controlling azobenzene photoswitching through …s2 table of contents: 1. the structures of the...

S1

Supporting information

Controlling azobenzene photoswitching through combined ortho-

fluorination and –amination

Zafar Ahmed+, Antti Siiskonen+, Matti Virkki, Arri Priimagi*

Laboratory of Chemistry and Bioengineering, Tampere University of Technology, P.O. Box

541, FI-33101 Tampere, Finland.

E-mail: [email protected]

ORCID IDs:

Zafar Ahmed: 0000-0002-4737-6238

Antti Siiskonen: 0000-0003-3718-2031

Matti Virkki: 0000-0003-1340-9297

Arri Priimagi: 0000-0002-5945-9671

Electronic Supplementary Material (ESI) for ChemComm.This journal is © The Royal Society of Chemistry 2017

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Table of Contents:

1. The structures of the synthesized compounds 1 – 9 S3

2. General methods S3 – S4

3. Synthetic procedures S3 – S7

4. Computational studies S8 – S18

5. NMR spectra for compounds S19 – S30

6. Mass spectra for compounds S31 – S35

7. Photoisomerization studies S35 – S44

8. References S45

S3

1. The structures of the synthesized compounds 1 – 9

2. General Methods

All commercially available reagents and solvents were purchased either from Sigma Aldrich

Co. or from VWR and were used without further purifications unless otherwise mentioned.

Purification of the products was carried out either by column chromatography on Silica gel 60

(Merck) mesh size 40-63 µm or on preparative TLC plates (Merck) coated with neutral

aluminium oxide 60 F254. NMR spectra were recorded using Varian Mercury 300 MHz

spectrometer using TMS as internal standard. HRMS measurements were done with Waters

LCT Premier XE ESI-TOF bench top mass spectrometer. Lock-mass correction (leucine

enkephaline as reference compound), centering and calibration were applied to the raw data to

obtain accurate mass. UV-visible absorption spectra were recorded using quartz cuvettes on an

S4

Agilent Cary 60 spectrophotometer equipped with an Ocean Optics qpod 2e Peltier-

thermostated cell holder (temperature accuracy ± 0.1 °C). Photoexcitation experiments were

conducted using a Prior Lumen 1600 light source with multiple choices for narrow-band LEDs

at different wavelengths. The photoexcitation wavelengths were chosen for each compound

near an absorption maximum.

3. Synthesis

(E)-1-(2-fluoro-4-methoxyphenyl)-2-(4-methoxyphenyl)diazene (1):

To a solution of 3-fluorophenol (3 mmol, 236 mg) and 4-methoxyphenyldiazonium

tetrafluoroborate (3.3 mmol, 732 mg) in MeCN (7.5 mL) was added K2CO3 (12 mmol, 1.65 g)

at room temperature. The reaction mixture turned reddish-brown. After 30 min, another portion

of K2CO3 (3.0 mmol, 414 mg) and methyl iodide (6 mmol, 360 uL) were added and the mixture

was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate,

filtered through Celite and concentrated on rotary evaporator. The crude was purified by

column chromatography on silica gel using 20% ethyl acetate/hexane to yield compound 1

(600 mg, 77%) as orange-yellow solid. 1H NMR (300 MHz, CDCl3, TMS): δ = 7.90 (d, J =

9.09 Hz, 2H), 7.80-7.74 (m, 1H), 6.99 (d, J = 9.09 Hz, 2H), 6.79-6.73 (m, 2H), 3.89 (s, 3H),

3.87 (s, 3H). 13C NMR (75 MHz, CDCl3, TMS): δ = 162.76, 161.86, 160.99 (d, J = 246.02 Hz),

147.29, 134.98 (d, J = 7.19 Hz), 124.65, 118.49 (d, J = 1.66 Hz), 114.16, 110.67 (d, J = 2.76

Hz), 101.84 (d, J = 23.77 Hz), 55.82, 55.55. 19F NMR (282 MHz, CDCl3): δ = -122.34 (m).

MS (ESI-TOF): m/z calcd for C14H13FN2O2: 261.1101; found: 261.1039 [M+H]+.

(E)-1,2-bis(2-fluoro-4-methoxyphenyl)diazene (2):

Compound 2 was prepared following a reported procedure.[1] A mixture of 2-fluoroaniline

(3.61 mmol, 510 mg), freshly ground KMnO4 (1.80 g) and FeSO4·7H2O (1.80 g) in DCM (36

mL) was refluxed overnight. After cooling to the room temperature, the reaction mixture was

filtered through Celite, dried over MgSO4 and concentrated under reduced pressure. The crude

residue was purified by column chromatography using 20% ethyl acetate/hexane to give the

desired symmetrical azobenzene 3 (350 mg, 35%) as an orange/red solid. 1H NMR (300 MHz,

CDCl3, TMS): δ = 7.84-7.78(m, 2H), 6.79-6.73 (m, 4H), 3.88 (s, 3H). 13C NMR (75 MHz,

CDCl3, TMS): δ = 163.31 (d, J = 9.40 Hz), 161.50 (d, J = 256.52 Hz), 135.49 (d, J = 7.19 Hz),

118.95 (d, J = 2.21 Hz), 111.01 (d, J = 2.77 Hz), 102.04 (d, J = 23.77 Hz), 56.10. 19F NMR

S5

(282 MHz, CDCl3): δ = -122.07 (m). MS (ESI-TOF): m/z calcd for C14H12F2N2O2: 279.0943;

found: 279.0945 [M+H]+.

