radical stability

Radical Stability

Hendrik ZipseDepartment of ChemistryLMU München, Germany

2020

Radical Stability - Some Terminology

O H• O N•

hydroxylTEMPO

(tetramethylpiperidine-1-oxyl)"transient"

"persistent"

Radical Stability - Some Terminology

O H• O N•

hydroxylTEMPO

(tetramethylpiperidine-1-oxyl)"transient"

"persistent"

Thermodynamics Kinetics

RH + •X

DG < 0

"unstable R•"

RH + •X

R• + HX

"stable R•"large DG≠ =R• + HX

RH + •X

DG > 0

"stable R•"

"unstable R•"small DG≠ =

Radical Stability - Some Definitions

•CH3 + R-H CH4 + R•DHrxn

Radical stabilization energy (RSE) = -17.0 kJ/mol

H-CH3 •CH3 + H•BDE(C-H)

+438.98 ± 0.06 kJ/mol[a]

H-CH2CH3 •CH2CH3 + H•BDE(C-H)

+421.96 ± 0.27 kJ/mol[a]

•CH3 + CH3CH3 CH4 + CH3CH2•DHexp =

-17.0 kJ/mol[a]

[a] ATcT database, 1.122p (2020)




-17.0 kJ/mol


VB Theory

HH H

H

H

•

HH H

H

H •

MO Theory

HH H

H

H

HH H

H

H




-17.0 kJ/mol[a]

2 •CH3 + R-R CH3-CH3 + 2 R•DHrxn

2 •CH3 + CH3CH2-CH2CH3 CH3-CH3 + 2 CH3CH2•DHexp =

-11.1 kJ/mol[a]


Two radicals involved! RSE = -5.6 kJ/mol


Mechanisms of Radical Stabilization I

- Inductive Effects -

-70-60-50-40-30-20-100

RSE(kJ/mol)

•CH3 •CH2CH3

•

•

•

•

•

+10

•F •Cl

•F3C

DH298(G3(MP2)-RAD) [kJ/mol]

Mechanisms of Radical Stabilization II

- Resonance Stabilization -

-90-80-70-60-50-40-30-20-10

RSE(kJ/mol)•

0

•CH3

•

• NH

O

• O

O

•

O

N

•O

O

• H

O

C• N

•

O

•

• O

• C N


Resonance Stabilization

•CH3 + CH4 +DH298 =

-72.0 kJ/mol

VB TheoryMO Theory

•

• •

H

Mechanisms of Radical Stabilization III

- Lone Pair Donors -

-70-60-50-40-30-20-100

RSE(kJ/mol)

•CH3 •CH2CH3

+10

•CH2-Cl•CH2-Br•CH2-F

•CH2-OH•

O

O

•

O

•

S

•CH2-NH2

•

NH

O

N•


Lone-Pair Stabilization

•CH3 + CH4 +DH298 =

-46.1 kJ/mol

VB TheoryMO Theory

N•

N

H

N•

N•

-70-60-50-40-30-20-100

RSE(kJ/mol)

•CH3 •CH2CH3

•

•

+10

Multiple Substituents - Saturation


-70-60-50-40-30-20-100

RSE(kJ/mol)

•CH3 •CH2CH3

•

•

Multiple Substituents – Saturation II

-100-90-80

•

•

•

(exp.)


J. M. McBride, „The Hexaphenylethane Riddle“, Tetrahedron 1974, 30, 2009.

The Triphenylmethyl Radical

•

Cl

Ag

CCl4

H

M. Gomberg, „Triphenylmethyl, ein Fall von dreiwerthigem Kohlenstoff“, Ber. Dt. Chem. Ges. 1900, 33, 3150.

-70-60-50-40-30-20-100

RSE(kJ/mol)

•CH3 •CH2CH3

-80

•

HN

NH

O

O

• NH

O

•

HN

O

-23.0 -43.0 -66.0

9.5

-75.5

•

HN

NH

O

O

Multiple Substitution – Synergistic Effects


The Interpretation of Radical Stability

RSE = (kJ/mol)-12.8 -8.9 +13.1•

H FH

•

F FH

•

F FF

•

F FHF FH

H

•CH3 CH4+ +DH298

anomeric effect 1

-53.2 kJ/mol

H FH

H

H FH

H

F FH

H

+

CH4 +

anomeric effect 2

-36.6 kJ/mol

•

H FH

•

H FH

•

F FH

+

+•CH3

The Anomeric Effect

VB Theory

MO Theory

n(F)

s*(C-F)

DHrxn = -53.2 kJ/mol

(exp.: -56.9 kJ/mol)

H FH

H

H FH

H

F FH

H

CH4 ++

F FH

H

F FH

H

F FH

H

F FH

H


Stability of s-Radicals

-100-80-60-40-200+20

RSE(kJ/mol)

