Metal-free synthesis of secondary amines by the reaction of tosyl triazene and aryl boronic acid

Article abstract of DOI:10.1080/00397911.2017.1410175

A metal free noncatalytic amination process has been developed for the synthesis of N-substituted aniline using a new amine source. The amine source p-toluene sulfonyl triazene (PhN?NNHTs) has been prepared by treating aryldiazonium salt with p-tosylamide. Various unsymmetrical amines could be synthesized by treating this reagent and boronic acid in toluene at 110 °C in the presence of DBU and 4 ? molecular sieve. A large variety of N-substituted aniline could be synthesized with moderate yield.

Full text of DOI:10.1080/00397911.2017.1410175

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Metal-free synthesis of secondary amines by the
reaction of tosyl triazene and aryl boronic acid
Manas Jyoti Sarma & Prodeep Phukan
To cite this article: Manas Jyoti Sarma & Prodeep Phukan (2018): Metal-free synthesis
of secondary amines by the reaction of tosyl triazene and aryl boronic acid, Synthetic
Communications, DOI: 10.1080/00397911.2017.1410175
To link to this article: https://doi.org/10.1080/00397911.2017.1410175
View supplementary material
Published online: 13 Feb 2018.
Submit your article to this journal
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsyc20

SYNTHETIC COMMUNICATIONS®
https://doi.org/10.1080/00397911.2017.1410175
Metal-free synthesis of secondary amines by the reaction
of tosyl triazene and aryl boronic acid
Manas Jyoti Sarma and Prodeep Phukan
Department of Chemistry, Gauhati University, Guwahati, Assam, India
ABSTRACT
ARTICLE HISTORY
Received 4 October 2017
A metal free noncatalytic amination process has been developed for
the synthesis of N-substituted aniline using a new amine source. The
amine source p-toluene sulfonyl triazene (PhN NNHTs) has been
prepared by treating aryldiazonium salt with p-tosylamide. Various
unsymmetrical amines could be synthesized by treating this reagent
and boronic acid in toluene at 110 °C in the presence of DBU and 4 Å
molecular sieve. A large variety of N-substituted aniline could be
synthesized with moderate yield.
KEYWORDS
=
Amination; boronic acid;
C–N bond formation;
triazene
GRAPHICAL ABSTRACT
Introduction
Development of greener synthetic methods without using metal catalyst is of immense
interest to organic chemists, particularly for the formation of C‒C and C‒N bond.
Nitrogen containing structural motifs are commonly available in biologically active
molecules, including those obtained from natural resources as well as in industrially
important compounds. Hence, development of a new methodology for C‒N bond form-
ing processes is one of the most challenging tasks for organic chemist. Among different
methods available in the literature, metal catalyzed amination, cross coupling and
nitrene transfer processes are the widely utilized pathways for the construction of C‒N
bond. In the recent past, a number of different transition metal catalysts have been
developed for C‒N bond forming reactions.[1] In particular, catalysts derived from
transition metals, such as Cu,[2] Pd,[3] Ni,[4] and Fe[5] have received special attention to
synthetic chemists. However, the development of new metal free protocol for C‒N bond
forming reaction is an interesting area of research. In continuation of our effort on the
metal-free amination process,[6] we report herein our preliminary result on the use of
a new nitrene source for amination of boronic acid without using any metal catalyst
(Scheme 1).
CONTACT Prodeep Phukan
pphukan@yahoo.com
Department of Chemistry, Gauhati University, Guwahati,
Assam 781 014, India.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
© 2018 Taylor & Francis

