Photoinduced cleavage of N-N bonds of aromatic hydrazines and hydrazides by visible light

Article abstract of DOI:10.1055/s-0030-1260082

A photocatalytic system involving [Ru(bpyrz)(PFH, visible light, and air has been developed for cleavage of the N-N bonds of hydrazines and hydrazides. This catalytic system is generally effective for N,N-disubstituted hydrazine and hydrazide derivatives, including arylhydrazides, N-alkyl-N-arylhydrazines, and N,N-diarylhydrazines. The utility of this cleavage reaction has been demonstrated by synthesizing a variety of secondary aromatic amines. Georg Thieme Verlag Stuttgart ? New York.

Full text of DOI:10.1055/s-0030-1260082

SYNTHESIS
Journal of Synthetic organic Chemistry
SUPPORTING INFORMATION
Supporting Information
for DOI: 10.1055/s-0030-1260082
Georg Thieme Verlag KG Stuttgart · New York 2011
©
Thieme

Supplementary Information for
Photoinduced Cleavage of N-N Bonds by Visible Light
Mingzhao Zhu and Nan Zheng*
Department of Chemistry and Biochemistry,
University of Arkansas,
Fayetteville, AR 72701
(
Experimental part)
Table of contents
1
2
3
4
. Fluorescence quenching experiment
. General procedures I-IV
2
2
3
3
. Experimental set-up for photolytic reactions
. Experimental
1

Fluorescence quenching of [Ru(bpyrz) ](PF ) •2H O (3a) by hydrazide 1a and hydrazine 1b.
3
6 2
2
In a 10 mL of volumetric flask a solution of 3a (9.0 mg, 0.01 mmol, 10 mM) in CH CN was prepared
3
(
solution A). Then 0.1 mL of solution A was added to a 100 mL of volumetric flask and diluted to give
the stock solution of 3a in CH CN (10 μmol/L, solution B). To another 100 mL of volumetric flask
3
were added 0.1 mL of stock solution A and 1a (21.2 mg, 0.1 mmol) and diluted with CH CN to 100
3
mL (solution C, with 10 mM of 1a). Then 1 mL, 2 mL, 4 mL and 8 mL of solution C were added to
four different 10 mL of volumetric flasks and diluted with solution B to give a series of 1a solutions
with the concentration of 1 mM, 2 mM, 4 mM and 8 mM, respectively. The solutions of 1b were
prepared in the same way.
Concentration of
a or 1b
Absorption of 1a
(Excitation at 450 nm;
Absorption of 1b
((Excitation at 450 nm;
1
(mM)
emission detection at 597 nm) emission detection at 596 nm)
0
1
2
4
8
61054
50194
45395
36845
26876
27225
60949
9323
5295
2711
1432
1132
1
0
General procedure I: the synthesis of aryl hydrazines. Substituted aniline (15.5 mmol) was added
slowly to 17.5 mL of aq. HCl (20%) at 0 ˚C to form a suspension. A solution of NaNO (1.13 g, 16
mmol) in 25 mL of H O was added dropwise within 2 h and the temperature was maintained at 0 ˚C
during the addition. The resulted homogenous solution was stirred for another 30 min and SnCl
8.5 g, 37.7 mmol) in 11 mL of conc. HCl was added within 2 h at 0 ˚C to give white precipitates.
Stirring was continued for another 30 min. After filtration, the collected solid product was washed with
ca. 10 mL of cold H O. The obtained arylhydrazine-HCl salt was transferred to a flask and neutralized
with 1 M NaOH solution. The mixture was extracted with CH Cl , dried over MgSO and concentrated
to give crude arylhydrazine that was used directly in the next step.
2
2
.
2
2H O
2
(
2
2
2
4
General procedure II: Boc protection of arylhydrazines. The crude arylhydrazine (10 mmol) was
dissolved in 10 mL of THF and Boc O (10 mmol) was added. The solution was stirred at rt overnight.
2
After the solvent was removed in vacuum, the residue was purified by flash chromatography.
General procedure III: preparation of azo compounds. To a solution of Boc-protected phenyl
hydrazine (5.64 mmol) in CH
2
Cl
2
(10 mL) were added pyridine (11.28 mmol) and NBS (6.21 mmol) at
0
˚C. The solution was stirred for 30 min and concentrated. The mixture was submitted to flash
chromatography to give the azo compound.
General procedure IV: deprotection of N-tert-butoxycarbonyl–N’,N’-disubstituted hydrazines
and hydrazides. To a solution of Boc-hydrazine or hydrazide derivative (0.3 mmol) in CH
2
Cl
2
(5 mL)
was added 0.5 mL of TFA at 0 ˚C. Then the flask was placed in a fridge until no staring material was
found on TLC. Then 10 mL of saturated aqueous Na
2
CO solution was added and the mixture was
3
2

stirred at 0 ˚C for 5 min. The mixture was extracted with CH
2
Cl
2
(3ꢀ20 mL). The combined organic
. The solvents were
solution was washed with H O and brine and dried over anhydrous MgSO
2
4
removed in vacuum to afford the crude N’,N’-disubstituted hydrazine or hydrazide. The hydrazine or
hydrazide was purified by silica gel column. If the hydrazine or hydrazide was not stable in silica gel,
it was then used directly in the next step.
Experimental set-up for photolytic reactions.
Experimental.
N-tert-Butoxycarbonyl-N-phenylhydrazine (1c). This compound was prepared and characterized based
1
on the literature .
N-tert-Butoxycarbonyl-N-(4-trifluromethylphenyl)hydrazine (1d). This compound was prepared and
2
characterized based on the literature .
N’-tert-butoxycarbonyl-N-phenylhydrazine (S1). This compound was prepared and characterized
3
based on the literature .
1
2
3
Wolter, M.; Klapars, A.; Buchwald, S. L. Org. Lett. 2001, 3, 3803.
Lam, M. S.; Lee, H. W.; Chan, A. S. C.; Kwong, F. Y. Tetrahedron Lett. 2008, 49, 6192.
Kisseljova, K.; Tꢁubrik, O.; Sillard, R.; Mäeorg, S.; Mäeorg, U. Org. Lett. 2006, 8, 43.
3