(E)-1-(2,6-difluoro-4-methoxyphenyl)-2-(4-methoxyphenyl)diazene (3):

Compound 3 was prepared by following the similar procedure used for the synthesis of 1. To

a solution of 3,5-difluorophenol (2 mmol, 262 mg) and 4-methoxyphenyldiazonium

tetrafluoroborate (2.2 mmol, 488 mg) in MeCN (5 mL) was added K2CO3 (8 mmol, 1.10 g) at

room temperature. The reaction mixture turned reddish-brown. After 30 min, another portion

of K2CO3 (2.0 mmol, 276 mg) and methyl iodide (4 mmol, 240 uL) were added and the mixture

was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate,

filtered through Celite and concentrated on rotary evaporator. The crude was purified by

column chromatography on silica gel using 20% ethyl acetate/hexane to yield compound 2

(445 mg, 84%) as orange-yellow solid. 1H NMR (300 MHz, CDCl3, TMS): δ = 7.90 (d, J =

9.00 Hz, 2H) , 7.00 (d, J = 9.00 Hz, 2H), 6.58 (d, J = 9.00 Hz, 2H), 3.90 (s, 3H), 3.86 (s, 3H). 13C NMR (75 MHz, CDCl3, TMS): δ = 162.26, 160.86 (t, J = 13.52 Hz), 157. 20 (dd, J =

257.87, 7.73 Hz), 147.93, 124.56, 114.16, 98.95 (d, J = 2.90 Hz), 98.60 (d, J = 1.93 Hz), 56.00,

55.58. 19F NMR (282 MHz, CDCl3): δ = -118.73 (m). MS (ESI-TOF): m/z calcd for

C14H12F2N2O2: 279.0928; found: 279.0945 [M+H]+.

(E)-1-(5-methoxy-2-((4-methoxyphenyl)diazenyl)phenyl)pyrrolidine (4):

A mixture of compound 1 (0.115 mmol, 30 mg) and pyrrolidine (2 mL) was stirred at room

temperature for 6 hours. The reaction mixture was diluted with ethyl acetate (20 mL). The

organic phase was washed with water (3×), dried over Na2SO4 and concentrated. The crude

was purified over silica gel using ethyl acetate/hexane (20%) as eluent to yield compound 4

(32 mg, 90%) as dark orange solid.1H NMR (300 MHz, CDCl3, TMS): δ = 7.80 (d, J = 9.00

Hz, 1H), 7.75 (d, J = 9.00 Hz, 2H), 6.99 (d, J = 9.00 Hz, 2H), 6.34-6.29 (m, 2H), 3.88 (s, 3H),

3.86 (s, 3H), 3.70-3.26 (m, 4H), 2.03-1.99 (m, 4H). 13C NMR (75 MHz, CDCl3, TMS): δ =

162.52, 160.22, 148.28, 147.86, 135.54, 123.76, 118.22, 114.06, 103.50, 99.39, 55.49, 55.27,

52.42, 25.93. MS (ESI-TOF): m/z calcd for C18H21N3O2: 312.1716; found: 312.1712 [M+H]+.

(E)-1-(5-methoxy-2-((4-methoxyphenyl)diazenyl)phenyl)piperidine (5):

A mixture of compound 1 (0.096 mmol, 25 mg) and pyrrolidine (2 mL) was stirred at 55 ˚C

for 20 hours. The reaction mixture was cooled to room temperature and diluted with ethyl

acetate (20 mL). The organic phase was washed with water (3×), dried over Na2SO4 and

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concentrated. The crude product was purified over silica gel using ethyl acetate/hexane (20%)

as eluent to yield compounds 5 (30 mg, 96 %) as dark orange solid. 1H NMR (300 MHz, CDCl3,

TMS): δ = 7.90 (d, J = 9.00 Hz, 2H) , 7.69 (d, J = 6.00 Hz, 1H), 7.00 (d, J = 9.00 Hz, 2H),

6.59-6.52 (m, 2H), 3.89 (s, 3H), 3.86 (s, 3H), 3.23-3.19 (m, 4H), 1.87-1.79 (m, 4H), 1.68-1.60

(m, 2H). 13C NMR (75 MHz, CDCl3, TMS): δ = 162.65, 161.41, 153.23, 147.79, 139.26,

124.56, 118.28, 114.36, 106.57, 104.50, 55.76, 55.63, 54.74, 26.59, 24.63. MS (ESI-TOF): m/z

calcd for C19H23N3O2: 326.1848; found: 326.1869 [M+H]+.

