Synthesis and Spectroscopic Study of New 1H-1-Alkyl-6-methyl-7-nitroso-3-phenylpyrazolo[5,1-c][1,2,4]triazoles

Burcă, Ion; Badea, Valentin; Bercean, Vasile-Nicolae; Péter, Francisc

doi:10.3390/M1815

Open AccessCommunication

Synthesis and Spectroscopic Study of New 1H-1-Alkyl-6-methyl-7-nitroso-3-phenylpyrazolo[5,1-c][1,2,4]triazoles

by

Ion Burcă

,

Valentin Badea

^*

,

Vasile-Nicolae Bercean

and

Francisc Péter

Department of Applied Chemistry and Organic and Natural Compounds Engineering, Politehnica University Timisoara, Vasile Pârvan 6 Blvd., 300223 Timisoara, Romania

^*

Author to whom correspondence should be addressed.

Molbank 2024, 2024(2), M1815; https://doi.org/10.3390/M1815

Submission received: 9 March 2024 / Revised: 18 April 2024 / Accepted: 19 April 2024 / Published: 24 April 2024

(This article belongs to the Collection Heterocycle Reactions)

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Abstract

:

The nitrosation of 1H-1-alkyl-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazoles leads to new 1H-1-alkyl-6-methyl-7-nitroso-3-phenylpyrazolo[5,1-c][1,2,4] triazoles that react in acidic media, giving rise to 1H-1-alkyl-7-hydroxyimino-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazolium salts. These compounds were characterized by FT-IR, UV-Vis, ¹H-NMR, ¹³C-NMR, and ¹⁵N-NMR spectroscopic techniques.

Keywords:

nitrosation; 7-nitrosopyrazolo[5,1-c][1,2,4]triazole; 1H-1-alkyl-7-hydroxyimino-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazolium salts

1. Introduction

Compounds derived from pyrazolo[5,1-c][1,2,4]triazoles are used in photosensitive color materials, inks, and toners [1,2,3,4], as well as in other areas of interest [5,6,7,8]. To the best of our knowledge, there is limited available literature, excluding patent literature, on the synthesis and properties of these compounds [9,10].

Given the above, our aim is to increase knowledge on the synthesis and physicochemical properties of the pyrazolo[5,1-c][1,2,4]triazole heterocyclic pyrazolo[5,1-c][1,2,4] triazole system [11,12].

Previously, we have shown [12] that the nitrosation of 1H-6-methyl-3-phenylpyrazolo [5,1-c][1,2,4]triazole leads to the nitroso derivative (1a), which is as stable as its tautomer 1H-7-hydroxyimino-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazole (1b), as seen below in Scheme 1.

The scope of the current work is to extend the study on the nitrosation reaction of 1-alkylated (2a–c) derivatives of the 1H-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazole synthesized previously by our research group [13].

2. Results and Discussion

The nitrosation of 1H-1-alkyl-3-phenyl-6-methylpyrazolo[5,1-c][1,2,4]triazoles (2a–c) was performed in a similar way to the nitrosation of 1H-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazole [12], using sodium nitrite in aqueous hydrochloric acid, as seen below in Scheme 2.

In the first step, a pale yellow hydrochloride of the 1H-1-alkyl-6-methyl-7-nitroso-3-phenylpyrazolo[5,1-c][1,2,4]triazole is formed, which forms blue-colored nitroso derivatives (3a–c) after precipitation in water. The conclusion is that at high dilution, water is a stronger base than that of 3a–c triazoles in their oxime tautomer form.

The presence of the nitroso chromophore was confirmed by UV-Vis spectra, in which the compounds 3a–c had the maximum absorption wavelength, as follows: λ_max = 562 nm (3a), 558 nm (3b), and 563nm (3c). These values are specific to aromatic nitroso compounds.

For all compounds in the ¹H-NMR spectrum, the absence of a signal at 5.6 ppm can be observed, which corresponds to the proton bound to the carbon atom at the 7-C position of 1H-1-alkyl-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazole [12].

In the 2D NMR ¹H-¹³C HMBC and, respectively, ¹H-¹⁵N HMBC spectra of compounds 3a–c, we can observe long-range correlations between protons and carbon atoms and respective correlations between protons and nitrogen atoms over two or three bonds. These long-range correlations observed through the corresponding cross peaks in the 2D NMR HMBC spectra (Table 1) confirm the structures of the synthesized compounds.

However, compounds 3a–c do not exhibit one of the characteristic reactions of the N=O group grafted onto an aromatic heterocycle, namely condensation with aniline in an acetic acid medium at reflux (Scheme 3), a reaction that is shown in the literature for nitrosopyrazoles [14].

