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Department of Industrial Chemistry “Toso Montanari”, Alma Mater Studiorum-Università di Bologna, Viale del Risorgimento 4, 40136 Bologna, Italy
Authors to whom correspondence should be addressed.
Molbank 2020, 2020(3), M1154;
Received: 21 July 2020 / Revised: 4 August 2020 / Accepted: 17 August 2020 / Published: 20 August 2020
(This article belongs to the Section Organic Synthesis)


The compound 1,1’,1’’-(2’,4’-dinitro-[1,1’-biphenyl]-2,4,6-triyl)tripiperidine was synthesized by SEAr/SNAr reaction between 1-fluoro-2,4-dinitrobenzene and 1,3,5-tris(N-piperidinyl)benzene. The structure of the newly synthesized compound was elucidated based on 1H-NMR, 13C-NMR, ESI-MS, UV-Vis and IR spectroscopy.
Keywords: SNAr; SEAr; 1,3,5-tris(N-piperidinyl)benzene; 1-fluoro-2,4-dinitrobenzene SNAr; SEAr; 1,3,5-tris(N-piperidinyl)benzene; 1-fluoro-2,4-dinitrobenzene

1. Introduction

Aromatic substitution reaction (both SNAr [1,2] and SEAr [3,4]) is one of the most important reactions in organic chemistry. In particular, the combination between aromatic electrophiles and nucleophiles at the neutral carbon atom allows one to obtain highly conjugated architectures bearing both electron donor and acceptor moieties. This kind of compound is receiving growing attention in material chemistry fields, such as solar energy conversion [5] and optoelectronic devices [6].
In the past, we reported several studies about this kind of reaction, mainly by coupling supernucleophiles such as 1,3,5-triaminobenzenes with different aromatic electrophiles [7,8,9,10,11]. Here, we report the synthesis of 1,1’,1’’-(2’,4’-dinitro-[1,1’-biphenyl]-2,4,6-triyl)tripiperidine in mild conditions by the combination of 1-fluoro-2,4-dinitrobenzene (1) with 1,3,5-tris(N-piperidinyl)benzene (2). The product obtained may be of interest as a precursor for the hair-dyeing sector, since it is possible to reduce the two nitro groups to amino groups and to obtain a biphenyldiamine derivative. Notably, the molecules that belong to this class of compounds are known for their ability to react with the keratin present in the hair [12].

2. Results

The synthesis of 1,1’,1’’-(2’,4’-dinitro-[1,1’-biphenyl]-2,4,6-triyl)tripiperidine (4) (Scheme 1) was performed by SEAr/SNAr reaction between 1-fluoro-2,4-dinitrobenzene (1) and 1,3,5-tripiperidinylbenzene (2) in acetonitrile at room temperature. The addition of triethylamine was made to prevent the protonation of reagent 2 by hydrofluoric acid, which is formed during the reaction course and would lead to a decrease in yield.
At the end of the reaction, the product was purified by column chromatography on silica gel using a n-hexane/ethyl acetate ratio of 9/1 as eluent (yield 60%). The structure of the newly synthesized compound was elucidated based on 1H-NMR, 13C-NMR, ESI-MS, IR, and UV/Vis spectroscopy (see spectra in Supplementary Materials).
The reaction course follows the classic SNAr mechanism; however, in reactions involving halonitrobenzenes, the ability of the latter to add nucleophiles is due to the activating effect of the nitro group, thus, nucleophiles should be able to add to these arenes also at positions occupied by hydrogen, subsequently resulting also in the formation of σH adducts [13]. This process is faster than the competing process of addition to the carbon atom bearing a nucleofugal group, resulting in the “classic” SNAr reaction. Moreover, only when the σH adduct cannot be transformed into the SNArH reaction product is the SNAr reaction observed [14], as in the current case.
It must be noted that Effenberger [15] reported that the reaction between 2 and 1-chloro-2,4-dinitrobenzene in 1:1 chloroform/ethanol at reflux did not occur. In the current case, the use of the more electrophilic fluoroderivative allowed us to obtain the novel compound, bearing contemporarily an electron donor and an electron acceptor moiety, which makes it of interest in the applied field as well as a potentially useful precursor in hair-dyeing technique.