(E)-1-(2-((2-fluoro-4-methoxyphenyl)diazenyl)-5-methoxyphenyl)pyrrolidine (6): A

mixture of compound 2 (0.089 mmol, 25 mg) and pyrrolidine (2 mL) were stirred at room




(24 mg, 81 %) and 7 (5 mg, 15%) as dark orange solids respectively. 1H NMR (300 MHz,

CDCl3, TMS): δ = 7.85 (d, J = 9.00 Hz, 1H), 7.58-7.52 (m, 1H), 6.78-6.70 (m, 2H), 6.32-6.25

(m, 2H), 3.85 (s, 6H), 3.69-3.64 (m, 4H), 2.03-1.98 (m, 4H). 13C NMR (75 MHz, CDCl3, TMS):

δ = 163.13, 161.29 (d, J = 10.50 Hz), 160.42 (d, J = 252.66 Hz), 148.78, 136.21, 136.05 (d, J =

6.63 Hz), 118.90, 118.80 (d, J = 2.76 Hz), 110.70 (d, J = 3.32 Hz), 104.14, 102.08 (d, J = 23.77

Hz), 99.44, 56.00, 55.52, 52.70, 26.17. 19F NMR (282 MHz, CDCl3): δ = -123.17 (m). MS

(ESI-TOF): m/z calcd for C18H20FN3O2: 330.1602; found: 330.1618 [M+H]+.

(E)-1,2-bis(4-methoxy-2-(pyrrolidin-1-yl)phenyl)diazene (7): A mixture of compound 3

(0.071 mmol, 20 mg) and pyrrolidine (2 mL) was stirred at 55 ˚C for 20 hours. The reaction

mixture was cooled to room temperature and diluted with ethyl acetate (20 mL). The organic

phase was washed with water (3×), dried over Na2SO4 and concentrated. The crude product

was purified over silica gel using ethyl acetate/hexane (20%) as eluent to yield compounds 6

(6 mg, 21 %) and 7 (20 mg, 74%) as dark orange solids. Compound 7: 1H NMR (300 MHz,

CDCl3, TMS): δ = 7.59 (d, J = 9.68 Hz, 2H), 6.34-6.30 (m, 4H), 3.85 (s, 6H), 3.69-3.65 (m,

8H), 2.02-1.98 (m, 8H). 13C NMR (75 MHz, CDCl3, TMS): δ = 161.56, 148.01, 136.71, 118.41,

103.15, 100.00, 55.50, 52.70, 26.16. MS (ESI-TOF): m/z calcd for C22H28N4O2: 381.2296;

found: 381.2291[M+H]+.

(E)-1,1'-(5-methoxy-2-((4-methoxyphenyl)diazenyl)-1,3-phenylene)dipyrrolidine (8): A

mixture of compound 3 (0.093 mmol, 26 mg) and pyrrolidine (2 mL) was stirred at room


S7



(10 mg, 28%) as dark orange solid. The compound 6 was very labile as degradation was already

observed during purification and characterization.1H NMR (300 MHz, CDCl3, TMS): δ = 7.65

(d, J = 8.78 Hz, 2H), 6.5 (d, J = 8.78 Hz, 2H), 5.81 (s, 2H), 3.86 (s, 3H), 3.84 (s, 3H), 3.40-

3.35 (m, 8H), 1.94-190 (m, 8H). 13C NMR (75 MHz, CDCl3, TMS): δ = 162.38, 159.19,

148.87, 148.40, 122.61, 113.97, 113. 86, 88.97 (d, J = 4.61 Hz), 55.52-55.03 (m), 52.42, 25.82.

MS (ESI-TOF): m/z calcd for C22H28N4O2: 381.2263; found: 381.2291[M+H]+.

(E)-1-(3-fluoro-5-methoxy-2-((4-methoxyphenyl)diazenyl)phenyl)pyrrolidine (9):

To a solution of compound 3 (0.2 mmol, 53 mg) in MeCN (2 mL) was added pyrrolidine (1

mmol, 80 uL) dropwise at room temperature. After 2.5 h, the reaction mixture was diluted with

EtOAc (25 mL), washed with saturated NaHCO3 (15 mL), dried over Na2SO4, filtered and

evaporated. The crude was purified over silica gel using 5% ethyl acetate/toluene as eluent to

yield compound 9 (61 mg, 92%) as an orange solid. 1H NMR (300 MHz, CDCl3, TMS): δ =

7.78 (d, J = 9.00 Hz, 2H), 6.99 (d, J = 9.00 Hz, 2H), 6.13-6.03 (m, 2H), 3.88 (s. 3H), 3.82 (s,

3H), 3.51-3.47 (m, 4H), 1.96-1.91 (m, 4H). 13C NMR (75 MHz, CDCl3, TMS): δ = 161.06,

160.61 (d, J = 14.49 Hz), 154.30 (d, J = 256.90), 148.16, 148.09, 148.07 (m), 125.66 (d, J =

7.73 Hz), 123.76, 114.13, 114.04, 95.55 (d, J = 1.93 Hz), 91.39, 91.06, 55.55-55.37 (m), 52.47,

25.82. 19F NMR (282 MHz, CDCl3): δ = -122.05 (m). MS (ESI-TOF): m/z calcd for

C18H20FN3O2: 330.1635; found: 330.1618 [M+H]+.

S8

4. Computational studies

All the calculations were performed with Gaussian 16 Revision A.03 (Gaussian Inc.,

Wallingford CT). The B3LYP/6-31+G(d,p) method was used and the calculations were

performed in acetonitrile using the polarizable continuum model (PCM). Default values were

used for other parameters. A frequency calculation was performed after each geometry

optimization to conform that the obtained conformation was a true minimum (i.e. no imaginary

frequencies) or a transition state (one imaginary frequency). Intrinsic reaction coordinate (IRC)

runs were used to verify that the obtained transition states lead to starting materials and

products.

The density functional theory calculations, used to gain further insight into the reaction

mechanism and selectivity, revealed that the azo group could act either as a base or as a

hydrogen-bond acceptor, thereby leading to two different reaction mechanisms (see below).