2
M. J. SARMA AND P. PHUKAN
Scheme 1. Synthesis of secondary amines via coupling of tosyltriazene and boronic acid.
Results and discussion
N-Tosylhydrazone is an important reagent used for different organic transformations,
such as Shapiro reaction[7] and Bamford–Stevens reaction.[8] It has also been well
known as an excellent carbene source.[9] Till date, a number synthetic chemist used
N-tosylhydrazone as an effective carbene source in different organic transformations.[7–9]
In this respect, a notable contribution was made by Barluenga et al.[10] by developing a base
promoted carbene transfer protocol for C‒C bond forming process using N-tosylhydrazone
(Scheme 2).
In analogy to this carbene source, we intended to develop an amine source, i.e.,
=
PhN NNHTs, which is structurally similar to the well-established reagent
N-tosylhydrazone with an intention to generate a catalyst free C‒N bond forming process.
=
PhN NNHTs was synthesized by diazotization of aniline followed by coupling of
p-tosylamide (Scheme 3).[11] After isolation, the product (PhN NNHTs) was dried under
=
vacuum for 4 h, followed by keeping in a desiccator over P2O5 for a day. The formation
1
of PhN NNHTs was further confirmed with the help of H NMR, 13C NMR, and mass
=
spectral analysis.
After having the triazene in hand, we intended to examine the efficacy of the compound
for C‒N bond forming reaction in presence of a boronic acid. To begin with, a coupling
reaction of tosyl–triazene was performed using phenyl boronic acid as model substrate
=
under different reaction conditions (Table 1). Initially, the synthesized PhN NNHTs
(1 mmol) was treated and phenyl boronic acid (1.5 mmol) at 110 °C in 1,4-dioxane
(2 mL) in presence of K2CO3 (1.5 mmol) in a Schlenk flask under nitrogen atmosphere.
Unfortunately, after 24 h of reaction, p-toluolsulfonamide was isolated as a major product
along with a mixture of unidentifiable products. On screening a number of different bases
we observed that mild bases such as K2CO3, Cs2CO3, etc. are ineffective in producing the
desired product. Thereafter, the reaction was examined in presence of KOH, DBU,
NaOtBu, and KOtBu. Although, the use of KOH was not found fruitful, other bases could
produce promising result. The reaction was further examined using different solvents such
as dioxane, ethyl acetate, THF, n-octane, and toluene. These experiments revealed that
nonpolar and aprotic solvents were effective for this transformation. We observed that it
is necessary to maintain dry atmosphere for achieving better result. Hence, the reaction
was reexamined using a combination of base and 4 Å molecular sieve which helped us
to improve the performance of the reaction. Finally a maximum yield of 70% of the desired
Scheme 2. C-C bond forming process using N-tosylhydrazone and boronic acid.

SYNTHETIC COMMUNICATIONS®
3
Scheme 3. Synthesis of N-tosyltriazene.
diphenylamine was recorded with DBU (3 equiv.) and 4 Å molecular sieve (0.25 g) in
toluene at 110 °C (Table 1, entry 21) which was considered as optimum reaction condition.
After optimizing the reaction condition, we have expanded the periphery of the reaction
by considering other boronic acids for the synthesis of different N-substituted anilines.
Results are summarized in Table 2. In general, moderate yields of N-substituted anilines
=
were obtained with 1 equiv. of PhN NNHTs, 1.5 equiv. of boronic acid and 3 equiv. of
DBU in presence of 4 Å molecular sieve in toluene at 110 °C. Aromatic boronic acids bear-
ing functional groups such as –CH3, –OMe, –Br, –Cl, and –NO2 all reacted successfully to
produce the corresponding N-substituted anilines (Table 2) in moderate yields irrespective
of the substituent position on the aromatic ring. This reaction works with aliphatic
boronic acids such as cyclohexyl boronic acid (Table 2, entry 10) with a similar reactivity
pattern.
Table 1. Optimization of reaction condition.
Entry
Base
A:B:C
Solvent
Temperature (°C)
Time (h)
Yield (%)
1
2
K2CO3
1:1.5:1.5
1:2:2
1,4-Dioxane
Toluene
Ethyl acetate
1,4-Dioxane
1,4-Dioxane
Toluene
Toluene
1,4-Dioxane
Toluene
110
MW (350 W)
80
36
20 min
24
–
K2CO3
–
3
K2CO3
1:1.5:2
1:1.0:2
1:1.5:1.5
1:1.5:2
1:1.5:1.5
1:1.5:1.5
1:1.5:2
1:1.5:1.5
1:1.5:3
1:1.5:1.5
1:1.5:1.5
1:1.5:2
1:1.5:3
1:1.5:4
1:1.5:3
1:1.5:1.5
1:1.5:3
1:1.5:3
1:1.5:3
–
4
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
KOH
110
24
–
5
110
24
–
6
R.T
24
–
7
110
24
–
8
110
36
–
9
NaOtBu
KOtBu
120
24
39
48
54
33
42
48
59
54
35
50
56
50
70
64
59
38
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
1,4-Dioxane
1,4-Dioxane
Ethyl acetate
Toluene
110
24
KOtBu
110
24
KOtBu
80
24
KOtBu
110
18
KOtBu
Toluene
110
24
KOtBu
Toluene
110
24
KOtBu
Toluene
110
24
KOtBu
Toluene
110
24
DBU
Toluene
110
24
DBU
Toluene
110
24
DBU
Toluene
120
24
DBU/4 Å MS
KOtBu/4 Å MS
DBU/4 Å MS
DBU/4 Å MS
Toluene
110
24
1:1.5:3
1:1.5:2
1:1.5:2
Toluene
110
24
n-Octane
n-Octane
140
24
Reflux
24
Bold values indicate the optimum reaction condition.
Reaction condition: Reactions were performed in 1 mmol scale; 2 mL of solvent was used.

