Kinetics of the Diaza-Cope Rearrangement
1
2c: yellow solid in a quantitative yield; mp 196-198 °C; H
rearrangement reaction. The Hammett plot shows that there
is a significant electronic effect for the reaction with a F value
of 1.6. DFT computation reveals that the rearrangement
reaction becomes thermodynamically more favorable for
substrates with electron withdrawing substituents. The di-
imine substrate with a nitro substitutent (1a) rearranges about
50 times faster (∆∆Gq ) -2.3 kcal/mol) than the one with
a methoxy substituent (1g) at room temperature. In addition,
the electronic effect measured from the experimental kinetic
barriers is about half of the electronic effect determined from
the computed thermodynamic barriers in accord with the
Marcus equation. It is interesting that the experimental kinetic
data and the DFT computational thermodynamic data can be
combined in a meaningful way to confirm that the Marcus
equation is applicable in this reaction. An in-depth under-
standing of the electronic effects on the rate and equilibrium
for the rearrangement reaction should be useful for the
synthesis of a wide range of diamines.
NMR (DMSO-d6, 300 MHz, TMS) δ 12.91 (br, 2H), 8.51 (s,
2H), 7.91 (d, J ) 8.1 Hz, 4H), 7.46 (d, J ) 8.1 Hz, 4H),
7.34-7.30 (m, 4H), 6.88-6.86 (m, 4H), 5.24 (s, 2H), 3.83 (s,
6H); 13C NMR (DMSO-d6, 75 MHz) δ 167.4, 166.4, 160.5,
145.5, 133.3, 132.4, 129.6, 129.3, 128.8, 119.4, 119.0, 116.9,
77.5, 52.6; MS (ESI, positive, MeOH) m/z calcd for C32H28N2O6
536.19, found [M + H]+ 537.40, [M + Na]+ 559.40; HRMS
(ESI, positive, MeOH) m/z calcd for C32H29N2O6 [M + H]+
537.2020, found [M + H]+ 537.2026.
1d: white solid in 80% yield; 1H NMR (DMSO-d6, 300 MHz,
TMS) δ 9.76 (br, 2H), 8.13 (s, 2H), 7.66 (d, J ) 8.4 Hz, 4H),
7.49 (d, J ) 8.4 Hz, 4H), 7.23 (d, J ) 6.9 Hz, 2H), 6.99-6.98
(m, 2H), 6.72-6.67 (m, 4H), 5.26 (s, 2H); 13C NMR (DMSO-
d6, 75 MHz) δ 160.8, 155.6, 136.1, 134.9, 130.0, 129.8, 129.3,
128.4, 126.6, 119.0, 115.9, 73.9.
1
2d: yellow solid in a quantitative yield; H NMR (DMSO-d6,
300 MHz, TMS) δ 13.08 (br, 2H), 8.48 (s, 2H), 7.41-7.27 (m,
12H), 6.88-6.86 (m, 4H), 5.11 (s, 2H); 13C NMR (DMSO-d6, 75
MHz) δ 167.1, 160.6, 139.2, 133.3, 132.6, 132.4, 130.2, 128.8,
119.4, 119.0, 116.9, 77.1; MS (ESI, positive, MeOH) m/z calcd
for C28H22Cl2N2O2 488.11, found [M + H]+ 489.30, [M + Na]+
511.30.
Experimental Section
General Procedure for the Synthesis of Compounds 1a-g
and 2a-g. meso-1,2-Bis(2-hydroxylphenyl)ethylenediamine (0.10
mmol) and 2 equiv of p-nitrobenzaldehyde (0.20 mmol) were
dissolved in 2.0 mL of methanol each. And then the two solutions
were mixed and stirred for an hour at room temperature to give
initial diimine 1a as a white precipitate. As a purification process,
the solid was filtered, washed with 0.5 mL of methanol, and
dried under vacuum as a white solid. Temperature dependent
quantitative conversion of 1a to 2a was monitored by a nuclear
magnetic resonance spectroscopy.