Reaction of 1 with piperidine and that of 3 and 9 with pyrrolidine proceeds via three-step

mechanism. The initial transition state leads to an intermediate with the proton still attached to

the amine nitrogen. This proton migrates to the azo group and cleavage of fluorine in the final

step affords the desired product. Compounds 1, 2 and 6 react with pyrrolidine via a one-step

mechanism where the initial transition state directly leads to the final product and the azo group

acts only as a hydrogen-bond acceptor, not as a base. In both mechanisms, the attack by amine

is the rate-determining step. The selectivity can be explained by comparing the energy barriers

for that step (Table S1). As expected, the electron-withdrawing fluorine in 3 clearly decreases

the energy barrier, or increases the reaction rate. The second amination of the resulting product

(9 à 8) is much slower, presumably due to steric hindrance and the electron-donating effect

of the pyrrolidine substituent. A fluorine on the opposite ring, as in 2, does not have a

significant effect on the energy barrier. However, the presence of an amine on the opposite

ring, as in 6, increases the energy barrier significantly, presumably due to steric effects.

S9

Transition states:

The transition states were located using the command “opt(ts,calcfc)” and the starting geometry

for the calculations were chosen by running a constrained geometry scan and varying the

relevant interatomic distance (Figure S1). The geometry with the highest energy was chosen as

the starting geometry. The scan A was used to locate the starting geometry for the first reaction

step, B for the proton transfer step and C for the fluorine cleavage step.

Figure S1. Constrained geometry scans. The interatomic distance that is varied is marked with

r(x-x).

N

NF

N H

r(C-N)

N

N-

F N+H

r(N-H)

N

HN

F Nr(C-F)

A B

C

Table S1. The amination reaction energy barriers (∆E) and changes in free energies (∆G) for the transition states (in kcal mol-1) (B3LYP/6-31+G(d,p)) in acetonitrile (PCM).

Reaction ∆E[a] ∆E relative to 1 à 4

∆G[a] ∆G relative to 1 à 4

1 à 4 17.0 0 32.9 0 1 à 5 24.1 7.1 39.3 6.4

2 à 6 17.3 0.3 33.2 0.3 6 à 7 22.6 5.6 36.6 3.7 3 à 9 15.2 -1.8 30.9 -2.0 9 à 8 20.1 3.1 34.4 1.5 [a] Relative to the sum of starting materials

S10

One-step vs three-step mechanism:

The proposed one-step (starting material à product) and three-step reaction (starting material

à intermediate 1 à intermediate 2 à product) mechanisms are shown in Figure S2.

Figure S2. Proposed reaction mechanisms of the amination reaction.

In the one-step mechanism, the first transition state leads directly to the final product by

fluorine cleavage. In that case, the azo group functions as a coordinating group via a hydrogen

bond, not as a base.

In the three-step mechanism, the first transition state leads to the intermediate 1 where the

proton is still attached to pyrrolidine. The proton is then transferred to the azo group via another

transition state with a very low energy barrier. The fluorine cleavage then proceeds via a third

transition state, which also has a low energy barrier. Finally, the azo group is (presumably)

deprotonated by excess pyrrolidine to afford the final product (that step was not modelled)

N

N

F NH

N

N-

F N+

N

N

N

C-F cleavage

H

protontransfer

N

HN

F N

1) C-F cleavage2) proton removal

rate-determining transition state intermediate 1

intermediate 2final product

S11

Transition states and intermediates for the amination of 1-3, 6 and 9:

Reaction 1 à 4: The amination reaction of compound 1 with pyrrolidine proceeds in one-step.

The transition state geometry is shown in Figure S3. The IRC run from that transition state led

to a geometry similar to intermediate 1 but the subsequent geometry optimization led to the

final product, not intermediate 1. The transition state for the proton transfer could be located

by starting the constrained geometry optimization from the intermediate 2 (not from the

intermediate 1 as for other compounds) but the IRC run backwards from that transition state,

which should lead to the intermediate 1, leads to the final product. This odd behavior might be

explained by a bifurcated transition state but that idea was not further studied.

Figure S3. Reaction 1 à 4: transition state geometry.

Reaction 1 à 5: The amination reaction of 1 with piperidine proceeds in three steps. The

transition state for the first step is shown in Figure S4 and the energy barrier is +24.1 kcal/mol.

The intermediate 1 is shown in Figure S5 and the energy is +13.0 kcal/mol compared to the

starting materials. The transition state for the proton transfer is shown in Figure S6 and the

energy is +8.1 kcal/mol. The intermediate 2 is shown in Figure S7 and the energy is +6.2

kcal/mol compared to the starting materials. The transition state for the final step, or the

fluorine cleavage is shown in Figure S8 and the energy barrier is +4.1 kcal/mol.

S12

Figure S4. Reaction 1 à 5: transition state geometry for the first step.

Figure S5. Reaction 1 à 5: optimized geometry of the intermediate 1.

Figure S6. Reaction 1 à 5: transition state geometry for the proton transfer step.

S13


Figure S8. Reaction 1 à 5: transition state geometry for the fluorine cleavage step.