•CH3• •

•

+40+60

•

•

HH

H•

O O

•

O NH

•

O H


s-Radicals vs. p-Radicals

RSE(kJ/mol)

•

H

H

H

H

H

-72.0+37.0

MO π1C

CC

HH

H

HH

MO π2

MO π3

CC

C

HH

H

HH

CC

C

HH

H

HH

top view:

C

H

CCH H

H

H

C

H

CCH H

H

H

C

H

CCH H

H

H

MO π1

MO π6

MO π4MO π5

MO π3MO π2

SOMO

•

The Stability of Carbon-Centered Radicals

•NH2 + R2N-H H3N + R2N•DHrxn

•NH2 + CH3NH2 H3N + CH3NH•DHexp =

-33.4 kJ/mol[a]

. . . and the Stability of Nitrogen-Centered Radicals



-17.0 kJ/mol[a]


The Stability of Nitrogen-Centered Radicals

-100-80-60-40-200+20RSE

(kJ/mol)

•NH2

+40+60

O

NH3C

H•

O

NH

H•

HN

H3C

•

•

HN

•N

•

NH2HN


DPPH - A Persistent Nitrogen-Centered Radical

•

N N

O2N

O2N

NO2

1,1-Diphenyl-2-picrylhydrazyl (DPPH)

• stable solid with mp = 130 oC

• EPR standard at g = 2.0036

• radical trap


•SH + RS-H H2S + RS•DHrxn

•SH + CH3SH H2S + CH3S•DHexp =

-15.5 kJ/mol

. . . and the Stability of Sulfur-Centered Radicals



-17.0 kJ/mol[a]

The Stability of Sulfur-Centered Radicals

-30-20-100RSE

(kJ/mol)

•SH

-40

•S-CH3•

HN

NH

O

OS

•

NH2H2N

O

S

•S

•S-C(CH3)3


•OH + RO-H H2O + RO•DHrxn

•OH + CH3OH H2O + CH3O•DHexp =

-56.9 kJ/mol[a]

…. and the Stability of Oxygen-Centered Radicals





-17.0 kJ/mol[a]

The Stability of Oxygen-Centered Radicals

-180-120-600

RSE(kJ/mol)•OH

DH298(G3B3-D3) [kJ/mol]

-240

O•

O • O•O•

OO•OH O•

NO•

TEMPO - A Persistent Oxygen-Centered Radical

(2,2,6,6-Tetramethylpiperidin-1-yl)oxyl (TEMPO)

• stable solid with mp = 36 oC• mediator for living radical polymerization

• radical trap

•

O N

•

O N

• catalyst for oxidation reactions

•OH

0 -20 -40 -60 -80 -100 -120 -140

•O

0 -20 -40 -60 -80 -100+20

•CH3

HN

NH

O

•O

0 -20 -40+20

•SH

500 480 460 440 420 400 380 360

BDE(X-H) [kJ/mol]

RSE (RO-H)

RSE (R3C-H)

RSE (RS-H)

O

OH OH

N

NN

N

NH2

•

340

•O

S CH3•

HN

NH

O

S•O

•CH2CH3

••

•

320

+40

-160

•

•S

•O

HN

NH

O

O

O•

Matching Radical-Stability Scales

(+497.3)

(+439.0)

(+381.2)

anchorpoint

HSnBu3

(+326.4)

-70-60-50-40-30-20-100

RSE(kJ/mol)

•CH3 •CH2CH3

-80

•

HN

NH

O

O

• NH

O

•

HN

O

(-23.0)(-43.0) (-75.5)

Calculating Bond Dissociation Energies (BDE)

BDE(R-H) = BDE(CH3-H) + RSE(R•)

BDE(Gly-H) = +439.0 -75.5 = +363.5 kJ/mol

BDE(C-H) = +439.0


•OH

0 -20 -40 -60 -80 -100 -120 -140

•O

0 -20 -40 -60 -80 -100+20

•CH3

HN

NH

O

•O

0 -20 -40+20

•SH

500 480 460 440 420 400 380 360

BDE(X-H) [kJ/mol]

RSE (RO-H)

RSE (R3C-H)

RSE (RS-H)

O

OH OH

N

NN

N

NH2

•

340

•O

S CH3•

HN

NH

O

S•O

•CH2CH3

••

•

320

+40

-160

•

•S

•O

HN

NH

O

O

O•


(+497.3)

(+439.0)

(+381.2)

anchorpoint

HSnBu3

(+326.4)

Calculating Hydrogen-Transfer Reaction Energies

•R1 + R2-H R1-H + R2•DHrxn

DHrxn = BDE(R2-H) – BDE(R1-H)

•

+OMe

H

+OMe

•

H

DHrxn

DHrxn = BDE((CH3O)(CH3)2C-H) - BDE(Ph-H)