3. Materials and Methods

The 1H and 13C spectra were recorded on a Mercury 400 (Varian, Palo Alto, CA, USA) spectrometer operating at 400 MHz (for 1H‐NMR) and at 100 MHz (for 13C‐NMR). Chemical shifts refer to the solvent for 1H and 13C‐NMR (δ = 7.26 ppm and δ = 77.0 ppm, respectively, for CDCl3). Signal multiplicities were established by Distortionless Enhanced by Polarization Transfer (DEPT) experiments. Chemical shifts were measured in δ (ppm). J values are given in Hertz. Electron spray ionization mass spectra (ESI-MS) were recorded with a WATERS ZQ 4000 instrument (Waters Corporation, Milford, MA, USA). IR spectrum were recorded with a Fourier transform spectrophotometer PerkinElmer FT-IR Spectrum Two (Perkin Elmer, Waltham, MA, USA) in the 4000−800 cm−1 wavelength range using a NaCl cell. UV/Vis spectrum was recorded using a Perkin Elmer Lamba 12 spectrophotometer. Chromatographic purifications (FC) were carried out on glass columns packed with Merck (Merck & Co. Readington, NJ, USA) silica gel (Merck grade 9385, 230−400 Mesh particle size, 60 Å pore size) at medium pressure. Thin layer chromatography (TLC) was performed on silica gel60 F254 coated aluminum foils (Fluka, Buchs, Switzerland).
The compound 1,3,5-Tris(N-piperidinyl)benzene was synthesized according to literature [11]; 1-fluoro-2,4-dinitrobenzene was purchased from Sigma-Aldrich (Milan, Italy).

Synthesis of 1,1’,1’’-(2’,4’-Dinitro-[1,1’-biphenyl]-2,4,6-triyl)tripiperidine

In a round bottom flask, 1-fluoro-2,4-dinitrobenzene 1 (12.6 µL, 18.61 mg, 0.1 mmol) and 1,3,5-tris(N-piperidinyl)benzene 2 (32.7 mg, 0.1 mmol) were added and dissolved in acetonitrile (10 mL). Triethylamine (13.9 µL, 10.1 mg, 0.1 mmol) was added and the mixture was stirred at room temperature overnight. The reaction course was monitored by TLC (eluent hexane/ethyl acetate 9/1). The product was purified by chromatography column on silica gel (eluent hexane/ethyl acetate 9/1). The product yield was 29.6 mg, 60%.
Dark red solid, cubic crystals (recrystallized from CH3CN) m.p.: 240.4–241.2 °C; 1H-NMR (400 MHz, CDCl3, 25 °C) δ, ppm: 8.81 (d, J = 2.4 Hz, 1H), 8.36 (dd, J1 = 8.7 Hz, J2 = 2.4 Hz, 1H), 7.84 (d, J = 8.7 Hz, 1H), 6.42 (s, 2H), 3.22 (t, J = 5.6 Hz, 4H), 2.69–2.56 (m, 8H), 1.74–1.68 (m, 4H), 1.64–1.56 (m, 4,H), 1.40–1.27 (m, 10H); 13C‐NMR: (100 MHz, CDCl3, 25 °C) δ, ppm: 153.9, 152.7, 149.1, 145.3, 140.8, 136.2 (CH), 125.5 (CH), 119.6 (CH), 116.1, 102.9 (CH), 53.2 (CH2), 49.8 (CH2), 25.9 (CH2), 25.8 (CH2), 24.3 (CH2), 24.1 (CH2); FT-IR υ (cm−1): 3687, 3617, 320, 2398, 1942, 1598, 1524, 1432, 1224, 1208, 1046, 928; UV-Vis λmax = 473 nm; ε473 = 4228 L mol−1 cm−1; ESI-MS+ (m/z): 494 [M + H]+, 516 [M + Na]+, 532 [M + K]+; elemental analysis for C27H35N5O4, calculated C, 65.70; H, 7.15; N, 14.19; O, 12.96, found C, 65.73; H, 7.16; N, 14.17.

Supplementary Materials

The following are available online, Figure S1. 1H‐NMR spectrum in CDCl3 of compound 4; Figure S2. 13C‐NMR spectrum in CDCl3 of compound 4; Figure S3. DEPT spectrum in CDCl3 of compound 4; Figure S4. ESI-MS spectrum of compound 4; Figure S5. FT-IR spectrum of compound 4; Figure S6. UV/Vis spectrum of compound 4.

Author Contributions

Methodology: G.M., S.F. and D.T.; writing—original draft preparation: G.M. and C.B.; supervision and funding: C.B. All authors have read and agreed to the published version of the manuscript.


Alma Mater Studiorum, University of Bologna (RFO funds) funded this research.