Reaction 2 à 6: The amination reaction of 2 proceeds in one step. The transition state is shown

in Figure S9 and the energy barrier for that step is +17.0 kcal/mol. The IRC run forward of this

transition state leads directly to the final product by cleavage of the fluorine and without the

transfer of the proton. Therefore, in this case the azo group acts only as a hydrogen bond

acceptor, not as a base.

S14


Reaction 6 à 7: The amination reaction of 6 proceeds in one-step. The transition state is shown

in Figure S10 the energy barrier is +22.6 kcal/mol. The IRC run forward of that transition state

leads directly to the final product without the proton transfer. Therefore, in this case the azo

group acts only as a hydrogen bond acceptor, not as a base.


S15

Reaction 3 à 9: The amination reaction of 3 proceeds in three steps. The transition state for

the first step is shown in Figure S11 and the energy barrier is 15.2 kcal/mol. The intermediate

1 is shown in Figure S12 and the energy is +9.1 kcal/mol compared to starting materials. The

transition state for the proton transfer step is shown in Figure S13 and the energy barrier is only

2.4 kcal/mol. The intermediate 2 is shown in Figure S14 and the energy is +3.9 kcal/mol

compared to the starting materials. The transition state for the final step, or fluorine cleavage,

is shown in Figure S15. The energy barrier for that step is 4.7 kcal/mol.



S16




S17

Reaction 9 à 8: The amination reaction of 9 proceeds in three steps. The transition state for

the first step is shown in Figure S16 and the energy barrier is +20.1 kcal/mol. The intermediate

1 is shown in Figure S17 and the energy is +13.6 kcal/mol compared to the starting materials.

The transition state for the proton transfer is shown in Figure S18 and the energy barrier is only

+1.2 kcal/mol. The intermediate 1 is shown in Figure S19 and the energy is +6.0 kcal/mol

compared to the starting materials. The transition state for the final step, or the fluorine

cleavage, is shown in Figure S20 and the energy barrier is only +1.9 kcal/mol.



S18




S19

5. NMR spectra

Compound 1

Chemical Shift (ppm)8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0

Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

2.90

2.18

2.36

1.00

2.12

7.92 7.

897.

787.

74

7.26

7.01

6.98

6.78

6.76 6.

74 6.74

3.89

3.87

Chemical Shift (ppm)168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24

Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

1.6

1.7

162.

7616

1.86

159.

36

147.

29

135.

0313

4.94

124.

65

118.

48

114.

1611

0.69

110.

65

102.

0010

1.69

77.4

377

.00

76.5

8

55.8

255

.55

S20

Compound 2

Chemical Shift (ppm)-32 -40 -48 -56 -64 -72 -80 -88 -96 -104 -112 -120 -128 -136 -144 -152 -160 -168 -176

Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

1.6

1.7

-122

.34

-122

.38

Chemical Shift (ppm)-122.1 -122.2 -122.3 -122.4 -122.5 -122.6

-122

.31

-122

.34

-122

.35

-122

.38

Chemical Shift (ppm)9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0

Nor

mal

ized

Inte

nsity

0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

6.02

4.32

2.00

7.84

7.81

7.78

7.26 6.

796.

786.

746.

73

3.88

S21

Chemical Shift (ppm)176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24

Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.416

3.38 163.

25

159.

84

135.

5413

5.44

122.

79

118.

94

110.

9911

0.16

102.

5010

2.20

101.

89

77.6

677

.25

76.8

2

56.1

0

Chemical Shift (ppm)-32 -40 -48 -56 -64 -72 -80 -88 -96 -104 -112 -120 -128 -136 -144 -152 -160 -168 -176 -184 -192 -200 -208

Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

-122

.06

Chemical Shift (ppm)-121.5 -122.0

-122

.03

-122

.06

-122

.11

S22

Compound 3


Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

3.20

1.96

2.13

2.00

7.92

7.89

7.27

7.02 6.

99

6.61

6.60

6.57

6.56

3.90

3.86

S23

Compound 4


Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

4.22

4.15

6.00

1.95

1.92

2.81

*

*

7.82 7.79

7.77

7.74

7.27 7.

016.

98

6.34 6.

33 6.30 6.

296.

29

3.88

3.86

3.70

3.68

3.67 3.

66

2.03

2.01

2.00

1.99

S24

Compound 5


Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.416

2.52

160.

22

148.

2814

7.86

135.

54

123.

76

118.

22

114.

06

103.

50 99.3

9

77.4

377

.00

76.5

7

55.4

952

.42 25

.93


Abso

lute

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

1.6

1.7

1.8

8.6

4.4

6.2

2.3

2.2

1.0

2.1

7.92 7.89

7.70

7.68

7.27

7.02

6.99

6.59 6.

596.

566.

55 6.53

6.52

3.89

3.86

3.23 3.21

3.19

1.87 1.

85 1.83

1.81

1.79

1.68 1.

661.

641.

60

S25

Compound 6

Chemical Shift (ppm)168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24

Abso

lute

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

1.6

1.7

1.816

2.65

161.

41

153.

23

147.

79

139.

26

124.

56

118.

2811

4.36

106.

5710

4.50

77.6

977

.26

76.8

4

55.7

6 55.6

354

.74

26.5

924

.63


Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

4.50

4.53

6.46

2.33

2.26

1.12

1.00

*

7.87

7.84

7.58 7.

557.

557.

53 7.52 7.26

6.78 6.77

6.73

6.73

6.32 6.32 6.29 6.

266.