4
M. J. SARMA AND P. PHUKAN
=
Table 2. Amination reaction of boronic acid and PhN NNHTs.
Entry
1
RB(OH)2
Product
Yield (%)
70
2
3
68
70
4
5
72
67
6
7
66
65
8
9
68
65
63
10
=
Reaction condition: PhN NNHTs (1 mmol), boronic acid (1.5 mmol), DBU (3 mmol), 0.25 g 4 Å MS, toluene (2 mL) 110 °C,
24 h; yields reported are isolated yield after chromatographic purification.

SYNTHETIC COMMUNICATIONS®
5
Conclusion
In conclusion, a novel process has been developed for the formation of C‒N bond using a
new amine source for the synthesis of secondary amines. The amine source p-toluenesulfonyl-
phenyltriazene reacts with boronic acid in presence of a base such as DBU and 4 Å
molecular sieve in toluene at 110 °C to generate secondary amine. This process works
under metal-free condition without using any catalyst to produce N-substituted aniline
in moderate yield. Further work in this area is in progress.
Experimental
All reagents and starting materials were purchased from commercial sources. Solvents were
dried before use and for secondary amines synthesis all reactions were performed in a
Schlenk flask under nitrogen atmosphere. IR spectra were recorded in IR Affinity-1
1
(Shimadzu) spectrometer. H NMR and 13C NMR spectra were recorded in Bruker
Ultrashield 300 NMR spectrometer. Chemical shifts are given in δ units relative to the
TMS signal as an internal reference in CDCl3. Coupling constants (J) were reported in
hertz.
=
Synthesis of PhN NNHTs
To a stirred solution of 12N HCl (2 mL) in water (8 mL), aniline (7.5 mmol) was added and
the mixture was cooled to 0 °C. To this mixture, NaNO2 solution (9 mmol in 2 mL of H2O)
was added slowly dropwise followed by slow addition of CH3COONa solution (26 mmol
in 5 mL water). The reaction mixture was allowed to stir for 1 h at 0 °C. Thereafter,
p-tosylamine (7.5 mmol) was added to this mixture at 0 °C and stirred for another hour
at 0 °C followed by stirring at room temperature for next hour. The resultant yellow
precipitate was filtered using Buchner funnel, washed with distilled water, dried under
vacuum for 4 h, followed by drying in desiccator over P2O5 at low temperature for
=
1 day and finally isolated yellow solid of PhN NNHTs.
3-[(4-Methylphenyl)sulfonyl]-1-phenyltriaz-1-ene
Yellow solid (1.838 g, 89% yield); IR (KBr, cm−1): υ 3250, 1630, 1595, 1450, 1375, 1329,
1
1302, 1256, 1137, 1057, 927, 847, 817, 727, 668; H NMR (300 MHz, CDCl3): δ 7.88
(m, 4H), 7.52–7.38 (m, 2H), 7.30 (d, J ¼ 8.4 Hz, 2H), 6.96 (d, J ¼ 9 Hz, 1H), 5.08
(br, 1H), 2.42 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 149.6, 143.5, 139.0, 129.7, 128.9,
126.4, 125.1, 122.2, 114.6, 21.5; MS (ES) m/z 275 [M, 100]; Anal. Calcd. for C13H13N3O2S
(%): C, 56.71; H, 4.76; N, 15.26. Found: C, 56.94; H, 4.52; N, 15.39.
General procedure for the synthesis of amines
=
To a mixture of PhN NNHTs (1 mmol), boronic acid (1.5 mmol) 4 Å MS (0.25 g) and
freshly distilled DBU (3 mmol), dry toluene (2 mL) was added in a Schlenk flask under
nitrogen atmosphere. The tube was caped tightly and heated at 110 °C for 24 h. After
completion of reaction, water was added to the reaction mixture and extracted with EtOAc.
The EtOAc layer was separated, washed with brine, dried over Na2SO4, and evaporated.
Purification of the crude product by flash chromatography over silica gel (230–400 mesh)
with petroleum ether–EtOAc as eluent gave the pure product.