-100-80-60-40-200+20

RSE(kJ/mol)•CH3

•

+40+60

•


OMe

•

340360380400420440460480500

BDE (X-H)(kJ/mol)

(+37.0)(-36.6)

BDE(C-H) = +439.0

BDE(Ph-H) = +476.0

BDE((CH3O)(CH3)2C-H) = +402.4

DHrxn =

- 73.6 kJ/mol



•R1 + R2-H R1-H + R2•DHrxn

DHrxn = BDE(R2-H) – BDE(R1-H)

•

+OMe

H

+OMe

•

H

DHrxn

DHrxn = BDE((CH3O)(CH3)2C-H) - BDE(Ph-H)

DHrxn = 402.4 - 476.0 = -73.6 kJ/mol


Protecting Group/Radical Translocating (PRT) ReactionsD. P. Curran et al., J. Am. Chem. Soc. 1988, 110, 5900.

AIBN

HSnBu3 54%

O

I

CO2Et

O

CO2Et

H

•SnBu3

O

CO2Et

•H

1,5-HO

CO2Et

•H


-100-80-60-40-200+20

RSE(kJ/mol)

•CH3

-100-80-60-40-200+20+40

340360380400420440460480500

BDE (X-H)

H-SnBu3

(kJ/mol)

•

•

•

OEt

O

•

OMe

•

OO

•H H

H

•


Protecting Group/Radical Translocating (PRT) Reactions

AIBN

HSnBu3 54%

•SnBu3

1,5-H

O

I

CO2Et

O

CO2Et

H

O

CO2Et

•H

O

CO2Et

•H

1,5-exoO

CO2Et

•

HSnBu3

D. P. Curran et al., J. Am. Chem. Soc. 1988, 110, 5900.


-100-80-60-40-200+20

RSE(kJ/mol)

•CH3

-100-80-60-40-200+20+40

340360380400420440460480500

BDE (X-H)

H-SnBu3

(kJ/mol)

•

•

•

OEt

O

•

OMe

•

OO

•H H

H

•



AIBN

HSnBu3 54%

•SnBu3

1,5-H

O

I

CO2Et

O

CO2Et

H

O

CO2Et

•H

O

CO2Et

•H

1,5-exoO

CO2Et

•

HSnBu3



AIBN

HSnBu3 54%

•SnBu3

1,5-H

O

I

CO2Et

O

CO2Et

H

O

CO2Et

•H

O

CO2Et

•H

1,5-exoO

CO2Et

•

HSnBu3


32%

HSnBu3 O

CO2EtH


-100-80-60-40-200+20

RSE(kJ/mol)

•CH3

-100-80-60-40-200+20+40

340360380400420440460480500

BDE (X-H)

H-SnBu3

(kJ/mol)

•

•

•

OEt

O

•

OMe

•

OO

•H H

H

•



AIBN

HSnBu3 54%

•SnBu3

1,5-H

O

I

CO2Et

O

CO2Et

H

O

CO2Et

•H

O

CO2Et

•H

1,5-exoO

CO2Et

•

HSnBu3


32%

HSnBu3 O

CO2EtH

•OH

0 -20 -40 -60 -80 -100 -120 -140

•O

0 -20 -40 -60 -80 -100+20

•CH3

HN

NH

O

•O

0 -20 -40+20

•SH

500 480 460 440 420 400 380 360

BDE(X-H) [kJ/mol]

RSE (RO-H)

RSE (R3C-H)

RSE (RS-H)

O

OH OH

N

NN

N

NH2

•

340

•O

S CH3•

HN

NH

O

S•O

•CH2CH3

••

•

320

+40

-160

•

•S

•O

HN

NH

O

O

O•


(+497.3)

(+439.0)

(+381.2)

anchorpoint

HSnBu3

(+326.4)

Radical Stability – Literature Data

•CH3 + R-H CH4 + R•RSE

J. Hioe, H. Zipse, Faraday Disc. 2010, 145, 301.

M. L. Coote, C. Y. Lin, H. Zipse, p. 83 - 104, in M. D. E. Forbes (Ed.), Carbon-Centered Free Radicals and Radicals Cations, John Wiley & Sons, 2010.

J. Hioe, H. Zipse, Org. Biomol. Chem. 2010, 8, 3609.

J. Hioe, A. Karton, J. M. L . Martin, H. Zipse, Chem. Eur. J. 2010, 16, 6861.Corrigendum: Chem. Eur. J. 2010, 16, 6722.

Y.-R. Luo, Comprehensive Handbook of Chemical Bond Energies, CRC Press, 2007.

J. Hioe, H. Zipse, p. 449 – 476 in Encyclopedia of Radicals in Chemistry,Biology and Materials, C. Chatgilialoglu, A. Studer (eds.), Wiley & Sons, 2012.

J. Hioe, G. Savasci, H. Zipse, Chem. Eur. J. 2011, 17, 3781.

radical stability

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