4
N-Propanoylpyrrolidine (S14). This compound was prepared and characterized based on the literature .
NH2
O
H
N
N
BzCl
TFA
NHBoc
N
NHBoc
S2
O
S1
1a
5
N-Benzoyl-N-phenyl-N’-tert-butoxycarbonyl hydrazine (S2). To a mixture of S1 (1.80 g, 8.64 mmol)
and pyridine (2.5 mL) in 10 mL of CH
mmol). The mixture was stirred at rt for 15 h, then was diluted with 250 mL of Et
washed with 1 M aq. HCl (3 ꢀ 10 mL) solution, H O and brine. After dried over anhydrous MgSO
the solution was concentrated. The crude product was purified on silica gel column chromatography
2
Cl
2
at 0 ˚C was added slowly benzoyl chloride (1.00 mL, 8.64
2
O. The solution was
2
4
,
1
(
3:1 hexanes:EtOAc) to give the product as yellow oil (2.53 g, 94%). The H data are consistent with
5
those reported.
5
N-Benzoyl-N-phenylhydrazine (1a). A solution of S2 (2.00 g, 6.41 mmol) in 10 mL of TFA was kept
at 0 ˚C for 15 h. After removing most of TFA, the mixture was diluted with 200 mL of CH Cl . The
solution was washed with saturated aq. Na CO soln., H O and brine and was dried over MgSO . After
concentration, the residue was purified over silica gel column chromatography to give the product as a
2
2
2
3
2
4
6
1
white solid (1.30g, 96%): mp 60-61 ˚C (Lit. mp 63-65 ˚C); H NMR (400 MHz, DMSO-d ) ꢀ 7.26-
6
1
3
7
1
.40 (m, 9H), 7.13-7.17 (m, 1H), 5.50 (s, 2H); C NMR (100 MHz, DMSO-d
6
) ꢀ 168.9, 144.2, 136.3,
29.5, 128.4, 128.3, 127.7, 125.8, 125.5.
HO
NHBoc
H
NH2
N
O
N
TFA
N
NHBoc
O
(
COCl)2
O
S1
S3
1
e
N-tert-Butoxycarbonyl-N’-styrylacetyl-N’-phenylhydrazine (S3). Oxalyl chloride (624 μL, 6.6 mmol)
was added to a solution of trans-styrylacetic acid (531 mg, 3.3 mmol) in CH Cl (5 mL) and DMF (78
μL) at 0 ˚C. When no more gas was evolved, the mixture was heated to reflux for 1.5 h. After
concentration, the solids were dissolved in 10 mL of CH Cl and S1 (750 mg, 3.6 mmol) was added at
˚C followed by pyridine (0.5 mL). The mixture was stirred at rt for 1 h and then diluted with 100 mL
2
2
2
2
0
of EtOAc. After washing with H
2
O and brine, the solution was dried over anhydrous MgSO and
4
concentrated. The residue was purified by silica gel column chromatography (5:1 hexanes:EtOAc) to
-
1
give 460 mg of the product (40%) as white crystals: mp 107-110 ˚C; IR (neat, cm ) 3283, 3066, 3030,
1
2
980, 2936, 1732, 1672, 1597, 1496, 1395, 1371, 1247, 1161, 966, 759, 702; H NMR (400 MHz,
CD OD) ꢀ 7.21-7.47 (m, 10H), 6.19-6.59 (m, 2H), 4.91 (s, 1H), 3.19-3.60 (m, 2H), 1.51/1.37
3
4
5
6
Oare, D. A.; Henderson, M. A.; Sanner, M. A.; Heathcock, C. H. J. Org. Chem. 1990, 55, 132.
Yamasaki, R.; Tanatani, A.; Azumaya, I.; Masu, H.; Yamaguchi, K.; Kagechika, H. Crystal Growth & Design 2006, 9, 2007.
Baumgarten, H. E.; Chen, P. Y.-N.; Taylor, H. W; Hwang, D.-R. J. Org. Chem. 1976, 41, 3805.
4