6
M. J. SARMA AND P. PHUKAN
Funding
Financial support from SERB (DST), India (Grant No. EMR/2016/007883) is gratefully acknowledged.
References
[1] (a) Yudin, A. K.; Hartwig, J. F. Catalyzed Carbon-Heteroatom Bond Formation; Wiley-VCH:
Weinheim, 2010; (b) Corbet, J.-P.; Mignani, G. Chem. Rev. 2006, 106, 2651–2710; (c) Monnier,
F.; Taillefer, M. Angew. Chem., Int. Ed. 2009, 48, 6954–6971; (d) Beccalli, E. M.; Broggini, G.;
Martinelli, M.; Sottocornola, S. Chem. Rev. 2007, 107, 5318–5365; (e) Hartwig, J. F. Nature
2008, 455, 314–322; (f) Surry, D. S.; Buchwald, S. L. Angew. Chem., Int. Ed. 2008, 47,
6338–6361; (g) Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev. 2008, 108, 3054–3131;
(h) Allen, S. E., Walvoord, R. R., Padilla-Salinas, R.; Kozlowski, M. C. Chem. Rev. 2013,
113, 6234–6458.
[2] (a) Ullmann, F. Ueber eine neue Bildungsweise von Diphenylaminderivaten. Ber. Dtsch. Chem.
Ges. 1903, 36, 2382–2384; (b) Goldberg, I. Ueber Phenylirungen bei Gegenwart von Kupfer als
Katalysator. Ber. Dtsch. Chem. Ges. 1906, 39, 1691–1692; (c) Beletskaya, I. P.; Cheprakov, A. V.
Copper in Cross-coupling Reactions: The Post-Ullmann Chemistry. Coord. Chem. Rev. 2004,
248, 2337–2364; (d) Cristau, H. J.; Cellier, P. P.; Spindler, J.-F.; Taillefer, M. Highly Efficient
and Mild Copper-Catalyzed N- and C-Arylations with Aryl Bromides and Iodides. Chem.
Eur. J. 2004, 10, 5607–5622; (e) Chan, D. M. T.; Monaco, K. L.; Wang, R.-P.; Winters, M. P.
New N- and O-Arylations with Phenylboronic Acids and Cupric Acetate. Tetrahedron Lett.
1998, 39, 2933–2936; (f) Lam, P. Y. S.; Clark, C. G.; Saubern, S.; Adams, J.; Winters, M. P.;
Chan, D. M. T.; Combs, A. New Aryl/Heteroaryl C-N Bond Cross-Coupling Reactions via
Arylboronic acid/Cupric Acetate Arylation. Tetrahedron Lett. 1998, 39, 2941–2944; (g) Qiao,
J. X.; Lam, P. Y. Copper-promoted Carbon–heteroatom bond Cross-coupling with Boronic
Acids and Derivatives. Synlett, 2011, 2011, 829–856; (h) Roy, S.; Sarma, M. J.; Kashyap, B.;
Phukan, P. A quick Chan–Lam C–N and C–S Cross Coupling at Room Temperature in the
Presence of Square Pyramidal Cu(DMAP)4I]I as a Catalyst. Chem. Commun. 2016, 52,