Conflicts of Interest

The authors declare no conflict of interest


  1. Terrier, F. Modern Nucleophilic Aromatic Substitution; Wiley VCH: Weinheim, Germany, 2013. [Google Scholar]
  2. Terrier, F. Nucleophilic Aromatic Displacement; VCH: New York, NY, USA, 1991. [Google Scholar]
  3. Ouellette, R.J.; Rawn, J.D. Electrophilic aromatic substitution. In Organic Chemistry: Structure, Mechanism and Synthesis, 1st ed.; Elsevier: San Diego, CA, USA, 2014; Chapter 13; pp. 417–451. [Google Scholar]
  4. Ouellette, R.J.; Rawn, J.D. Electrophilic aromatic substitution. In Organic Chemistry: Structure, Mechanism and Synthesis, 2nd ed.; Elsevier: San Diego, CA, USA, 2018; Chapter 13; pp. 375–407. [Google Scholar]
  5. Hagfeldt, A.; Boschloo, G.; Sun, L.; Kloo, L.; Pettersson, H. Dye-sensitized solar cells. Chem. Rev. 2010, 110, 6595–6663. [Google Scholar] [CrossRef]
  6. He, G.S.; Tan, L.S.; Zheng, Q.; Prasad, P.N. Multiphoton absorbing materials:  Molecular designs, characterizations, and applications. Chem. Rev. 2008, 108, 1245–1330. [Google Scholar] [CrossRef]
  7. Boga, C.; Micheletti, G.; Cino, S.; Fazzini, S.; Forlani, L.; Zanna, N.; Spinelli, D. C–C coupling between trinitrothiophenes and triaminobenzenes: Zwitterionic intermediates and new all-conjugated structures. Org. Biomol. Chem. 2016, 14, 4267–4275. [Google Scholar] [CrossRef]
  8. Micheletti, G.; Boga, C.; Pafundi, M.; Pollicino, S.; Zanna, N. New electron-donor and -acceptor architectures from benzofurazans and sym-triaminobenzenes: Intermediates, products and an unusual nitro group shift. Org. Biomol. Chem. 2016, 14, 768–776. [Google Scholar] [CrossRef]
  9. Boga, C.; Cino, S.; Micheletti, G.; Padovan, D.; Prati, L.; Mazzanti, A.; Zanna, N. New azo-decorated N-pyrrolidinylthiazoles: Synthesis, properties and an unexpected remote substituent effect transmission. Org. Biomol. Chem. 2016, 14, 7061–7068. [Google Scholar] [CrossRef]
  10. Del Vecchio, E.; Boga, C.; Forlani, L.; Tozzi, S.; Micheletti, G.; Cino, S. Ring closure of azo compounds to 1,2-annulated benzimidazole derivatives and further evidence of reversibility of the azo-coupling reaction. J. Org. Chem. 2015, 80, 2216–2222. [Google Scholar] [CrossRef] [PubMed]
  11. Boga, C.; Del Vecchio, E.; Tozzi, S.; Forlani, L.; Monari, M.; Micheletti, G.; Zanna, N. First isolation of a Wheland intermediate in the azo-coupling reaction, its X-ray crystal structure determination and products from its evolution. ARKIVOC 2014, iv, 51–66. [Google Scholar]
  12. Chassot, L.; Braun, H.-J. Colouring Agents for Keratin Fibres Containing (1.1-biphenyl)-2,4-diamine Derivatives in Addition to Novel (1.1-biphenyl)-2,4-diamine-derivatives. U.S. Patent 2003/0172470 A1, 18 September 2003. [Google Scholar]
  13. Mąkosza, M. How does nucleophilic aromatic substitution in nitroarenes really proceed: General mechanism. Synlett 2017, 49, 3247–3254. [Google Scholar] [CrossRef]
  14. Błaziak, K.; Danikiewicz, W.; Mąkosza, M. How does nucleophilic aromatic substitution really proceed in nitroarenes? Computational prediction and experimental verification. J. Am. Chem. Soc. 2016, 138, 7276–7281. [Google Scholar] [CrossRef] [PubMed]
  15. Effenberger, F.; Agster, W.; Fischer, P.; Jogun, K.H.; Stezowski, J.J.; Daltrozzo, E.; Kollmannsberger-Von Nell, G. Synthesis, structure, and spectral behaviour of donor-acceptor substituted biphenyls. J. Org. Chem. 1983, 48, 4649–4658. [Google Scholar] [CrossRef]
Scheme 1. Synthesis of 1,1’,1’’-(2’,4’-dinitro-[1,1’-biphenyl]-2,4,6-triyl)tripiperidine.
Scheme 1. Synthesis of 1,1’,1’’-(2’,4’-dinitro-[1,1’-biphenyl]-2,4,6-triyl)tripiperidine.
Molbank 2020 m1154 sch001
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