1
3
(
rotamers, 2 ꢀ s, 9H); C NMR (100 MHz, CD
3
OD) ꢀ 176.3, 158.1/157.6, 144.4/143.8, 139.2, 135.4,
1
31.4, 130.6/130.4, 129.5/129.3, 128.8, 128.1, 126.6, 124.1, 83.6/83.0, 39.9/39.5, 29.4; HRMS (ESI)
+
m/z calcd. for C21
H
24
N
2
3
O Na [M+Na] 375.1679, found 375.1678.
N-Styrylacetyl-N-phenylhydrazine (1e). Following the general procedure IV except that the reaction
was carried in CH Cl (3 mL) and TFA (1 mL) at rt for 15 h, 460 mg of S3 (1.31 mmol) gave the
product (210 mg, 64%) after purification on silica gel column chromatography (5:1 hexanes:EtOAc):
2
2
-
1
1
IR (neat, cm ) 3336, 3222, 3061, 3030, 1633, 1392, 1127, 969, 697; H NMR (400 MHz, CDCl )
3
1
3
ꢀ
7.19-7.46 (m, 10H), 6.27 (s, 2H), 4.86 (s, 2H), 3.17 (s, 2H); C NMR (100 MHz, CDCl
3
) ꢀ 169.9,
1
42.3, 136.8, 133.0, 129.4, 128.4, 128.1, 127.4, 126.9, 126.2, 122.7, 37.9. Anal. calcd. for C16
H
16
N
2
O:
C, 76.16; H, 6.39; N, 11.10. Found: C, 75.86; H, 6.19; N, 10.89.
N
N
O
H
N
O
N
O
N
N
N
Cl
NHBoc
TFA
N
+
NHBoc
N
NH2
S1
S4
S5
1f
7
Pyrazinecarbonyl Chloride (S4) . A solution of pyrazinecarboxylic acid (2.48 g, 20 mmol), thionyl
chloride (2.18 mL, 30 mmol) in toluene (15 mL) was refluxed for 1 h. The color of the reaction
mixture turned purple. After removing the precipitates by filtration, the solution was concentrated in
1
vacuo to give red solids (2.16 g, ca. 76%) that were used for the next step without purification: H
NMR (400 MHz, DMSO-d
C NMR (100 MHz, DMSO-d ) ꢀ 165.0, 147.8, 145.6, 144.7, 143.8.
6
) ꢀ 9.18 (d, J = 1.4 Hz, 1H), 8.86 (d, J = 2.4 Hz, 1H), 8.79-8.80 (m, 1H);
1
3
6
N-tert-Butoxycarbonyl-N’-phenyl-N’-pyrazinecarbonylhydrazide (S5). To a stirred solution of S1 (521
mg, 2.5 mmol) and S4 (356 mg, 2.5 mmol) in CH Cl (4 mL) was added Et N (348 μL, 2.5 mmol).
The mixture was allowed to warm up to rt within 2 h and then stirred for 15 h. The mixture was loaded
to silica gel column chromatography (30:1 CH Cl :THF) directly to get the pure product (750 mg,
5%) as white crystals: mp 160-161 ˚C; IR (neat, cm ) 3294, 3067, 2983, 2938, 1736, 1686, 1496,
2
2
3
2
2
-
1
9
1
5
1
1
372, 1253, 1162, 1021, 762, 702; H NMR (400 MHz, CD
3
OD) ꢀ 8.50-8.90 (m, 3H), 7.23-7.56 (m,
) ꢀ 167.4, 154.4, 149.5, 145.6, 143.8/143.5,
43.1, 140.9, 128.8, 126.6, 123.1, 80.5, 27.7. Anal. calcd. for C16 : C, 61.13; H, 5.77; N, 17.82.
1
3
H), 1.33-1.50 (m, 9H); C NMR (100 MHz, DMSO-d
6
H
18
N
4
O
3
Found: C, 61.42; H, 5.90; N, 17.89.
N-Phenyl-N-pyrazinecarbonylhydrazide (1f). Following the general procedure IV except that the
reaction was carried at rt for 6 h, S5 (150 mg, 0.48 mmol) gave 63 mg of 1f (61%) as white crystals
after purification on silica gel column chromatography (5:1 CH
cm ) 3320, 3206, 3066, 2926, 1654, 1597, 1496, 1379, 1021, 769, 699; H NMR (400 MHz, CDCl
2
Cl
2
:THF): mp 126-127 ˚C; IR (neat,
-
1
1
3
)
1
3
ꢀ
8.73 (brs, 1H), 8.49 (brs, 1H), 8.38 (brs, 1H), 7.17-7.29 (m, 5H), 5.04 (brs, 2H); C NMR (100
7
Cynamon, M. H.; Gimi, R.; Gyenes, F.; Sharpe, C. A.; Bergmann, K. E.; Han, H. J.; Gregor, L. B.; Rapolu, R.; Luciano,
G.; Welch, J. T. J. Med. Chem. 1995, 38, 3902.
5