The lack of aniline reactivity, together with the fact that nitroso derivatives 3a–c change color from blue to yellow when dissolving in acetic acid or a hydrochloric acid/methanol mixture, suggests that pyrazolotriazolium salts are formed. We propose as possible structures for these salts the structures 5a–c, in which the nitroso chromophore no longer exists; see Scheme 4.

In support of the proposed structures, 5a–c, are the λ_max values from the UV-Vis spectra in acetic acid and methanolic HCl solution (Table 2), in which the characteristic absorption of the aromatic N=O chromophore around 560 nm is hypsochromically shifted to lower values of around 520 nm in acetic acid and around 340 nm in methanolic hydrochloric acid solution, respectively.

3. Materials and Methods

The chemical reagents were purchased from commercial sources (Merck, Darmstadt, Germany, and Fluka, Buchs, Switzerland) and used in the syntheses as received. The 1H-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazole, the 1H-1-alkyl-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazoles (2a–c), and the 1H-6-methyl-7-nitroso-3-phenylpyrazolo[5,1-c][1,2,4]triazole (1a) were prepared according to methods in the literature [1,11,12,14].

Melting points were measured on a Böetius PHMK apparatus (Veb Analytik, Dresden, Germany) and were uncorrected. A TLC analysis was performed on 60 F254 silica gel plates from Merck using benzene-ethyl acetate = 1:1 (v/v) as eluent. IR spectra were recorded on a Jasco FT/IR-410 spectrophotometer (Jasco Corporation, Tokyo, Japan) in KBr pellets. The ¹H-NMR and ¹³C-NMR spectra were recorded on a Bruker Avance III 500 MHz spectrometer (Billerica, USA). Chemical shifts (δ) were measured in ppm and coupling constants (J) in Hz. TMS was used as an internal standard. The elemental analysis was performed at the “Iuliu Hațieganu” University of Medicine and Pharmacy in Cluj-Napoca.

4. Experimental Section

4.1. General Synthesis Procedure

To a cooled solution (0 °C) of the 1H-1-alkyl-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazole (0.5 g, 2.5 mmol) in 30 mL of concentrated HCl and 100 mL of distilled water, a 30% sodium nitrite solution (2.75 mmol) was added dropwise under stirring. After 30 min of stirring at 0 °C and then 5 h at room temperature, a viscous suspension was formed. Then, the suspension was poured over 200 mL of water, and the obtained precipitate was separated by vacuum distillation. The compound was recrystallized from 96% ethanol [13].

4.2. 1,6-Dimethyl-7-nitroso-3-phenylpyrazolo[5,1-c][1,2,4]triazole (3a)

Blue-colored powder; isolation yield: 89%; melting point: 199–201 °C; FT-IR [cm⁻¹]: 2944, 2879, 1594, 1509, 1484, 1030, 1070; UV-Vis: λ_max [nm]: 561.55, ε [M⁻¹∙cm⁻¹]: 63.6; ¹H NMR (CDCl₃, 500 MHz) δ (ppm): 8.34–8.32 (m, 2H, 2’-H, 6’-H), 7.56–7.54 (m, 3H, 3’-H, 4’-H, 5’-H), 4.32 (s, 3H, 1-N-CH₃), 3.04 (6-C-CH₃); ¹³C NMR (CDCl₃, 125 MHz) δ (ppm): 164.2 (6-C), 144.9 (7-C), 140.4 (3-C), 134.8 (7a–C), 131.4 (4’-C), 129.1 (3’-C, 5’-C), 127.1 (2’-C, 6’-C), 123,8 (1’-C), 40.6 (1-N-CH₃), 13.4 (6-C-CH₃); ¹⁵N NMR (CDCl₃, 50 MHz) δ (ppm): 168.6 (1-N), 263.5 (5-N), 288.4 (2-N); Anal. Calcd for C₁₂H₁₁N₅O: C, 59.74; H, 4.60; N, 29.03. Found: C, 59.54; H, 4.37; N, 28.89. (Figures S1–S6)

4.3. 1-Ethyl-6-methyl-7-nitroso-3-phenylpyrazolo[5,1-c][1,2,4]triazole (3b)

Blue-colored powder; isolation yield: 82%; melting point: 172–174 °C; FT-IR [cm⁻¹]: 2982, 2935, 1696, 1584, 1505, 1485, 1444, 1371, 772, 736, 691; UV-Vis: λ_max [nm]: 558, ε [M⁻¹∙cm⁻¹]: 65.1; ¹H NMR (CDCl₃, 500 MHz) δ (ppm): 8.34–8.33 (m, 2H, 2’-H, 6’-H), 7.54–7.53 (m, 3H, 3’-H, 4’-H, 5’-H), 4.70 (q, 2H, J = 7.2 Hz, 1-N-CH₂-CH₃), 3.03 (6-C-CH₃), 1.50 (t, 3H, J = 7.2 Hz, 1-N-CH₂-CH₃); ¹³C NMR (CDCl₃, 125 MHz) δ (ppm): 164.2 (6-C) 145.0 (7-C), 140.4 (3-C), 133.9 (7a–C), 131.3 (4’-C), 129.0 (3’-C, 5’-C), 127.1 (2’-C, 6’-C), 124.0 (1’-C), 49.2 (1-N-CH₂-CH₃), 16.2 (1-N-CH₂-CH₃), 13.4 (6-C-CH₃); ¹⁵N NMR (CDCl₃, 50 MHz) δ (ppm): 183.5 (1-N), 263.5 (5-N), 286.0 (2-N); Anal. Calcd for C₁₃H₁₃N₅O: C,61.17; H, 4.136; N, 26.56. Found: C, 61.09; H,5.11; N, 27.22. (Figures S7–S13).

