1. General considerations S1

2. Optimization for oxoammonium salt-mediated nitriles synthesis S2

3. Preparation of aldehydes S2

4. General procedures for 4-AcNH-TEMPO+BF4- mediated nitriles synthesis S2

5. Procedure for scale up S7

6. Regeneration of 4-AcNH-TEMPO+BF4- S7

7. References S8

8. 1H and 13C NMR spectra of substrates S9

Supporting Information for

Oxoammonium Salt-Mediated Oxidative Nitriles Synthesisfrom Aldehydes with Ammonium Acetate

Myeong Jin Kima, Junyoung Munb,*, Jinho Kima,*

aDepartment of Chemistry, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 22012, Republic of Korea.

jinho@inu.ac.krbDepartment of Energy and Chemical Engineering, Incheon National University, 119 Academy-ro,

Yeonsu-gu, Incheon 22012, Republic of Korea.jymoon@inu.ac.kr

1. General considerations

All commercially available compounds and solvents were purchased and used as received, unless

otherwise noted. Analytical thin layer chromatography (TLC) was performed on precoated silica gel 60

F254 plates. Visualization on TLC was achieved by the use of UV light (254 nm) and treatment with

phosphomolybdic acid stain followed by heating. Flash chromatography was performed using Silica gel

60 (Merck, particle size 40-63 um, 230-400 mesh). 1H and 13C NMR spectra were recorded on Agilent

400 MHz NMR (Agilent Technologies). Chemical shift values are given in parts per million relative to

internal TMS (0.00 ppm for 1H) or CDCl3 (77.06 ppm for 13C). The following abbreviations were used to

describe peak splitting patterns when appropriate: br = broad, s = singlet, d = doublet, t = triplet, q =

quartet, p = pentet, m = multiplet, dd = double of doublet, dt = double of triplet, td = triple of doublet .

Coupling constants, J, were reported in hertz unit (Hz).

2. Optimization for oxoammonium salt-mediated nitriles synthesis

S1

The oxoammnonium salt, 4-AcNH-TEMPO+BF4-, was synthesized according to known procedure.1

A 15 mm flame-dried test tube, which was equipped with a magnetic stir bar and charged with

oxoammonium salt (2.0 equiv, 0.6 mmol) and NH4X (2.4 equiv, 0.72 mmol), was evacuated and

backfilled with nitrogen (this process was repeated 3 times). After 0.3 mL of solvent was added, octanal

(0.3 mmol), and solvent (0.3 mL) were added in sequence. The reaction mixture was stirred for 12 h at 50 oC under N2 balloon, and then cooled to room temperature. The reaction was diluted by adding EtOAc

and washed 4 M HCl aqueous solution. Two layers were separated, and the aqueous layer was extracted

with EtOAc. The combined organic layers were washed with Na2CO3 aqueous solution. The organic

layer was dried over MgSO4, filtered, and concentrated in vacuo. The 1H NMR yield of desired product

was determined by integration using an internal standard (1,1,2,2-tetrachloroethane).

3. Preparation of aldehydes

6-chlorohexanal was prepared by the oxidation of 6-chlorohexanol.2 Adamantane-1-carbaldehyde, 2-

methyl-2-phenylpropanal, and 4-(tert-butyl)cyclohexanecarbaldehyde were prepared from the

corresponding carboxylic acids.3,4 2-Methyl-3-phenylpropanal was prepared by Heck reaction.5 Other

aldehydes are commercially available.

4. General procedures for 4-AcNH-TEMPO+BF4- mediated nitriles synthesis

A 15 mm flame-dried test tube, which was equipped with a magnetic stir bar and charged with aldehyde

(0.3 mmol, in case of solid), 4-AcNH-TEMPO+BF4- (2.0 equiv, 0.6 mmol), and NH4OAc (4.0 equiv, 1.2

mmol), was evacuated and backfilled with nitrogen (this process was repeated 3 times). After 0.3 mL of

AcOH was added, aldehyde (0.3 mmol, in case of liquid), and AcOH (0.3 mL) were added in sequence.