25

3.85

3.69

3.66

3.64

2.03 2.01

2.00

1.99

1.98

S26


Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

1.6

1.716

3.13

162.

1116

1.36

161.

2215

8.73 14

8.78

136.

2113

6.10

136.

01

118.

9011

8.82

110.

72

104.

1410

2.24

101.

9399

.44

77.6

977

.26

76.8

4

56.0

055

.52

52.7

0

26.1

7

Chemical Shift (ppm)-40 -48 -56 -64 -72 -80 -88 -96 -104 -112 -120 -128 -136 -144 -152 -160 -168 -176 -184

Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

-123

.17

Chemical Shift (ppm)-122.7 -122.8 -122.9 -123.0 -123.1 -123.2 -123.3 -123.4

-123

.14

-123

.17

-123

.18

-123

.21

S27

Compound 7


Nor

mal

ized

Inte

nsity

0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

8.09

8.16

5.80

4.16

2.04

7.61 7.57

7.27 6.

346.

336.

326.

326.

30

6.30

3.85

3.69

3.67

3.66

3.65 2.

02 2.01

2.00

1.99

1.98


Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

161.

56

148.

01

136.

71

118.

41

103.

1510

0.00

77.6

977

.26

76.8

4

55.5

052

.70

26.1

6

S28

Compound 8


Nor

mal

ized

Inte

nsity

0

0.5

1.0

1.5

2.0

2.5

3.0

8.83

8.28

6.28

2.00

2.39

1.98

7.66 7.

63

7.27

6.97

6.94

5.81

3.86

3.84

3.38

1.92


Abso

lute

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

1.6

1.7

1.8

162.

3815

9.19

148.

8714

8.40

122.

61

113.

9711

3.86

89.0

088

.94

77.4

377

.00

76.5

7

55.6

155

.52

55.4

255

.33

52.4

2

25.8

2

S29

Compound 9


Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

4.24

4.40

3.29

2.09

2.14

2.00

*

**

7.80

7.78

7.27

7.01

6.98

6.13

6.12

6.10

6.09

6.08

3.88

3.82

3.51

3.49

3.47

1.96 1.

941.

941.

931.

91


Nor

mal

ized

Inte

nsity

0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

161.

0616

0.71

160.

5115

6.01

152.

60

148.

0914

8.07

125.

7112

5.61

123.

76

114.

13 114.

04 95.5

7

91.3

991

.06

77.4

277

.00

76.5

8

55.4

955

.45

55.3

752

.47

25.8

2

S30

Chemical Shift (ppm)0 -8 -16 -24 -32 -40 -48 -56 -64 -72 -80 -88 -96 -104 -112 -120 -128 -136 -144 -152 -160 -168 -176

Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

1.6

1.7

1.8

1.9

2.0

2.1

-122

.05

Chemical Shift (ppm)-121.6 -121.7 -121.8 -121.9 -122.0 -122.1 -122.2 -122.3

-122

.00

-122

.05

-122

.06

S31

6. Mass spectra

Compound 1

Compound 2

clf/MeOH

m/z220 230 240 250 260 270 280 290 300 310 320 330 340 350 360 370 380 390 400 410 420 430 440

%

0

100

%

0

100

%

0

100ZA234 (0.036) Is (1.00,1.00) C14H13FN2O2 1: TOF MS ES+

8.45e12261.1039

262.1071

263.1097

ZA234 1 (0.036) AM (Cen,4, 80.00, Ar,12000.0,557.28,1.00,LS 5); Sm (SG, 2x10.00) 1: TOF MS ES+ 1.10e3261.1101

254.0310222.0036

246.0629223.9997 317.0345265.9420 310.1271282.0288

268.0480 303.0202368.0481

324.0178343.0614 364.0937

413.2720372.1847 399.1189 442.2786435.2975

ZA234 1 (0.036) 1: TOF MS ES+ 181261.1093

254.0303222.0066

223.9941246.0888

310.1251265.9374282.0272 289.0379

317.0270368.0401

323.0434 343.0522 364.9349413.2704399.1173372.1736 442.2660436.2876

M o le c u la r F o rm u la : C 1 4 H 1 3 F N 2 O 2

F o rm u la W e ig h t : 2 6 0 .2 6 3 6 2 3 2

NN

F

O

O

MeCN

m/z245 250 255 260 265 270 275 280 285 290 295 300 305 310 315 320 325 330 335 340 345 350 355

%

0

100

%

0

100

%

0

100ZA275 (0.036) Is (1.00,1.00) C14H12F2N2O2 1: TOF MS ES+

8.45e12279.0945

280.0976

281.1003


249.9836 278.0867264.0720252.1654

280.0981307.2113

281.1047290.2179 295.0949 345.1162309.2214 324.2441 339.1974331.3290 348.2432

ZA275 1 (0.036) 1: TOF MS ES+ 468279.0849

249.9777 278.0779280.0937

307.2015 345.0993

NN

F

O

OF

S32

Compound 3

Compound 4

MeCN

m/z240 245 250 255 260 265 270 275 280 285 290 295 300 305 310 315 320 325 330

%

0

100

%

0

100

%

0

100ASB11 (0.036) Is (1.00,1.00) C14H12F2N2O2 1: TOF MS ES+

8.45e12279.0945

280.0976

281.1003

ASB11 1 (0.036) AM (Cen,4, 80.00, Ar,9000.0,556.28,1.00,LS 5); Sm (SG, 2x10.00) 1: TOF MS ES+ 3.45e3279.0928

