3,4-Diaminopyridine-2,5-dicarbonitrile

Abstract

Pyridines fused with heterocyclic rings are of great interest as both photovoltaic materials and biologically active compounds. The most convenient precursors for these compounds are pyridine-2,3-diamines. In this communication, 3,4-diaminopyridine-2,5-dicarbonitrile was synthesized by the reaction of 2,5-dibromo-3,4-diaminopyridine with copper cyanide; the best yield of the target compound was achieved by heating the reaction mixture in N,N-dimethylformamide at 120 °C for 6 h. The structure of the newly synthesized compound was established by means of elemental analysis, high resolution mass-spectrometry, ¹H, ¹³C NMR, IR, UV spectroscopy and mass-spectrometry.

1. Introduction

1,2-Diamine moiety in benzene or heterocyclic rings is often used to design fused 1,2,5-thia(selena)diazoles [1,2,3,4], quinoxalines [5], pyridopyrazines [6] and related scaffolds, which are of great interest in the construction of various photovoltaic materials, i.e., organic solar cells (OSCs), organic light-emitting diodes (OLEDs), organic field effect transistors (OFETs) and others [7,8,9,10,11,12]. Cyano derivatives of fused 1,2,5-chalcogenadiazoles are less explored, but are highly promising precursors for these applications. They can be prepared from hardly available ortho-diaminoheterocycles, containing cyano substituents. The synthesis of 2,5-dibromo-3,4-diaminopyridine 1 was recently reported [13]. Meanwhile, the substitution reactions of this compound are limited by the Sonogashira cross-coupling reaction [14]. Cyanation of aryl and hetaryl halides is an important and useful transformation in organic synthesis. The most common method for the cyanation of these compounds has been the reaction of aryl halides with metal cyanides [15]; in a number of cases, palladium [16] or copper [17] catalysis was successfully employed. Herein, we report the synthesis of 3,4-diaminopyridine-2,5-dicarbonitrile 2 by the cyanation of 2,5-dibromo-3,4-diaminopyridine 1.

2. Results and Discussion

An analysis of the literature data showed that copper(I) cyanide [18,19], or more rarely sodium cyanide [20], was used to replace the bromine atom in 2-bromopyridines with a cyano group. The study of the substitution reaction of the bromine atom in the pyridine ring for the cyano group was carried out with copper and potassium cyanide in ethanol and N,N-dimethylformamide (DMF). It was shown that the nature of the reagents, solvents, as well as the temperature of the reaction mixture significantly affected the course of the chemical transformation (Scheme 1).

It was found that diamine 1 did not react with potassium and copper cyanides by refluxing in ethanol (

Table 1. Reaction of 2,5-dibromo-3,4-diaminopyridine 2 with metal cyanides (2.2 equiv).

Entry	Solvent	Reagent	Temperature, °C	Time, h	Yield of 2, %
1	EtOH	KCN	78	10	0
2	EtOH	CuCN	78	10	0
3	DMF	KCN	25	8	0
4	DMF	KCN	60	8	0
5	DMF	CuCN	25	8	0
6	DMF	CuCN	60	8	0
7	DMF	KCN	100	8	0
8	DMF	CuCN	100	8	traces
9	DMF	KCN	120	8	0
10	DMF	CuCN	140	8	40
11	DMF	CuCN	140	10	39

, entries 1,2). The replacement of ethanol by polar aprotic DMF significantly affected the course of the chemical reaction. We showed by thin layer chromatography (TLC) that potassium cyanide did not react with diamine 1 both at room temperature and when heated in DMF (entries 3,4,7,9). However, the replacement of potassium cyanide with copper cyanide, with a careful temperature control, made it possible to obtain the target cyanide 2 in a moderate yield (entry 10). An increase in the time of chemical transformation did not lead to an increase in the yield of target product 2 (entry 11).

The structure of 3,4-diaminopyridine-2,5-dicarbonitrile 2 was confirmed by means of elemental analysis, high resolution mass-spectrometry, ¹H, ¹³C NMR, IR and UV spectroscopy, and mass-spectrometry.

In conclusion, it was shown that the cyanation of 2,5-dibromo-3,4-diaminopyridine 1 gave dicyanoderivative 2, which can be considered as a possible precursor for the preparation of pyrido-1,2,5-chalcogenadiazoles, which may be of interest as compounds with useful physical properties.

3. Materials and Methods

2,5-Dibromo-3,4-diaminopyridine 1 was prepared according to the published method [13]. The solvents and reagents were purchased from commercial sources and used as received. Elemental analysis was performed on a 2400 Elemental Analyzer (Perkin ElmerInc., Waltham, MA, USA). The melting point was determined on a Kofler hot-stage apparatus and is uncorrected. ¹H and ¹³C NMR spectra were taken with a Bruker AM-300 machine (Bruker AXS Handheld Inc., Kennewick, WA, USA) (at frequencies of 300 and 75 MHz) in DMSO-d₆ solution. The IR spectrum was measured with a Bruker “Alpha-T” instrument (Santa Barbara, CA, USA) in a KBr pellet. The high-resolution MS spectrum was measured on a Bruker micrOTOF II instrument (Bruker Daltonik Gmbh, Bremen, Germany) using electrospray ionization (ESI). Solution UV–visible absorption spectra were recorded using an OKB Spektr SF-2000 UV/Vis/NIR spectrophotometer (St. Petersburg, Russia) controlled with SF-2000 software (St. Petersburg, Russia). The sample was measured in a 1 cm quartz cell at room temperature with a 1.1 × 10⁻⁷ mol/mL concentration in acetone.

• Synthesis of 3,4-diaminopyridine-2,5-dicarbonitrile 2 (Supplementary Materials).

A mixture of 2,5-dibromo-3,4-diaminopyridine 1 (200 mg, 0.75 mmol), CuCN (148 mg, 1.65 mmol) in dry DMF (5 mL) was heated at 140 °C in a sealed vial with stirring for 6 h. On completion (monitored by TLC), the mixture was filtered through Celite, washed with hot EtOAc (3 × 30 mL), and concentrated under deep reduced pressure. The residue was subjected to column chromatography on silica gel (Silica gel Merck 60, eluent: EtOAc–CH₂Cl₂, 1:5, v/v). Yield 47 mg (40%), white solid, mp = > 250 °C, R_f = 0.1 (CH₂Cl₂). IR spectrum, ν, cm^–1: 3394, 3366, 3250, 2235 (CN), 1694, 1648, 1584, 1518, 1233, 921. ¹H-NMR (ppm): δ 7.82 (s, 1H), 7.14 (s, 2H), 6.16 (s, 2H). ¹³C-NMR (ppm): δ 145.8, 142.2, 137.1, 117.5, 116.6, 113.5, 91.5. HRMS (ESI-TOF), m/z: calcd for C₇H₆N₅ [M + H]⁺, 160.0618, found, 160.0622. MS (EI, 70eV), m/z (I, %): 160 ([M + 1]⁺, 7), 159 ([M]⁺, 100), 132 (10), 105 (12), 78 (9), 52 (3), 28 (5). UV-Vis spectra (in acetone), λ_max: 356 nm (ε 5041 M⁻¹ cm⁻¹). Anal. calcd. for C₇H₅N₅ (159.0352): C, 52.83; H, 3.17; N, 44.01. Found: C, 52.80; H, 3.13; N, 43.9%.