The reaction mixture was stirred for 12 h at 70 oC under N2 balloon, and then cooled to room temperature.

The reaction was diluted by adding EtOAc and washed 4 M HCl aqueous solution. Two layers were

separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were washed

with Na2CO3 aqueous solution. The organic layer was dried over MgSO4, filtered, and concentrated to a

volume of approximately 20 mL by evaporator. To eliminate remaining aldehyde, aqueous 2 M Na2S2O5

aqueous solution (20 mL) was added to the organic layer and stirred for 2 hours. Two layers were

separated, and the organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue

was purified by column chromatography to give nitrile products.

S2

Octanenitrile6 (Table 2, entry 1); 1H NMR (400 MHz, CDCl3) δ 2.34 (t, J = 7.1 Hz, 2H), δ 1.66 (p, J =

7.4 Hz, 2H), δ 1.44 (p, J = 7.2 Hz, 2H), δ 1.38-1.27 (m, 6H), δ 0.89 (t, J = 6.6 Hz, 3H); 13C NMR (101

MHz, CDCl3) δ 119.8, 31.4, 28.6, 28.4, 25.3, 22.5, 17.1, 14.0.

Decanenitrile3 (Table 2, entry 2); 1H NMR (400 MHz, CDCl3) δ 2.34 (t, J = 7.1 Hz, 2H), δ 1.66 (p, J =

7.3 Hz, 2H), δ 1.45 (p, J = 6.7 Hz, 2H), δ 1.33-1.23 (m, 10H), δ 0.89 (t, J = 6.2 Hz, 3H); 13C NMR (101

MHz, CDCl3) δ 119.4, 31.3, 28.8, 28.7, 28.3, 28.2, 24.9, 22.1, 16.6, 13.6.

6-Chlorohexanenitrile7 (Table 2, entry 3); 1H NMR (400 MHz, CDCl3) δ 3.56 (t, J = 6.5 Hz, 2H), δ

2.38 (t, J = 6.9 Hz, 2H), δ 1.88-1.77 (m, 2H), δ 1.75-67 (m, 2H), δ 1.67-1.59 (m, 2H); 13C NMR (101

MHz, CDCl3) δ 119.4, 44.4, 31.6, 26.0, 24.7, 17.1.

2-Ethylhexanenitrile6 (Table 2, entry 4); 1H NMR (400 MHz, CDCl3) δ 2.50-2.42 (m, 1H), δ 1.69-1.29

(m, 8H), δ 1.08 (t, J = 6.7 Hz, 3H), δ 0.93 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 121.8,

32.8, 31.1, 28.8, 25.1, 21.8, 13.3, 11.1.

Adamantane-1-carbonitrile3 (Table 2, entry 5); 1H NMR (400 MHz, CDCl3) δ 2.07-2.01 (m, 9H), δ

1.76-1.71 (m, 6H); 13C NMR (101 MHz, CDCl3) δ 125.2, 39.9, 35.7, 30.3, 27.0.

2-Methyl-2-phenylpropanenitrile3 (Table 2, entry 7); 1H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 7.4

Hz, 2H), δ 7.34 (t, J = 7.5 Hz, 2H), δ 7.27-7.21 (m, 1H), δ 1.58 (s, 6H); 13C NMR (101 MHz, CDCl3) δ

141.4, 128.9, 127.8, 125.0, 124.5, 37.1, 29.1.

S3

Cyclohexanecarbonitrile6 (Table 2, entry 8); 1H NMR (400 MHz, CDCl3) δ 2.66-2.57 (m 1H), δ 1.91-

1.80 (m, 2H), δ 1.80-1.63 (m, 4H), δ 1.57-1.35 (m, 4H); 13C NMR (101 MHz, CDCl3) δ 122.2, 29.0, 27.5,

24.7, 23.6.