1e: white solid in 68% yield; 1H NMR (DMSO-d6, 300 MHz,
TMS) δ 9.59 (br, 2H), 8.15 (s, 2H), 7.65 (d, J ) 7.5 Hz, 4H),
7.44-7.42 (m, 6H), 7.21 (d, J ) 6.9 Hz, 2H), 6.99-6.98 (m,
2H), 6.74-6.65 (m, 4H), 5.26 (s, 2H); 13C NMR (DMSO-d6, 75
MHz) δ 162.1, 155.7, 136.0, 131.5, 129.9, 129.1, 128.4, 128.3,
126.7, 118.9, 116.1, 74.3.
1
2e: yellow solid in a quantitative yield; H NMR (DMSO-d6,
300 MHz, TMS) δ 13.18 (br, 2H), 8.44 (s, 2H), 7.33-7.20 (m,
12H), 6.86-6.83 (m, 6H), 5.07 (s, 2H); 13C NMR (DMSO-d6,
75 MHz) δ 166.7, 160.6, 140.5, 133.1, 132.3, 128.8, 128.4,
128.0, 119.2, 119.0, 116.9, 78.2; MS (ESI, positive, MeOH) m/z
calcd for C28H24N2O2 420.18, found [M + H]+ 421.40, [M +
Na]+ 443.40.
1a: white solid in 70% yield; 1H NMR (DMSO-d6, 300 MHz,
TMS) δ 9.56 (br, 2H), 8.34 (s, 2H), 8.26 (d, J ) 8.7 Hz, 4H),
7.91 (d, J ) 8.7 Hz, 4H), 7.37 (d, J ) 7.2 Hz, 2H), 7.01-6.99
(m, 2H), 6.73-6.71 (m, 4H), 5.42 (s, 2H); 13C NMR (DMSO-
d6, 75 MHz) δ 160.2, 155.6, 149.1, 141.8, 129.7, 129.4, 128.4,
126.5, 124.4, 119.2, 115.8, 73.2.
1f: white solid in 85% yield; mp rearrange to 2f from 143
1
°C, then ends at 198 °C; H NMR (DMSO-d6, 300 MHz, TMS)
1
2a: yellow solid in a quantitative yield; H NMR (DMSO-d6,
δ 10.01 (br, 2H), 8.10 (s, 2H), 7.57 (d, J ) 8.1 Hz, 4H), 7.29
(d, J ) 8.1 Hz, 4H), 7.16 (d, J ) 6.9 Hz, 2H), 6.99-6.98 (m,
2H), 6.73-6.64 (m, 4H), 5.20 (s, 2H), 2.98-2.78 (m, 2H), 1.20
(d, J ) 6.9 Hz, 12H); 13C NMR (DMSO-d6, 75 MHz) δ 161.9,
155.8, 152.2, 133.8, 129.9, 128.6, 128.3, 127.2, 126.7, 118.9,
116.1, 74.6, 33.9, 24.1; HRMS (ESI, positive, MeOH) m/z calcd
for C34H37N2O2 [M + H]+ 505.2849, found [M + H]+ 505.2847
300 MHz, TMS) δ 12.69 (br, 2H), 8.54 (s, 2H), 8.21 (d, J )
8.4 Hz, 4H), 7.62 (d, J ) 8.4 Hz, 4H), 7.38-7.32 (m, 4H),
6.89-6.87 (m, 4H), 5.38 (s, 2H); 13C NMR (DMSO-d6, 75 MHz)
δ 167.8, 160.4, 147.6, 147.4, 133.5, 132.4, 129.8, 124.0, 119.5,
119.0, 117.0, 76.8; MS (ESI, positive, MeOH) m/z calcd for
C28H22N4O6 510.15, found [M + H]+ 511.30, [M + Na]+ 533.30.
1b: white solid in 75% yield; 1H NMR (DMSO-d6, 300 MHz,
TMS) δ 9.59 (br, 2H), 8.24 (s, 2H), 7.89 (d, J ) 8.1 Hz, 4H),
7.81 (d, J ) 8.1 Hz, 4H), 7.31 (d, J ) 7.5 Hz, 2H), 6.99 (t, J )
7.8 Hz, 2H), 6.71-6.69 (m, 4H), 5.37 (s, 2H); 13C NMR (DMSO-
d6, 75 MHz) δ 160.6, 155.6, 140.1, 133.2, 129.7, 129.0, 128.4,
126.6, 119.1, 119.0, 115.8, 113.5, 73.0.