249.9827242.0846 244.1017

278.0872250.9865 271.1785259.1624 269.2132

307.2077

280.0964306.2469295.0898281.0977 293.1075

308.2126324.2432322.1458 326.2859

ASB11 1 (0.036) 1: TOF MS ES+ 429279.0858

249.9743242.0764 278.0744

307.2071280.0901

295.0716 306.2524308.2097

324.2444

Acc=6ppmM+1

NN

F

FO

O

Molecular Formula: C14H12F2N2O2Formula Weight: 278.2540864

clf/MeOH

m/z220 230 240 250 260 270 280 290 300 310 320 330 340 350 360 370 380 390 400 410 420 430

%

0

100

%

0

100

%

0

100ZA265 (0.036) Is (1.00,1.00) C18H21N3O2 1: TOF MS ES+

8.04e12312.1712

313.1743

314.1770

ZA265 1 (0.036) AM (Cen,4, 80.00, Ar,9000.0,557.28,1.00,LS 5); Sm (SG, 2x10.00) 1: TOF MS ES+ 992312.1716

310.1558286.1060277.0990

245.0783229.1418 264.1200 309.1312287.1109

313.1740

342.1730319.1981 335.1404 393.2122349.1909 375.1766 413.2870 419.3087

429.1893

ZA265 1 (0.036) 1: TOF MS ES+ 189312.1928

286.1246277.1192

245.0990229.1564 264.1389

310.1762

287.1281 309.1518

313.1942

342.2062318.2061

M o le c u la r F o rm u la : C 1 8 H 2 1 N 3 O 2F o rm u la W e ig h t : 3 1 1 .3 7 8 2 4

N N

O

O N

Acc= 1ppm

S33

Compound 5

Compound 6

Clf/MeOH

m/z290 295 300 305 310 315 320 325 330 335 340 345 350 355 360 365 370 375 380 385

%

0

100

%

0

100

%

0


7.95e12326.1869

327.1899

328.1927


321.2269307.1975301.1507288.1534 299.1776 309.1317

327.1895

331.1748 371.3142349.1720345.2306337.2610 363.2352361.2171 377.2458 381.3541

ZA277 1 (0.035) 1: TOF MS ES+ 794326.1691

321.2230

327.1782

331.1676371.3090348.1612

M o le c u la r F o rm u la : C 1 9 H 2 3 N 3 O 2

F o rm u la W e ig h t : 3 2 5 .4 0 4 8 2

NN

MeO

OMeN

MeCN

m/z290 295 300 305 310 315 320 325 330 335 340 345 350 355 360 365 370 375 380 385

%

0

100

%

0

100

%

0

100ZA276A (0.036) Is (1.00,1.00) C18H20FN3O2 1: TOF MS ES+

8.04e12330.1618

331.1649

332.1676

ZA276A 1 (0.036) AM (Cen,4, 80.00, Ar,9000.0,556.28,1.00,LS 5); Sm (SG, 2x10.00) 1: TOF MS ES+ 948330.1602

287.2561324.2926307.2074296.2562 298.2738 312.2993 321.2316

331.1637

371.3190332.1831 339.3206 369.1751345.1310 358.2137 377.3009 381.3698386.2821

ZA276A 1 (0.036) 1: TOF MS ES+ 117330.1590

287.2509324.2860307.2061296.2537 302.1763 315.2912

331.1646

331.1791 371.3164 377.3059

M+1Acc=4ppm

NN

O

OFN

Molecular Formula: C18H20FN3O2

Formula Weight: 329.3687032

S34

Compound 7

Compound 8

clf/MeOH

m/z364 366 368 370 372 374 376 378 380 382 384 386 388 390 392 394 396 398 400 402 404 406 408

%

0

100

%

0

100

%

0

100ZA279B_gud (0.035) Is (1.00,1.00) C22H28N4O2 1: TOF MS ES+

7.66e12381.2291

382.2321

383.2350

ZA279B_gud 1 (0.035) AM (Cen,4, 80.00, Ar,9000.0,556.28,1.00,LS 5); Sm (SG, 2x10.00) 1: TOF MS ES+ 1.59e3381.2296

369.3534367.3615365.3331

371.3198 380.2259377.3341

391.2870382.2340

383.3621 385.3471389.2996

392.2890397.3808 399.3410

407.4001403.3289

ZA279B_gud 1 (0.035) 1: TOF MS ES+ 162381.2191

369.3272367.3517363.3158

371.3182 380.2174377.3387

391.2816382.2272

383.3713 385.3167387.3711

392.2872

395.2381 397.3874399.3362 405.3496

M+1Acc=1ppm

NN

O

ON

N

Molecular Formula: C22H28N4O2Formula Weight: 380.48332

clf/MeOH

m/z300 320 340 360 380 400 420 440 460 480 500 520 540 560 580 600 620 640 660 680 700 720 740

%

0

100

%

0

100

%

0


7.66e12381.2291

382.2321

383.2350


379.2121

312.2051 338.3428 377.0651

382.2325

419.3192383.2344 427.3800 663.4522513.1722499.1591451.0456 553.2651 634.3146562.0737 597.1015 741.1951679.4380