4-tert-Butylcyclohexanecarbonitrile3 (Table 2, entry 9); 1H NMR (400 MHz, CDCl3) Trans : δ 2.31 (tt,

J = 12.5, 3.4 Hz, 1H), δ 2.16 (d, J = 12.7 Hz, 2H), δ 1.85 (d, J = 11.2 Hz, 2H), δ 1.59-1.53 (m, 1H), δ

1.07-0.92 (m, 4H), δ 0.84 (s, 9H) Cis : δ 2.96-2.87 (m, 1H), δ 2.04 (d, J = 13.2 Hz, 2H), δ 1.77 (d, J =

12.9 Hz, 2H), δ 1.53-1.46 (m, 3H), δ 1.44-1.33 (m, 2H), δ 0.87 (s, 9H); 13C NMR (101 MHz, CDCl3)

Trans : δ 123.0, 46.8, 32.4, 30.4, 27.4, 27.3, 23.4 Cis : δ 122.2, 47.6, 32.4, 29.0, 28.4, 27.1, 26.2.

Cyclohex-3-enecarbonitrile8 (Table 2, entry 10); 1H NMR (400 MHz, CDCl3) δ 5.79-5.72 (m, 1H), δ

5.67-5.60 (m, 1H), δ 2.86-2.77 (m, 1H), δ 2.45-2.19 (m, 3H), δ 2.16-2.04 (m, 1H), δ 2.04-1.95 (m, 1H), δ

1.95-1.82 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 126.5, 122.8, 122.0, 27.7, 24.9, 24.2, 22.4.

3-Phenylpropanenitrile3 (Table 2, entry 11); 1H NMR (400 MHz, CDCl3) δ 7.34 (t, J = 7.2 Hz, 2H), δ

7.28 (d, J = 7.3 Hz, 1H), δ 7.26-7.22 (m, 2H), δ 2.96 (t, J = 7.4 Hz, 2H), δ 2.62 (t, J = 7.4 Hz, 2H); 13C

NMR (101 MHz, CDCl3) δ 137.5, 128.4, 127.8, 126.8, 118.6, 31.1, 18.9.

2-Methyl-3-phenylpropanenitrile3 (Table 2, entry 12); 1H NMR (400 MHz, CDCl3) δ 7.36-7.30 (m,

2H), δ 7.30-7.26 (m, 1H), δ 7.26-7.20 (m, 2H), δ 2.98-2.88 (m, 1H), δ 2.88-2.79 (m, 2H), δ 1.32 (d, J =

6.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 136.9, 129.1, 128.7, 127.3, 122.6, 40.0, 27.5, 17.6.

3-(1,3-Benzodioxol-5-yl)-2-methylpropanenitrile9 (Table 2, entry 13); 1H NMR (400 MHz, CDCl3) δ

6.75 (d, J = 7.8 Hz, 1H), δ 6.72-6.66 (m, 2H), δ 5.92 (s, 2H), δ 2.85-2.71 (m, 3H), δ 1.30 (d, J = 5.9 Hz,

S4

3H); 13C NMR (101 MHz, CDCl3) δ 147.8, 146.8, 130.6, 122.5, 122.2, 109.3, 108.4, 101.1, 39.7, 27.8,

17.5.

4-Methoxybenzonitrile3 (Table 3, entry 1); 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 8.7 Hz, 2H), δ

6.95 (d, J = 8.7 Hz, 2H), δ 3.86 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 162.8, 134.0, 119.2, 114.7, 103.9,

55.5.

4-Methylbenzonitrile6 (Table 3, entry 2); 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.1 Hz, 2H), δ 7.30

(d, J = 7.9 Hz, 2H), δ 2.45 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 143.7, 132.0, 129.8, 119.1, 109.3, 21.8.