MHz, CDCl ) ꢀ 165.2, 149.0, 145.0, 144.7, 143.2, 142.1, 128.9, 127.2, 126.0. HRMS (ESI) m/z calcd.
3
+
for C11
H
11
4
N O [M+H] 215.0927, found 215.0922.
NHBoc
NH2
N
NHBoc
N
NH nBuLi
TFA
BnBr
S6
1g
S1
8
N-tert-Butoxycarbonyl-N’-benzyl-N’-phenylhydrazine (S6) . A solution of S1 (1.13 g, 5.42 mmol) in
5 mL of THF was cooled to -78 ˚C and n-BuLi (1.6 M in THF, 7.45 mL, 11.9 mmol) was added
dropwise. After 30 min, benzyl bromide (714 μL, 5.97 mmol) in 2 mL of THF was added. The solution
was stirred at 0 ˚C for 1 h and was quenched with saturated aq. NH Cl solution. The mixture was
extracted with Et O (3 ꢀ 20 mL). The combined organic layers were washed with H O, brine, and
dried over anhydrous MgSO . After removing the solvents in vacuo, the residue was purified by on
silica gel column chromatography (10:1 hexanes:EtOAc) to give the product as white crystals (1.41 g,
2
4
2
2
4
1
5
1
13
8
7%): mp 91-93 ˚C (Lit. mp 92-94 ˚C). The H and C NMR data are consistent with those
1
7
reported.
9
N-Benzyl-N-phenylhydrazine (1g) . Starting from 122 mg of compound S6 (0.41 mmol), the crude
1
product (81 mg, ca. 100%) was obtained based on the general procedure IV: H NMR (400 MHz,
1
3
CDCl ) ꢀ 7.27-7.39 (m, 7H), 7.11-7.15 (m, 2H), 6.82-6.87 (m, 1H), 4.62 (s, 2H), 3.58 (s, 2H); C
3
NMR (100 MHz, CDCl
3
) ꢀ 148.1, 139.4, 129.2, 128.6, 127.5, 127.2, 117.5, 112.8, 48.3.
Cl
Cl
Cl
Cl
H
N
H
Bn
NH2
NaNO2
N
Boc O
N
2
NHBoc nBuLi
BnBr
NH2
NHBoc
then SnCl2
S7
S8
Cl
NH2
N
TFA
1h
N-tert-Butoxycarbonyl-N’-(4-chlorophenyl)hydrazine (S7). Following the general procedure I and II,
-chloroaniline (2.1 mL, 20 mmol) gave 2.2 g of S7 (45%, two steps) as white crystals after
2
-
purification on silica gel column chromatography (20:1 hexanes:EtOAc); mp 107-109 ˚C; IR (neat, cm
1
1
)
3334, 3010, 2990, 2972, 2934, 1707, 1598, 1489, 1282, 1249, 1163, 1036, 750; H NMR (400
MHz, CDCl ) ꢀ 7.26 (dd, J = 7.8 Hz, J = 1.4 Hz, 1H), 7.16-7.20 (m, 1H), 6.95 (dd, J = 8.2 Hz, J = 1.1
Hz, 1H), 6.81 (td, J = 7.7 Hz, J = 1.4 Hz, 1H), 6.36 (brs, 1H), 6.22 (brs, 1H), 1.47 (s, 9H); C NMR
100 MHz, CDCl ) ꢀ 155.8, 144.1, 129.2, 127.5, 120.7, 118.7, 113.1, 81.4, 28.1. Anal. calcd. for
: C, 54.44; H, 6.23; N, 11.54. Found: C, 54.56; H, 6.23; N, 11.60.
3
1
3
(
C
3
11
H
15ClN
2
O
2
8
9
Bredihhin, A.; Groth, U. M.; Mäeorg, U. Org. Lett. 2007, 9, 1097.
Nara, S.; Sakamoto, T.; Miyazawa, E.; Kikugawa, Y. Synth. Commun. 2003, 33, 87.
6

N-tert-Butoxycarbonyl-N’-benzyl-N’-(2-chlorophenyl)hydrazine (S8). n-Butyllithium (1.6 M in THF,
.8 mL, 2.9 mmol) was added to S7 (324 mg, 1.33 mmol) in THF (20 mL) at – 78 ˚C. After 15 min, a
solution of benzyl bromide (162 μL, 1.33 mmol) in 2 mL of THF was added. Temperature increased to
˚C and the reaction was stirred for 1 h at that temperature. Then it was quenched with aq. saturated
NH Cl solution. After extracting with Et O (3 ꢀ 20 mL), the combined organic layers were washed
with H O, brine, and dried over anhydrous MgSO . The solvents were removed in vacuo and the
residue was purified on silica gel column chromatography to give S8 (386 mg, 87%) as white crystals:
1
0
4
2
2
4
-
1
mp 116-118 ˚C; IR (neat, cm ) 3411, 3323, 3247, 3068, 3032, 2980, 2933, 1703, 1480, 1369, 1252,
1
1
9
1
161, 756, 702; H NMR (400 MHz, DMSO-d
H), 4.38/4.27 (rotamers, 2 ꢀ brs, 2H), 1.21-1.42 (m, 9H); C NMR (100 MHz, CDCl
46.5, 136.8, 130.4, 128.9, 128.4, 128.1, 127.5, 126.9, 124.8, 122.6, 80.4, 57.0, 28.2; HRMS (ESI) m/z
6
) ꢀ 8.95/8.57 (rotamers, 2 ꢀ brs, 1H), 6.69-7.52 (m,
1
3
3
) ꢀ 154.5,
+
calcd. for C18
H
21ClN
2
2
O Na [M+Na] 355.1184, found 355.1183.
N-Benzyl-N-(2-chlorophenyl)hydrazine (1h). Compound S8 (130 mg, 0.39 mmol) was submitted to the
deprotection reaction following the general procedure IV to give crude hydrazine (90 mg, ca. 99%) as
1
yellow oil: H NMR (400 MHz, CDCl
3
) ꢀ 7.43-7.46 (m, 2H), 7.32-7.40 (m, 5H), 7.25 (ddd. J = 8.1 Hz,
1
3
J = 7.3 Hz, J = 1.5 Hz, 1H), 7.00-7.04 (m, 1H), 4.30 (s, 2H), 3.54 (brs, 2H); C NMR (100 MHz,
CDCl
3
) ꢀ 149.9, 136.9, 130.4, 128.8, 128.5, 127.6, 127.3, 127.1, 124.2, 121.2, 64.2.
NHBoc
NH2
N
NHBoc
N
N
Pd(OAc)2
Cl
Cl
B(OH)2
TFA
I
5v
S9
1
i
Cl
N-tert-Butoxycarbonyl-N’-butyl-N’-(3’-chlorobiphenyl-4-yl)hydrazine (S9). A mixture of 5v (156 mg,
.4 mmol), 3-chlorophenylboronic acid (64 mg, 0.41 mmol), Pd(OAc) (1.8 mg, 8 μmol), K CO (132
mg, 0.96 mmol), H O (1.1 mL) and acetone (2.5 mL) in a sealed tube was degassed using freeze-
pump-thaw (4 cycles). The tube was sealed and heated at 65 ˚C for 2 h. After diluted with Et O (100
mL), the solution was washed with H O, brine, and dried over anhydrous MgSO . After concentration,
the residue was purified on silica gel column chromatography (10:1 hexanes:Et O) to give the product
117 mg, 78%) as colorless oil: IR (neat, cm ) 3302, 2965, 2936, 2874, 1709, 1613, 1524, 1478, 1371,
0
2
2
3
2
2
2
4
2
-
1
(
1
1
7
3
(
5
3
164, 782; H NMR (400 MHz, CDCl
3
) ꢀ 7.52 (brs, 1H), 7.46 (d, J = 8.7 Hz, 2H), 7.40-7.44 (m, 1H),
.31 (t, J = 7.8 Hz, 1H), 7.22-7.25 (m, 1H), 6.86-6.90 (m, 2H), 6.42/6.14 (rotamers, 2 ꢀ brs, 1H), 3.43-
1
3
.54 (m, 2H), 1.66 (quintet, J = 7.4 Hz, 2H), 1.33-1.15 (m, 11H), 0.98 (t, J = 7.4 Hz, 3H); C NMR
) ꢀ 154.8, 149.0, 142.8, 134.5, 130.2, 129.8, 127.8, 126.4, 126.2, 124.5, 112.8, 81.0,
100 MHz, CDCl
3
-
2.2, 28.7, 28.3, 20.2, 13.9; HRMS (ESI) m/z calcd. for C21
H
28ClN
2
O [M+H] 375.1834, found
2
75.1834.
N-Butyl-N-(3’-chlorobiphenyl-4-yl)hydrazine (1i). Following the general procedure IV, 120 mg of S9
-
1
(
2
0.32 mmol) gave 87 mg of the crude product in ca. 100% yield: IR (neat, cm ) 3346, 3071, 3037,
1
959, 2931, 2871, 1615, 1594, 1519, 1475, 1200, 1101, 782; H NMR (400 MHz, CDCl ) ꢀ 7.56 (t, J =
3
1
.9 Hz, 1H), 7.46-7.50 (m, 2H), 7.43-7.46 (m, 1H), 7.32 (t, J = 7.8 Hz, 1H), 7.23-7.25 (m, 1H), 7.02-
7