4.4. 1-Benzyl-6-methyl-7-nitroso-3-phenylpyrazolo[5,1-c][1,2,4]triazole (3c)

Blue-colored powder; isolation yield: 81%; melting point: 185–190 °C; FT-IR [cm⁻¹]: 2953, 2928, 1572, 1485, 1456, 767, 727, 692; UV-Vis: λ_max [nm]: 563.1, ε [M⁻¹∙cm⁻¹]: 56.4; ¹H NMR (CDCl₃, 500 MHz) δ (ppm): 8.33–8.31 (m, 2H, 2′-H, 6′-H), 7.52–7.51 (m, 3H, 3′-H, 4′-H, 5′-H), 7.41–7.40 (m, 2H, 2″-H, 6″-H); 7.33–7.28 (m, 3H, 3″-H, 4″-H, 5″-H), 5.79 (s, 2H, 1-N-CH₂-), 3.04 (6-C-CH₃); ¹³C NMR (CDCl₃, 125 MHz) δ (ppm): 164.2 (6-C), 145.0 (7-C), 140.7 (3-C), 134.8 (1″-C), 133.9 (7a–C), 131.4 (4′-C), 129.0 (3′-C, 5′-C, 3″-C, 5″-C), 128.9 (2″-C, 6″-C), 128.6 (2′-C, 6′-C), 127.2 (4″-C), 123.9 (1′-C), 57.1 (1-N-CH₂-), 13.4 (6-C-CH₃); ¹⁵N NMR (CDCl₃, 50 MHz) δ (ppm): 181.6 (1-N), 264.4 (5-N), 286.5 (2-N); Anal. Calcd for C₁₈H₁₅N₅O: C, 68.13; H, 4.76; N, 22.07. Found: C,68.05; H, 4.69; N, 21.89. (Figures S14–S20).

5. Conclusions

The nitrosation of 1H-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazoles leads to 1H-7-hydroxyimino-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazoles, while the nitrosation of 1H-1-alkyl-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazoles gives rise to 1H-1-alkyl-6-methyl-7-nitroso-3-phenylpyrazolo[5,1-c][1,2,4]triazoles. The tendency of these compounds to exist in the form of hydroxyimino is highlighted by the fact that even in a weakly acidic environment, the nitroso aromatic group no longer shows the characteristic properties of reactions or color. This is the reason that we proposed their existence in solution in the form of 1-{1H-1-alkyl-7-hydroxyimino-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]}triazolium salts.

Supplementary Materials

Figure S1 1H NMR spectrum of the compound (3a), Figure S2 13C NMR spectrum of the compound (3a), Figure S3 HSQC 1H-13C spectrum of the compound (3a), Figure S4 HMBC 1H-13C spectrum of the compound (3a), Figure S5 HMBC 1H-15N spectrum of the compound (3a), Figure S6 FT-IR spectrum of the compound (3a), Figure S7 1H NMR spectrum of the compound (3b), Figure S8 13C NMR spectrum of the compound (3b), Figure S9 COSY 1H-1H spectrum of the compound (3b), Figure S10 HMBC 1H-13C spectrum of the compound (3b), Figure S11 1H-13C spectrum of the compound (3b), Figure S12 HMBC 1H-15N spectrum of the compound (3b), Figure S13 FT-IR spectrum of the compound (3b), Figure S14 1H NMR spectrum of the compound (3c), Figure S15 13C NMR spectrum of the compound (3c), Figure S16 COSY 1H-1H spectrum of the compound (3c), Figure S17 HMBC 1H-13C spectrum of the compound (3c), Figure S18 1H-13C spectrum of the compound (3c), Figure S19 HMBC 1H-15N spectrum of the compound (3c), Figure S20 FT-IR spectrum of the compound (3c).

Author Contributions

Designed the experiments, V.B.; performed the experiments, I.B. and V.-N.B.; analyzed the spectral data, V.B. and F.P.; wrote the manuscript, I.B. and V.-N.B.; supervision, F.P. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

The data presented in this study are available within the article or Supplementary Materials.