4-(Methylthio)benzonitrile10 (Table 3, entry 3); 1H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 8.7 Hz, 2H),

δ 7.26 (d, J = 8.7 Hz, 2H), δ 2.51 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 146.1, 132.1, 125.4, 119.0,

107.6, 14.7.

4-Bromobenzonitrile3 (Table 3, entry 4); 1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 8.6 Hz, 2H), δ 7.45

(d, J = 8.6 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 133.4, 132.6, 128.0, 118.0, 111.2.

4-Chlorobenzonitrile11 (Table 3, entry 5); 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 8.7 Hz, 2H), δ

7.47 (d, J = 8.7 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 139.5, 133.4, 129.7, 117.9, 110.7.

4-(Trifluoromethyl)benzonitrile3 (Table 3, entry 6); 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.2 Hz,

2H), δ 7.77 (d, J = 8.2 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 134.5 (q, J = 33.4 Hz), δ 132.7, δ 126.2

(q, J = 3.6 Hz), δ 123.0 (q, J = 273.0 Hz), δ 117.4, δ 116.0.

S5

4-Nitrobenzonitrile11 (Table 3, entry 7); 1H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.9 Hz, 2H), δ 7.90

(d, J = 8.9Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 150.0, 133.5, 124.3, 118.3, 116.8.

3-Methylbenzonitrile12 (Table 3, entry 8); 1H NMR (400 MHz, CDCl3) δ 7.49-7.31 (m, 4H), δ 2.39 (s,

3H) ; 13C NMR (101 MHz, CDCl3) δ 139.2, 133.6, 132.5, 129.2, 129.0, 119.0, 112.2, 21.1.

2-Methylbenzonitrile12 (Table 3, entry 9); 1H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 7.7 Hz, 1H), δ

7.41 (t, J = 7.6 Hz, 1H), δ 7.24 (d, J = 7.8 Hz, 1H), δ 7.20 (t, J = 7.6 Hz, 1H), δ 2.48 (s, 3H); 13C NMR

(101 MHz, CDCl3) δ 141.9, 132.6, 132.5, 130.2, 126.2, 118.1, 112.7, 20.5.

Piperonylonitrile3 (Table 3, entry 10); 1H NMR (400 MHz, CDCl3) δ 7.14 (d, J = 8.1 Hz, 1H), δ 6.96 (s,

1H), δ 6.79 (d, J = 8.1 Hz, 1H), δ 6.00 (s, 2H); 13C NMR (101 MHz, CDCl3) δ 151.5, 148.0, 128.2, 118.9,

111.4, 109.1, 104.9, 102.2.

2,4,6-Trimethylbenzonitrile12 (Table 3, entry 11); 1H NMR (400 MHz, CDCl3) δ 6.93 (s, 2H), δ 2.48 (s,

6H), δ 2.32 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 142.3, 141.5, 127.7, 117.1, 109.8, 21.1, 20.1.

Cinnamonitrile6 (Table 3, entry 12); 1H NMR (400 MHz, CDCl3) δ 7.52-7.36 (m, 6H), δ 5.88 (d, J =

16.7 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 150.1, 133.0, 130.7, 128.6, 126.9, 117.7, 95.9.

S6

1-Naphtonitrile12 (Table 3, entry 13); 1H NMR (400 MHz, CDCl3) δ 8.22 (d, J = 8.4 Hz, 1H), δ 8.06 (d,

J = 8.4 Hz, 1H), δ 7.90 (t, J = 7.3 Hz, 2H), δ 7.68 (t, J = 7.6 Hz, 1H), δ 7.60 (t, J = 7.6 Hz, 1H), δ 7.51 (t,

J = 7.3 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 133.3, 132.9, 132.6, 132.3, 128.6, 128.6, 127.5, 125.1,

124.9, 117.8, 110.2.