7
1
1
.05 (m, 2H), 3.64 (m, 2H), 3.45 (t, J = 7.5 Hz, 2H), 1.63-1.71 (m, 2H), 1.42 (sextet, J = 7.5 Hz, 2H),
1
3
.00 (t, J = 7.4 Hz, 3H); C NMR (100 MHz, CDCl
3
) ꢀ 151.3, 142.9, 134.5, 129.8, 128.7, 127.6,
26.3, 126.0, 124.3, 113.1, 55.1, 27.9, 20.2, 14.0.
N
N
N
nBuLi
nBuLi
NH2
N
H
N
MeI
MeI
1b
1k
1j
1
0
N’-Methyl-N-methyl-N-phenylhydrazine (1k) . To a stirred solution of N-methyl-N-phenylhydrazine
1.21 mL, 10 mmol) at -78 ˚C was added n-butyllithium (1.6 M in THF, 5.9 mL, 9.5 mmol). After 30
min, the temperature was increased to 0 ˚C and CH I (685 μL) was added. The reaction was quenched
with saturated aq. NH Cl soln. and extracted with Et O (3 ꢀ 20 mL). The combined organic layers
were washed with H O, brine, and dried over anhydrous MgSO . After concentration in vacuo, the
residue was purified on silica gel column chromatography (6:1 hexanes:EtOAc) to give the product
(
3
4
2
2
4
1
13
21
(
111 mg, 86%) as colorless oil. The H and C NMR data are consistent with those reported.
1
1
Trimethylphenylhydrazine (1j) . To a solution of 1k (235 mg, 1.73 mmol) in 10 mL of THF was
added n-BuLi (1.6 M in THF, 1.08 mL, 1.73 mmol) at -20 ˚C. After 15 min, the reaction mixture was
warmed to 0 ˚C and MeI (108 μL, 1.73 mmol) was added. The reaction was quenched with saturated
aq. NH
organic layers were washed with H
vacuo, the residue was purified on silica gel column chromatography (5:1 ꢀ 2:1 haxanes:CH
4
Cl solution after 30 min. The mixture was extracted with Et
2
O (3 ꢀ 20 mL). The combined
. After concentration in
Cl ) to
) ꢀ 7.21-7.26 (m, 2H), 7.01-7.03 (m,
2
O, brine, and dried over anhydrous MgSO
4
2
2
1
give 1j as yellow oil (168 mg, 65%): H NMR (400 MHz, CDCl
3
1
3
2
H), 6.74 (tt, J = 7.3 Hz, J = 1.1 Hz, 1H), 2.78 (s, 3H), 2.47 (s, 6H); C NMR (100 MHz, CDCl ) ꢀ
3
1
50.2, 128.8, 117.6, 112.8, 41.0, 26.6.
N
N
NH2
BnBr
N
H
1b
1l
1
2
N-Methyl-N-phenyl-N’-benzylhydrazine (1l) . To a solution of N-methyl-N-phenylhydrazine (353 μL,
mmol) in THF at -78 ˚C was added n-butyllithium (1.6 M in THF, 2.1 mL, 3.3 mmol) dropwise.
After stirring for 20 min, benzyl bromide (356 μL, 3 mmol) was added and the solution was warmed to
˚C. After 30 min, the reaction was quenched with saturated aq. NH Cl solution and extracted with
Et O (3ꢀ30 mL). The combined organic layers were washed with H O, brine, dried over Na SO , and
concentrated in vacuo. The residue was purified by silica gel chromatography (50:1 ꢀ 20:1
3
0
4
2
2
2
4
1
hexanes:EtOAc) to give the product as a pale yellow oil (433 mg, 68%): H NMR (400 MHz, CDCl
3
)
ꢀ
7.45-7.48 (m, 2H), 7.36-7.41 (m, 2H), 7.27-7.34 (m, 3H), 7.05-7.08 (m, 2H), 6.81-6.85 (m, 1H), 4.07
1
3
(s, 2H), 3.51 (brs, 1H), 3.14 (s, 3H); C NMR (100 MHz, CDCl
3
) ꢀ 151.0, 138.2, 129.0, 128.9, 128.4,
1
27.4, 118.2, 113.3, 52.0, 39.5.
1
1
1
0 Hisler, K.; Commeureuc, A. G. J.; Zhou, S.; Murphy, J. A. Tetrahedron Lett. 2009, 50, 3290.
1 Guimanini, A. G.; Chiavari, G.; Musiani, M. M.; Rossi, P. Synthesis 1980, 743.
2 Perkins, M. J.; Smith, B. V.; Turner, E. S. J. Chem. Soc., Chem. Comm. 1980, 20, 977.
8

