shown in Figure 8.

O

4

3

Figure 4: Demethylation in triplicate of 3 to afford pyridone tautomer of H3thpa 4
400 MHz 1H NMR (DMSO-d6): 11.85 (3H, s, NH), 7.35 (3H, dd, Ar-H), 6.22 (3H,
d, Ar-H), 6.13 (3H, d, Ar-H), 3.40 (6H, s, CH2). Percent Yield: 28%

NH

O

NH

HN
N

4

Cu(NH3)2

CuSPh
Solvent*
N2

+

(Colorless)

N

Cu

The previously reported CuF(H3thpa)BF4 was synthesized and verified via

attempted with three different solvents: benzene, toluene, and acetonitrile. Only starting material was

1. NH2OH*HCl
NH
(conc.)
3
CuSO4*5H2O
H2O
(Blue)
N2 , 0oC

HO

HO

CuF(H3thpa)PF6. Reactions with CuSPh and H3thpa have yielded only
starting material.

To circumvent the use of a counter-ion, CuSPh was synthesized according to established procedure as

3

N

X-ray diffraction.

Summary

Acknowledgements

shown in Figure 7 below. CuSPh was then combined with H 3thpa and heated to reflux. Three trials were

2

D

BF4

OH
F

Figure 6: Reaction of H3thpa with
copper (II) and NaSPh with NaPF6 to
give CuSPh(H3thpa)PF6 7 instead of
the desired CuSPh(H3thpa)PF6 8

Cu (I) Arylthiolate Binding
O

H

N

N

Figure 2: Wohl-Ziegler bromination of 1 to afford 2-bromomethyl-6-methoxypyridine 2.

N

H

CH3 E

C

OH
S HO
N
OH
N
Cu
N

O

O

Figure 10: FT-IR spectrum of
compound 6 whose structure
was verified by single crystal

6

NBS
CCl4

H

Figure 5: Reaction of H3thpa with
copper (II) and NaSPh in NaBF4 to
give CuF(H3thpa)BF4 6 instead of
CuSPh(H3thpa)BF4 5

BF4

N

N

the reported synthesis of similar

N

B

OH
F HO
N
OH
N
Cu
N

N

copper-H3thpa complexes1,2.

D

Figure 9: 1H NMR spectra of
starting material 1 (top) and
brominated compound 2
(bottom).
H2
Br C

5

N

experimental conditions are sought to replace

H
H

CH3 E

A

N

4

N

OH

H

O

C

OH
S HO
N
OH
N
Cu
N

O

NH

N

were synthesized by new means. Thiolate

B

N

BF4

were used to bind the tetradentate ligand of interest, tris(6-hydroxypyrid-2-

OH

H3C

4

sphere hydrogen bonding can be evaluated. Various synthetic approaches

copper (II) and copper (I) systems. The metal-thiolate-H 3thpa complex has

A

2. HSPh

CuSPh
(Yellow)

Starting Material (H3thpa)

Figure 7: Synthetic scheme to
CuSPh using established
procedure4.

Figure 8: Reaction of H3thpa with
CuSPh to yield only starting
material. Solvents* used:
benzene, toluene, acetonitrile.

Kyle Rodriguez (UNH)
UNH Department of Chemistry
SURF: UNH Hamel Center
University Instrumentation
Center (UNH)

Norris-Richards Undergraduate
Research Scholarship:
=Northeast Section ACS
Christian Tooley (UNH)
Jon Briggs

References
1. Moore,C.; Quist, D.; Kampf, J.; Szymczak, N. A 3-Fold-Symmetric Ligand
Based on 2-hydroxypyridine. Inorg Chem., 2014, 53, 3278-3280.
2. Moore, C.; Szymczak, N. Chem. Commun., 2015, 51, 5490- 5492.
3. Kannan, S..; Moody, M.; Barnes, C.; Duval, P. Inorg. Chem., 2006, 45 (23),
9206-9212.
4. Nguyen, L.; Dellinger, M.; Lee, J.; Quinlan, R.; Rheingold, A.; Pike, R.
Convenient synthesis of copper (I) thiolates and related compounds. Inorg.
Chim. Acta, 2005. 358 (4), 1331-1336.

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