2-Thiophenecarbonitrile6 (Table 3, entry 14); 1H NMR (400 MHz, CDCl3) δ 7.67-7.60 (m, 2H), δ 7.16-

7.12 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 136.9, 132.1, 127.1, 113.7, 109.4.

Isophthalonitrile13 (Table 3, entry 15); 1H NMR (400 MHz, CDCl3) δ 7.97 (s, 1H), δ 7.91 (d, J = 7.9

Hz, 2H), δ 7.67 (t, J = 7.9 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 135.5, 134.9, 129.8, 116.1, 113.7.

5. Procedure for scale up

A 100 mL flame-dried round bottom flask, which was equipped with a magnetic stir bar and charged

with 4-AcNH-TEMPO+BF4- (2.0 equiv, 20 mmol, 6.0 g) and NH4OAc (4.0 equiv, 40 mmol, 3.2 g), was

evacuated and backfilled with nitrogen (this process was repeated 3 times). After 10 mL of AcOH was

added, octanal (10 mmol, 1.6 mL), and AcOH (10 mL) were added in sequence. The reaction mixture was

stirred for 12 h at 70 oC under N2 balloon, and then cooled to room temperature. The reaction was diluted

by adding EtOAc and washed 4 M HCl aqueous solution. Two layers were separated, and the aqueous

layer was extracted with EtOAc. The combined organic layers were washed with Na2CO3 aqueous

solution. The organic layer was dried over MgSO4, filtered, and concentrated to a volume of

approximately 20 mL by evaporator. To eliminate remaining octanal, aqueous 2 M Na2S2O5 aqueous

solution (100 mL) was added to the organic layer and stirred for 2 hours. Two layers were separated, and

the organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by

column chromatography to give octanenitrile (71 %, 0.9 g).

6. Regeneration of 4-AcNH-TEMPO+BF4-

A 100 mL flame-dried round bottom flask, which was equipped with a magnetic stir bar and charged

with 4-AcNH-TEMPO+BF4- (2.0 equiv, 20 mmol, 6.0 g) and NH4OAc (4.0 equiv, 40 mmol, 3.2 g), was

evacuated and backfilled with nitrogen (this process was repeated 3 times). After 10 mL of AcOH was

S7

added, octanal (10 mmol, 1.6 mL), and AcOH (10 mL) were added in sequence. The reaction mixture was

stirred for 12 h at 70 oC under N2 balloon, and then cooled to room temperature. The reaction mixture was

diluted by adding EtOAc and extracted with 4 M HCl aqueous solution. To the obtained aqueous layer,

Na2CO3 aqueous solution was added. The aqueous mixture was extracted with EtOAc. The dark-red

solution was separated, and dried over MgSO4, filtered, and concentrated in vacuo. The orange-white

solid, which is crude 4-AcNH-TEMPO, was obtained. The oxidation of the crude 4-AcNH-TEMPO with

HBF4, NaOCl, and NaBF4 gave 4-AcNH-TEMPO+BF4-. After filtration, the regenerated 4-AcNH-

TEMPO+BF4- was obtained in 50 % (3.0 g). The purity of the regenerated 4-AcNH-TEMPO+BF4

- was

analyzed by melting point (185-186 oC) and 1H NMR spectrum in CF3COOD.1

7. References

(1) Mercadante, M. A.; Kelly, C. B.; Bobbitt, J. M.; Tilley, L. J.; Leadbeater, N. E. Nat. Protoc. 2013, 8,

666–676.

(2) Silberstein, A. L.; Ramgren, S. D.; Garg, N. K. Org. Lett. 2012, 14, 3796–3799.

(3) Kelly, C. B.; Lambert, K. M.; Mercadante, M. A.; Ovian, J. M.; Bailey, W. F.; Leadbeater, N. E.

Angew. Chem. Int. Ed. 2015, 54, 4241–4245.