1
2f: yellow solid in a quantitative yield; mp 196-198 °C; H
NMR (DMSO-d6, 300 MHz, TMS) δ 13.23 (br, 2H), 8.38 (s, 2H),
7.29-7.14 (m, 12H), 6.85-6.81 (m, 4H), 4.99 (s, 2H), 2.96-2.76
(m, 2H), 1.14 (d, J ) 6.9 Hz, 12H); 13C NMR (DMSO-d6, 75 MHz)
δ 166.5, 160.6, 148.0, 138.1, 133.0, 132.2, 128.3, 126.7, 119.2,
119.0, 116.8, 77.9, 33.4, 24.3; MS (ESI, positive, MeOH) m/z calcd
for C34H36N2O2 504.28, found [M + H]+ 505.50, [M + Na]+
531.50; HRMS (ESI, positive, MeOH) m/z calcd for C34H37N2O2
[M + H]+ 505.2849, found [M + H]+ 505.2839.
2b: yellow solid in a quantitative yield; 1H NMR (DMSO-d6,
300 MHz, TMS) δ 12.87 (br, 2H), 8.50 (s, 2H), 7.82 (d, J )
8.4 Hz, 4H), 7.51 (d, J ) 8.4 Hz, 4H), 7.39-7.31 (m, 4H),
6.90-6.86 (m, 4H), 5.27 (s, 2H); 13C NMR (DMSO-d6, 75 MHz)
δ 167.7, 160.4, 145.6, 133.5, 132.8, 132.4, 129.4, 119.5, 119.1,
119.0, 117.0, 111.0, 77.1; MS (ESI, positive, MeOH) m/z calcd
for C30H22N4O2 470.17, found [M + H]+ 471.40, [M + Na]+
493.40.
1g: white solid in 74% yield; 1H NMR (DMSO-d6, 300 MHz,
TMS) δ 10.05 (br, 2H), 8.03 (s, 2H), 7.59 (d, J ) 8.1 Hz, 4H),
7.12 (d, J ) 6.9 Hz, 2H), 6.99-6.97 (m, 6H), 6.72-6.61 (m,
4H), 5.13 (s, 2H), 3.78 (s, 6H); 13C NMR (DMSO-d6, 75 MHz)
δ 162.1, 161.4, 155.8, 130.2, 129.9, 128.7, 128.3, 126.8, 118.9,
116.1, 114.6, 74.9, 55.8.
1c: white solid in 80% yield; mp rearrange to 2c from 140
1
°C, then ends at 198 °C; H NMR (DMSO-d6, 300 MHz, TMS)
1
2g: yellow solid in a quantitative yield; H NMR (DMSO-d6,
δ 9.67 (br, 2H), 8.23 (s, 2H), 7.99 (d, J ) 8.1 Hz, 4H), 7.80 (d,
J ) 8.1 Hz, 4H), 7.31 (d, J ) 6.9 Hz, 2H), 6.99-6.98 (m, 2H),
6.72-6.69 (m, 4H), 5.36 (s, 2H), 3.86 (s, 6H); 13C NMR
(DMSO-d6, 75 MHz) δ 166.2, 161.1, 155.6, 140.2, 131.9, 129.9,
129.8, 128.6, 128.4, 126.6, 119.1, 115.9, 74.2, 52.8; HRMS (ESI,
positive, MeOH) m/z calcd for C32H29N2O6 [M + H]+ 537.2020,
found [M + H]+ 537.2009
300 MHz, TMS) δ 13.26 (br, 2H), 8.43 (s, 2H), 7.32-7.23 (m,
8H), 6.89-6.82 (m, 8H), 4.99 (s, 2H), 3.69 (s, 6H); 13C NMR
(DMSO-d6, 75 MHz) δ 166.3, 160.7, 158.9, 133.0, 132.6, 132.2,
129.5, 119.2, 119.1, 116.9, 114.2, 77.5, 55.5; MS (ESI, positive,
MeOH) m/z calcd for C30H28N2O4 480.20, found [M + H]+
481.40, [M + Na]+ 517.50.
J. Org. Chem. Vol. 74, No. 9, 2009 3333