Conflicts of Interest

The authors declare no conflicts of interest.

References

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Scheme 1. Nitroso-hydroxyimino tautomerism of 1H-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazole derivative.

Scheme 2. The nitrosation of 1H-1-alkyl-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazoles (2a–c).

Scheme 3. Reaction of 1H-1-alkyl-6-methyl-7-nitroso-3-phenylpyrazolo[5,1-c][1,2,4]triazoles (3a–c) with aniline.

Scheme 4. 1H-1-alkyl-7-hydroxyimino-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazolium salt (5a–c) formation.

Table 1. Experimental 2D NMR correlation data for compounds 3a–c.

Compound	HMBC Long-Range Correlations
Compound	¹H-¹³C (ppm)	¹H-¹⁵N (ppm)
3a	6-C-CH₃ (3.04) → 6-C (164.2)	6-C-CH₃ (3.04) → 5-N (263.5)
	6-C-CH₃ (3.04) → 7-C (145.0)	1-N-CH₃ (4.32) → 1-N (168.6)
	1-N-CH₃ (4.32) → 7a-C (133.9)	1-N-CH₃ (4.32) → 2-N (288.4)
3b	1-N-CH₂CH₃ (1.50) → 1-N-CH₂CH₃ (49.2)	1-N-CH₂CH₃ (1.50) → 1-N (183.5)
	6-C-CH₃ (3.03) → 7-C (145.0)	6-C-CH₃ (3.03) → 5-N (263.5)
	6-C-CH₃ (3.03) → 6-C (164.2)	1-N-CH₂CH₃ (4.70) → 1-N (183.5)
	1-N-CH₂CH₃ (4.70) → 1-N-CH₂CH₃ (16.3)	1-N-CH₂CH₃ (4.70) → 2-N (286.0)
	1-N-CH₂CH₃ (4.70) → 7a-C (133.9)
3c	6-C-CH₃ (3.04) → 7-C (145.0)	6-C-CH₃ (3.04) → 5-N (264.4)
	6-C-CH₃ (3.04) → 6-C (164.2)	1-N-CH₂ (5.79) → 1-N (181.6)
	1-N-CH₂ (5.79) → 7a-C (133.9)	1-N-CH₂ (5.79) → 2-N (286.5)
	1-N-CH₂ (5.79) → 1″-C (134.8)
	1-N-CH₂ (5.79) → 2″-H, 6″-H (7.41–7.40)

Table 2. UV-VIS absorption maxima of compounds 3a–c.

R	λ_max [nm], ε [M⁻¹∙cm⁻¹] (CH₃OH)	λ_max [nm] (CH₃COOH)	λ_max [nm] (HCl/CH₃OH)
-CH₃	561.5, 63.6	519	339.5
-C₂H₅	558.0, 65.1	518.5	340.5
-CH₂C₆H₅	563.0, 56.4	522	343

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Burcă, I.; Badea, V.; Bercean, V.-N.; Péter, F. Synthesis and Spectroscopic Study of New 1H-1-Alkyl-6-methyl-7-nitroso-3-phenylpyrazolo[5,1-c][1,2,4]triazoles. Molbank 2024, 2024, M1815. https://doi.org/10.3390/M1815

AMA Style

Burcă I, Badea V, Bercean V-N, Péter F. Synthesis and Spectroscopic Study of New 1H-1-Alkyl-6-methyl-7-nitroso-3-phenylpyrazolo[5,1-c][1,2,4]triazoles. Molbank. 2024; 2024(2):M1815. https://doi.org/10.3390/M1815

Chicago/Turabian Style

Burcă, Ion, Valentin Badea, Vasile-Nicolae Bercean, and Francisc Péter. 2024. "Synthesis and Spectroscopic Study of New 1H-1-Alkyl-6-methyl-7-nitroso-3-phenylpyrazolo[5,1-c][1,2,4]triazoles" Molbank 2024, no. 2: M1815. https://doi.org/10.3390/M1815

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Synthesis and Spectroscopic Study of New 1H-1-Alkyl-6-methyl-7-nitroso-3-phenylpyrazolo[5,1-c][1,2,4]triazoles

Abstract

1. Introduction

2. Results and Discussion

3. Materials and Methods

4. Experimental Section

4.1. General Synthesis Procedure

4.2. 1,6-Dimethyl-7-nitroso-3-phenylpyrazolo[5,1-c][1,2,4]triazole (3a)

4.3. 1-Ethyl-6-methyl-7-nitroso-3-phenylpyrazolo[5,1-c][1,2,4]triazole (3b)

4.4. 1-Benzyl-6-methyl-7-nitroso-3-phenylpyrazolo[5,1-c][1,2,4]triazole (3c)

5. Conclusions

Supplementary Materials

Author Contributions

Funding

Data Availability Statement

Conflicts of Interest

References

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