(4) (a) Vineck, W. C.; Aldrich, C. S.; Borchardt, R. T.; Grunewald, G. L. J. Med. Chem. 1981, 24, 7–12;

(b) Cai, X.; Keshavarz, A.; Omaque, J. D.; Stokes, B. J. Org. Lett. 2017, 19, 2626–2629; (c) DiLabio,

G. A.; Ingold, K. U.; Roydhouse, M. D.; Walton, J. C. Org. Lett. 2004, 6, 4319–4322.

(5) Zhao, H.; Cai, M.-Z.; Hu, R.-H.; Song, C.-S. Synth. Commun. 2001, 31, 3665–3669.

(6) Lambert, K. M.; Bobbitt, J. M.; Eldirany, S. A.; Wiberg, K. B.; Bailey, W. F. Org. Lett. 2014, 16,

6484–6487.

(7) Sasson, R.; Rozen, S.; Org. Lett. 2005, 7, 2177–2179.

(8) Morton, C. J. H.; Gilmour, R.; Smith, D. M.; Lightfoot, P.; Slawin, A. M. Z.; MacLean, E. J.

Tetrahedron 2002, 58, 5547–5565.

(9) Fang, C.; Li, M.; Hu, X.; Mo, W.; Hu, B.; Sun, N.; Jin, L.; Shen, Z. RSC Adv. 2017, 7, 1484–1489.

(10) Zhu, Y.; Li, L.; Shen, Z. Chem. Eur. J. 2015, 21, 13246–13252.

(11) Dornan, L. M.; Cao, Q.; Flanagan, J. C. A.; Crawford, J. J.; Cook, M. J.; Muldoon, M. J. Chem.

Commun. 2013, 49, 6030–6032.

(12) Ishii, G.; Moriyama, K.; Togo, H. Tetrahedron Lett. 2011, 52, 2404–2406.

(13) Kim, J.; Stahl, S. S. ACS Catal. 2013, 3, 1652–1656.

S8

8. 1H and 13C NMR spectra of substrates

Octanenitrile (Table 2, entry 1)

S9

Decanenitrile (Table 2, entry 2)

S10

6-Chlorohexanenitrile (Table 2, entry 3)

S11

2-Ethylhexanenitrile (Table 2, entry 4)

S12

Adamantane-1-carbonitrile (Table 2, entry 5)

S13

2-Methyl-2-phenylpropanenitrile (Table 2, entry 7)

S14

Cyclohexane-1-carbonitrile (Table 2, entry 8)

S15

4-tert-Butylcyclohexanecarbonitrile (Table 2, entry 9)

S16

Cyclohex-3-enecarbonitrile (Table 2, entry 10)

S17

3-Phenylpropanenitrile (Table 2, entry 11)

S18

2-Methyl-3-phenylpropanenitrile (Table 2, entry 12)

S19

3-(1,3-Benzodioxol-5-yl)-2-methylpropanenitrile (Table 2, entry 13)

S20

4-Methoxylbenzonitrile (Table 3, entry 1)

S21

4-Methylbenzonitrile (Table 3, entry 2)

S22

4-(Methylthio)benzonitrile (Table 3, entry 3)

S23

4-Bromobenzonitrile (Table 3, entry 4)

S24

4-Chlorobenzonitrile (Table 3, entry 5)

S25

4-(Trifluoromethyl)benzonitrile (Table 3, entry 6)

S26

4-Nitrobenzonitrile (Table 3, entry 7)

S27

3-Methylbenzonitrile (Table 3, entry 8)

S28

2-Methylbenzonitrile (Table 3, entry 9)

S29

Piperonylonitrile (Table 3, entry 10)

S30

2,4,6-Trimethylbenzonitrile (Table 3, entry 11)

S31

Cinnamonitrile (Table 3, entry 12)

S32

1-Naphthonitrile (Table 3, entry 13)

S33

2-Thiophenecarbonitrile (Table 3, entry 14)

S34

Isophthalonitrile (Table 3, entry 15)

S35