H
N
N
nBuLi
N
N
H
H
MeI
1m
1
3
N’-phenyl-N-methylphenylhydrazine (1m) . n-BuLi (1.6 M in THF, 2.1 mL, 3.3 mmol) was added
dropwise to a solution of N,N’-diphenylhydrazine (553 mg, 3.0 mmol) in THF (10 mL) at -78 ˚C. After
3
0 min, MeI (280 μL, 4.5 mmol) was added at the same temperature. The reaction was stirred at rt
overnight and quenched with saturated aq. NH Cl soln. After extracting with Et O (3 ꢀ 20 mL), the
combined organic layers were washed with H O, brine, and dried over anhydrous MgSO . The solution
was concentrated and the residue was purified with silica gel column chromatography (50:1 ꢀ 10:1
4
2
2
4
1
4
hexanes:CH
H NMR (400 MHz, CDCl
2
Cl
2
) to give the product as white crystals (355 mg, 60%): mp 72-74 ˚C (Lit. mp 75 ˚C);
) ꢀ 7.21-7.28 (m ,4H), 6.95-6.98 (m, 2H), 6.81-6.87 (m, 4H), 5.48 (brs,
1
3
1
3
1
1
H), 3.17 (s, 3H); C NMR (100 MHz, CDCl
12.82, 112.41, 39.70.
3
) ꢀ 150.78, 147.42, 129.36, 129.10, 119.77, 118.82,
Cl
Cl
H
N
Boc
N
NBS
Py
N
NHBoc
4n
S7
N-tert-Butoxycarbonyl-N’-(2-chlorophenyl)diazene (4n). Following the general procedure III, 3n (1.06
g, 4.37 mmol) afforded 1.04 g of the product (99%) as red oil after purification on silica gel column
-
1
chromatography (50:1 hexanes:EtOAc): IR (neat, cm ) 3068, 2985, 2939, 2876, 1758, 1509, 1465,
1
1
371, 1275, 1255, 1153, 1121, 1065, 842, 769; H NMR (400 MHz, CDCl
3
) ꢀ 7.56-7.60 (m, 2H), 7.48
(
(
ddd, J = 8.1 Hz, J = 7.3 Hz, J = 1.7 Hz, 1H), 7.32 (ddd, J = 8.1 Hz, J = 7.4 Hz, J = 1.5 Hz, 1H), 1.67
1
3
s, 9H); C NMR (100 MHz, CDCl
3
) ꢀ 160.7, 147.8, 136.8, 133.9, 131.0, 127.2, 117.2, 85.3, 27.8.
Anal. calcd. for C11
H13ClN
2
O
2
: C, 54.89; H, 5.44; N, 11.64. Found: C, 55.18; H, 5.42; N, 11.69.
NBS
Py
N
Boc
NaNO2
Boc O
N
2
F3C
NH2
F3C
NHNH2
F3C
NHNHBoc
then SnCl2
F3C
S10
4o
N-tert-Butoxycarbonyl-N’-(4-trifluoromethylphenyl)hydrazine (S10). Following the general procedure
I, 2.5 g of 4-trifluoromethyl aniline (15.5 mmol) afforded crude 4-trifluoromethyl-phenylhydrazine
(
2.1 g, ca. 77%) as yellow solid. Without further purification, the solid was submitted to the Boc-
protection based on the general procedure II. The desired product was obtained from silica gel
-
1
chromatography (5:1 hexanes:EtOAc) as white crystals (2.9 g, 29%): mp 124-125 ˚C; IR (neat, cm )
1
3
305, 3081, 3009, 2988, 2941, 1693, 1623, 1332, 1257, 1161, 1112, 1017, 834; H NMR (400 MHz,
1
1
3 Yeung, D. W. K.; Warkentin, J. Can. J. Chem. 1980, 58, 2386.
4 Banthorpe, D. V.; O’Sullivan, M. J. Chem. Soc., Perkin Trans. 2 1973, 571.
9