1170–1173; (i) Collman, J. P.; Zhong, M. An Efficient Diamine Copper Complex-catalyzed
Coupling of Arylboronic Acids with Imidazoles. Org. Lett. 2000, 2, 1233–1236; (j) Shafir, A.;
Lichtor, P. A.; Buchwald, S. L. N- versus O-Arylation of Aminoalcohols: Orthogonal Selectivity
in Copper-Based Catalysts. J. Am. Chem. Soc. 2007, 129, 3490–3491; (k) Fructos, M. R.;
Trofimenko, S,; Díaz-Requejo, M. M.; Pérez, P. J. Facile Amine Formation by Intermolecular
Catalytic Amidation of Carbon-Hydrogen Bonds. J. Am. Chem. Soc. 2006, 128, 11784–11791;
(l) Cao, C.; Lu, Z.; Cai, Z.; Pang, G.; Shi, Y. Cheap Cu(I)/Hexamethylenetetramine (HMTA)
Catalytic System for C-N Coupling Reactions. Synth. Commun. 2012, 42, 279–284; (m) Antilla,
J. C.; Buchwald, S. L. Copper-Catalyzed Coupling of Arylboronic Acids and Amines. Org. Lett.
2001, 3, 2077–2079; (n) Moon, S.-Y.; Nam, J.; Rathwell, K.; Kim, W.-S. Copper-Catalyzed
Chan–Lam Coupling between Sulfonyl Azides and Boronic Acids at Room Temperature.
Org. Lett. 2014, 16, 338–341; (o) Kwong, F. Y.; Buchwald, S. L. Mild and Efficient Copper-
Catalyzed Amination of Aryl Bromides with Primary Alkylamines. Org. Lett., 2003, 5, 793–796;
(p) Klapars, A.; Huang, X.; Buchwald, S. L. A General and Efficient Copper Catalyst for the
Amidation of Aryl Halides, J. Am. Chem. Soc. 2002, 124, 7421–7428; (q) Evano, G.; Blanchard,
N. Eds. Copper-Mediated Cross-Coupling Reactions; John Wiley & Sons: New York, 2013.
[3] (a) Bariwal, J.; Van der. Eycken, E. C–N Bond Forming Cross-coupling Reactions: An
Overview. Chem. Soc. Rev. 2013, 42, 9283–9303; (b) Gildner, P. G.; Colacot, T. J. Reactions
of the 21st Century: Two Decades of Innovative Catalyst Design for Palladium-Catalyzed
Cross-Couplings. Organometallics, 2015, 34, 5497–5508; (c) Ruiz-Castillo, P.; Buchwald, S. L.
Applications of Palladium Catalyzed C–N Cross-Coupling Reactions. Chem. Rev., 2016, 116,
12564–12649; (d) Guram, A. S.; Rennels, R. A.; Buchwald, S. L. A Simple Catalytic Method
for the Conversion of Aryl Bromides to Arylamines. Angew. Chem. Int. Ed. 1995, 34,
1348–1350; (e) Iglesias, Á.; Álvarez, A.; de Lera, Á. R.; Muňiz, K. Palladium-catalyzed
Intermolecular C(sp3)-H amidation. Angew. Chem. Int. Ed. 2012, 51, 2225–2228;