716.7794

ZA268 1 (0.036) 1: TOF MS ES+ 150381.2479

379.2407

312.2321 339.3747

382.2612

419.3506386.0681 513.2025427.4142 499.1942 663.5166 741.2533

N N

O

O N

N

Molecular Formula: C22H28N4O2Formula Weight: 380.48332

S35

Compound 9

7. Photoisomerization studies

UV–visible absorption spectra were recorded using 1 cm quartz cuvettes on an Agilent

Cary 60 spectrophotometer equipped with an Ocean Optics qpod 2e Peltier-thermostated

cell holder (temperature accuracy ± 0.1 °C). Photoexcitation experiments were performed

using a Prior Lumen 1600 light source with multiple choices for narrow-band LEDs at

different wavelengths. The photoexcitation wavelength was chosen for each compound

near an absorption maximum. The power density was about 250 mW cm-2 and the samples

were illuminated for 30–90 seconds until a photostationary state was reached. All

measurements were done in spectrophotometric grade acetonitrile.

The measurements for compounds 1–3, 5 and 9 were carried out at 50, 60 and 70 ºC due to

their cis-lifetimes being impractically long for a direct measurement at 25 ºC. UV–visible

spectra were measured with time intervals chosen such that around ten points are measured

while the absorbance is seen to return by at least 80 % towards the dark-adapted value after

photoexcitation. The cis-isomer decay was studied by observing the absorbance at a

wavelength chosen on the long-wavelength edge (about 80 % of maximum absorption) of

MeCN

m/z305 310 315 320 325 330 335 340 345 350 355 360 365 370

%

0

100

%

0

100

%

0

100ASB113 (0.035) Is (1.00,1.00) C18H20FN3O2 1: TOF MS ES+

8.04e12330.1618

331.1649

332.1676

ASB113 1 (0.035) AM (Cen,4, 80.00, Ar,9000.0,556.28,1.00,LS 5); Sm (SG, 2x10.00) 1: TOF MS ES+ 900330.1635

307.2117

308.2158 329.1577324.2821321.2005311.0998

331.1674

368.1563365.2000332.1688 341.1922 353.3596348.2394346.1365 362.1669371.3200

ASB113 1 (0.035) 1: TOF MS ES+ 109330.1530

307.2001

308.2073329.1441325.2767321.1808315.2852314.1493

331.1634

365.1916332.1513353.3755337.9683 341.1815 362.1640 368.1354

NN

FO

ON

S36

the longest-wavelength absorption peak clearly visible in the trans-rich absorption

spectrum.

Single exponential fits where performed to determine the cis lifetime at each temperature.

The fitting equation2 was −(𝐴$%& − 𝐴')×𝑒+,- + 𝐴$%&, where 𝐴$%& is the absorbance after

infinite time i.e. absorbance in dark, 𝐴' is the absorbance at the beginning of cis decay, i.e.

absorbance at photostationary state, k it the cis-decay rate constant and t is time. The

parameters 𝐴$%&, 𝐴' and 𝑘 were used as free parameters in the fits. The cis-lifetimes were

then calculated as 𝜏 = 2, where necessary. The natural logarithm of 𝑘 was calculated at

each temperature and plotted as a function of inverse temperature. From these Arrhenius

plots, the cis-lifetimes at 25 ºC were extracted by linear fitting and extrapolation. Error

estimates were extracted from the Arrhenius plots by calculating the maximum and

minimum values for the lifetimes given by the error limits of the Arrhenius plot

extrapolation. The error estimate given is the maximum minus minimum divided by two.

Compounds 4, 6 and 7 were measured at 25 ºC. The values reported for compounds 6 and

7 were measured at the same time of the year. Repetition of the measurement after a few

months for 6 and 7 gave notably shorter lifetime values from same synthetic batch. This

variation might be due to moisture and a varying humidity level at different times of the

year. Compounds 4 and 7 were studied by continuously monitoring the absorbance at a

selected wavelength and compound 6 by measuring the absorption spectrum with chosen

intervals. A Single exponential function mathematically identical to the one used for

compounds 1–3, 5 and 9 was used to determine the cis lifetimes directly from these

measurements and the standard error given by fitting was used for the error estimate.

S37

Figure S21. Thermal cis-to-trans isomerization of compound 1 at 70°C.

Figure S22. Arrhenius plot of compound 1.

S38



S39



S40

Figure S27. Cis-lifetime for compound 4 in kinetic mode at 25°C.

Figure S28. Back and forth switching cycles of 4 using 435 and 595 nm wavelengths.

S41



S42


Figure S32. Cis-lifetime calculation for compound 6.

S43

Figure S33. Cis-lifetime study for compound 7 in kinetic mode at 25°C.


S44


Figure S36. Back and forth switching cycles of 9 using 405 and 595 nm wavelengths.

S45

Figure S37. 1HNMR spectra of compound 9 (expanded methoxy regions) before (a) and after

(b) irradiation with 405 nm. Integration of methoxy protons indicates > 80% trans-cis

conversion.

8. References [1] C.Knie,M.Utecht,F.Zhao,H.Kulla,S.Kovalenko,A.M.Brouwer,P.Saalfrank,S.Hecht,

D.Bleger,Chem.-Eur.J.2014,20,16492.

[2]M.Poutanen,O.Ikkala,A.Priimagi,Macromolecules2016,49,4095.

controlling azobenzene photoswitching through …s2 table of contents: 1. the structures of the...

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