CDCl
3
) ꢀ 7.48 (d, J = 8.5 Hz, 2H), 6.86 (d, J = 8.5 Hz, 2H), 6.40 (brs, 1H), 5.94 (brs, 1H), 1.47 (s, 9H);
C NMR (100 MHz, CDCl ) ꢀ 155.9, 151.1, 126.6 (q, J = 3.6 Hz), 124.5 (q, J = 271.2 Hz), 122.5 (q, J
32.7 Hz), 112.2, 81.8, 28.2. Anal. calcd. for C12 : C, 52.17; H, 5.47; N, 10.14. Found: C,
2.06; H, 5.39; N, 10.08.
1
3
3
=
5
H
15
F
3
N
2
O
2
N-tert-Butoxycarbonyl-N’-(4-trifluoromethylphenyl)diazene (4o). Following the general procedure III,
o (2.3 g, 8.3 mmol) gave the desired product 4o (2.1 g, 92%) as orange oil after silica gel
3
-
1
chromatography (50:1 hexanes:EtOAc): IR (neat, cm ) 2988, 2940, 1764, 1375, 1329, 1278, 1261,
1
1
2
3
175, 1152, 1066, 861; H NMR (400 MHz, CDCl
3
) ꢀ 7.98 (d, J = 8.5 Hz, 2H), 7.78 (d, J = 8.5 Hz,
) ꢀ 160.8, 153.2, 134.3 (q, J = 32.5 Hz), 126.4 (q, J =
.7 Hz), 123.6, 123.5 (q, J = 271.0 Hz), 85.6, 27.8. Anal. calcd. for C12 : C, 52.56; H, 4.78;
1
3
H), 1.66 (s, 9H); C NMR (100 MHz, CDCl
3
H
13
F
3
N
2
O
2
N, 10.21. Found: C, 52.44; H, 4.75; N, 10.01.
H
N
NBS,
NHBoc Py
N
Boc
N
S1
4p
3
N-tert-Butoxycarbonyl-N’-phenyldiazene (4p). Following the general procedure III, S1 (1.91 g, 9.17
mmol) was converted to 4p. After purification with silica gel column chromatography (100:1
1
13
hexanes:EtOAc), the product was obtained as red oil (1.81 g, 96%). The H and C NMR data are
3
consistent with those reported.
NH2
NHNH2
Br
NHNNBoc
Br
Br
Br
NaNO2
Boc
2
O
NBS
Py
N Boc
N
then SnCl2
4
s
S11
S12
1
5
N-(5-Bromo-2-methylphenyl)hydrazine (S11). This compound was prepared based on the general
procedure I. 5-Bromo-2-methylaniline (1.92 mL, 15.5 mmol) gave 2.3 g of the crude product as yellow
1
oil (74%): H NMR (400 MHz, DMSO-d
6
) ꢀ 7.19 (brs, 1H), 7.06 (d, J = 8.3 Hz, 1H), 7.02 (d, J = 8.3
1
3
Hz, 1H), 6.11 (brs, 1H), 4.56 (brs, 2H), 2.17 (s, 3H); C NMR (100 MHz, CDCl
29.3, 128.9, 112.2, 107.8, 20.0.
3
) ꢀ 145.3, 132.6,
1
N-tert-Butoxycarbonyl-N’-(2-bromo-4-methylphenyl)hydrazine (S12). Following the general
procedure II, crude S11 (2.1g, ca. 10.4 mmol) gave 2.9 g of the desired product as yellow crystals after
-
purification with silica gel column chromatography (10:1 hexanes:EtOAc): mp 72-74 ˚C; IR (neat, cm
)
1
1
3337, 3037, 3006, 2981, 2931, 2873, 1718, 1506, 1367, 1281, 1246, 1165, 1042, 815; H NMR (400
MHz, DMSO-d ) ꢀ 8.91/8.53 (rotamers, 2 ꢀ brs, 1H), 7.52 (s, 1H), 7.02 (d, J = 8.2 Hz, 1H), 6.91 (s,
6
1
3
1
H), 6.63 (d, J = 7.9 Hz, 1H), 2.18 (s, 3H), 1.41/1.26 (rotamers, 2 ꢀ s, 9H); C NMR (100 MHz,
DMSO-d
6
) ꢀ 155.8, 143.8, 132.4, 129.0, 128.8, 112.8, 106.5, 79.1, 28.1, 19.6. Anal. calcd. for
C
12
H
17BrN
2
O
2
: C, 47.85; H, 5.69; N, 9.30. Found: C, 48.01; H, 5.76; N, 9.23.
1
5 Stroh, H.-H.; Wetphal, G. Chem. Ber. 1964, 97, 83.
1
0