SYNTHETIC COMMUNICATIONS®
7
(f) Kamikawa, K.; Sugimoto, S.; Uemura, M. Palladium-Catalyzed Amination of Aryl Bromides
Utilizing Arene-Chromium Complexes as Ligands. J. Org. Chem. 1998, 63, 8407–8410;
(g) Schön, U.; Messinger, J.; Prabhu, M. S.; Konda, A. An improved Synthesis of N-aryl and
N-heteroaryl Substituted Piperidones. Tetrahedron Lett. 2007, 48, 2519–2525; (h) Schwarz, N.;
Tillack, A.; Alex, K.; Sayyed, I. A.; Jackstell, R.; Beller, M. A Novel Palladium Catalyst for the
Amination of Electron-Rich Indole Derivatives. Tetrahedron Lett. 2007, 48, 2897–2900.
[4] (a) Cramer, R.; Coulson, D. R. Nickel-Catlyzed Displacement Reactions of Aryl Halides. J. Org.
Chem. 1975, 40, 2267–2273; (b) Matsubara, K.; Ueno, K.; Koga, Y.; Hara, K. Nickel−NHC-Cat-
alyzed α-Arylation of Acyclic Ketones and Amination of Haloarenes and Unexpected Preferen-
tial N-Arylation of 4-Aminopropiophenone. J. Org. Chem. 2007, 72, 5069–5076; (c)
Raghuvanshi, D. S.; Gupta, A. K.; Singh, K. N. Nickel-Mediated N-Arylation with Arylboronic
Acids: An Avenue to Chan–Lam Coupling. Org. Lett. 2012, 14, 4326–4329; (d) Corcoran, E. B.;
Pirnot, M. T.; Lin, S.; Dreher, S. D.; DiRocco, D. A.; Davies, I. W.; Buchwald, S. L.; MacMillan,
D. W. C. Aryl Amination Using Ligand-Free Ni(II) Salts and Photoredox Catalysis. Science,
2016, 353, 279–283.
[5] (a) Shang, R.; Ilies, L.; Nakamura, E. Iron-Catalyzed C-H Bond Activation. Chem. Rev., 2017,
117, 9086–9139; (b) Ghorai, S. K.; Gopalsamuthiram, V. G.; Jawalekar, A. M.; Patre, R. E.;
Pal, S. Iron-Catalyzed C-N Bond Formation. Tetrahedron, 2017, 73, 1769–1794;
(c) Hatakeyama, T.; Imayoshi, R.; Yoshimoto, Y.; Ghorai, S. K.; Jin, M.; Takaya, H.;
Norisuye, K.; Sohrin, Y.; Nakamura, M. Iron-Catalyzed Aromatic Amination for
Nonsymmetrical Triarylamine Synthesis. J. Am. Chem. Soc. 2012, 134, 20262–20265.
[6] Borah, A. J.; Phukan, P. Chem. Commun. 2012, 48, 5491–5493.
[7] Adlington, R. M.; Barrett, A. G. M. Acc. Chem. Res. 1983, 16, 55–59.
[8] Creary, X. Org. Synth. 1986, 64, 207.
[9] (a) Fulton, J. R.; Aggarwal, V. K.; de Vicente, J. Eur. J. Org. Chem. 2005, 2005, 1479–1492;
(b) Aggarwal, V. K.; De Vicente, J.; Bonnert, R. V. Org. Lett. 2001, 3, 2785–2788; (c) Aggarwal,
V. K.; Alonso, E.; Fang, G.; Ferrara, M.; Hynd, G.; Porcelloni, M. Angew. Chem. Int. Ed. 2001,
40, 1430–1433; (d) Xiao, Q.; Xia, Y.; Li, H.; Zhang, Y.; Wang, J. Coupling of N-Tosylhydrazones
with Terminal Alkynes Catalyzed by Copper(I): Synthesis of Trisubstituted Allenes. Angew.
Chem. Int. Ed. 2011, 50, 1114–1117; (e) Yao, T.; Hirano, K.; Satoh, T.; Miura, M. Nickel-
and Cobalt-Catalyzed Direct Alkylation of Azoles with N-Tosylhydrazones Bearing
Unactivated Alkyl Groups. Angew. Chem. Int. Ed. 2012, 51, 775–779.
[10] Barluenga, J.; Tomás-Gamasa, M.; Aznar, F.; Valdés, C. Nat. Chem. 2009, 1, 494–499.
[11] (a) Dutt, P. K.; Whitehead, R. H.; Wormall, A. The Action of Diazo-Salts on Aromatic
Sulfonamide. J. Chem. Soc., Trans. 1921, 119, 2088–2094; (b) Kumar, R. K.; Ali, M. A.;
Punniyamurthy, T. Org. Lett. 2011, 13, 2102–2105.