N-tert-Butoxycarbonyl-N’-(2-bromo-4-methylphenyl)diazene (4s). Following the general procedure
III, S12 (1.7 g, 5.6 mmol) afforded 1.6 g of the product (95%) as yellow crystals after purification on
-
1
silica gel column chromatography (50:1 hexanes:EtOAc): mp 89-91 ˚C; IR (neat, cm ): 3478, 3009,
1
2
8
1
5
980, 2941, 1750, 1371, 1257, 1156, 819; H NMR (400 MHz, CDCl
3
) ꢀ 7.59 (brs, 1H), 7.50 (d, J =
1
3
.2 Hz, 1H), 7.14-7.17 (m, 1H), 2.41 (s, 3H), 1.66 (s, 9H); C NMR (100 MHz, CDCl ) ꢀ 160.6,
46.9, 145.6, 134.5, 128.8, 127.6, 117.1, 85.1, 27.9, 21.3. Anal. calcd. for C12
.05; N, 9.36. Found: C, 48.27; H, 4.99; N, 9.38.
3
H15BrN
2
O
2
: C, 48.18; H,
O
O
H
H
NH2
N
NaNO2
SnCl2
N
N
NH2 Boc O
2
O
N
N
O
H
I
NBS,
Py
I
I
I
S13
4v
N-tert-Butoxycarbonyl-N’-(4-iodophenyl)hydrazine (S13). Based on the general procedure I, 4-
iodoaniline (8.76 g, 40 mmol) was converted to 4-iodophenylhydrazine. The crude product was
subjected to the general procedure II to provide compound S13 as white crystals (7.0 g, 52%, two
steps) after purification on a silica gel chromatography (20:1 hexanes:EtOAc): mp 136-138 ˚C; IR
-
1
1
(
(
(
neat, cm ) 3312, 3006, 2981, 2933, 1716, 1595, 1488, 1370, 1278, 1248, 1162, 1000, 821; H NMR
400 MHz, CDCl ) ꢀ 7.48-7.52 (m, 2H), 6.61 (d, J = 8.7 Hz, 2H), 6.34 (brs, 1H), 5.69 (brs, 1H), 1.46
s, 9H); C NMR (100 MHz, CDCl ) ꢀ 156.0, 148.2, 137.8, 115.1, 82.4, 81.5, 28.2. Anal. calcd. for
: C, 39.54; H, 4.52; N, 8.38. Found: C, 39.67; H, 4.59; N, 8.37.
3
1
3
3
C
11
H
15IN
2
O
2
N-tert-Butoxycarbonyl-N’-(4-iodophenyl)diazene (4v). A solution of NBS (294 mg, 1.65 mmol) and
pyridine (242 μL, 3.00 mmol) in 5 mL of CH Cl was cooled to -40 ˚C. Then S13 (500 mg, 1.50
mmol) in 2 mL of CH Cl was added dropwise. The reaction was completed after 10 min at the same
2
2
2
2
temperature. The solution was concentrated in vacuo and the residue was purified on silica gel column
chromatography (100:1 hexanes:EtOAc) to give the pure product (498 mg, 100%): mp 64-66 ˚C; IR
-
1
(
1
9
C
neat, cm ) 3488, 3092, 3006, 2986, 2938, 1756, 1582, 1501, 1400, 1372, 1276, 1259, 1162, 1145,
1
009, 843, 835, 782; H NMR (400 MHz, CDCl
H); C NMR (100 MHz, CDCl
3
) ꢀ 7.86-7.89 (m, 2H), 7.60-7.63 (m, 2H), 1.65 (s,
) ꢀ 160.9, 150.8, 138.6, 124.9, 101.0, 85.3, 27.8. Anal. calcd. for
: C, 39.78; H, 3.95; N, 8.43. Found: C, 40.08; H, 3.94; N, 8.47.
1
3
3
11
H
13IN
2
O
2
1
1

Supplementary Information for
Photoinduced Cleavage of N-N Bonds by Visible Light
Mingzhao Zhu and Nan Zheng*
Department of Chemistry and Biochemistry, University of Arkansas
1
13
(
Copies of H and C NMR)
Unless otherwise noted, all the spectra were recorded in CDCl3.

2.000
1.113
8.584
0.717
10.352

10.000
1
.982
.364
1
1
.448
.702
0
10.529

1
76.341
73.406
1
158.098
157.560
144.441
143.757
139.239
135.446
131.442
130.849
130.613
130.368
129.509
129.313
128.794
128.114
126.578
124.135
8
3.574
3.019
8
3
9.894
9.521
3
29.402

0.744
1
.011
.000
1

165.022
147.801
145.609
144.676
143.791
40.136
39.927
39.719
39.510
39.301
39.093
38.885

2
.557
.000
5
11.248

167.379
154.354
149.534
145.602
143.777
143.464
143.188
140.900
128.837
126.612
123.086
80.502
27.686

7.037
2
.000
.099
1
0
0
.708
.210
2.246
10.837

1
54.681
49.201
1
137.122
129.132
128.573
127.911
127.359
119.411
112.861
80.839
77.319
77.001
76.683
56.480
28.216

1.349
1.066
0.947
1.000
2.062
11.264

1
55.813
44.143
1
1
29.226
27.535
1
1
20.750
18.743
1
113.139
81.361
77.318
77.000
76.682
28.105

0
.819
.265
0
9
.094
.164
0
2.001
9.245

154.507
146.491
136.796
130.374
128.939
128.354
128.117
127.495
126.873
124.808
122.607
80.411
77.318
77.001
76.683
56.973
28.165

1.000
2.167
1.153
1.082
0.861
2.080
0
.688
.253
0
2.354
2.381
12.602
3.301

1
54.783
48.992
1
142.817
134.468
130.163
129.819
127.814
126.412
126.169
124.468
112.776
80.960
77.317
77.000
76.682
52.165
2
8.697
8.277
2
2
0.234
3.943
1

1.918
2.000
0.944
1.071
11.195

1
55.946
51.145
1
126.572
126.536
125.880
123.190
122.639
122.314
112.232
81.761
77.317
77.000
76.682
28.180