2022 Volume 5 Issue 5

Open Access

INEOS OPEN, 2022, 5 (5), 130–132  Journal of Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences Download PDF DOI: 10.32931/io2223a

Synthesis of (E)-2-Cyano-5-phenylpent-2-en-4-ynoic Acid Esters and N-Substituted Amides

Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, str. 1, Moscow, 119334 Russia
 

Corresponding author: I. A. Khotina, e-mail: khotina@ineos.ac.ru
Received 27 March 2023; accepted 19 May 2023

Abstract

(E)-2-Сyano-5-phenylpent-2-en-4-ynoic acid esters and N-substituted amides were synthesized by the Knoevenagel condensation of 3-phenylpropiolaldehyde with the corresponding cyanoacetates or cyanoacetamides in the presence of basic alumina used as a catalyst. The IR and Raman spectra of the resulting compounds show strong absorption bands in the range of 1565–1580 cm^–1 which are attributed to the vibrations of the C=C bond in the enyl moiety.

Key words: phenylpropiolaldehyde, (E)-2-cyano-5-phenylpent-2-en-4-ynoic acid esters and N-substituted amides, basic alumina, Knoevenagel condensation.

 

Introduction

The derivatives of 2-cyanoacrylic acid are of particular interest owing to their potential biological activity and great synthetic opportunities, especially in the field of heterocyclic and polymer chemistry [1–3].

A large variety of cyanoacrylic acid derivatives have been synthesized to date. For example, the Knoevenagel condensation was used to obtain the derivatives of cyanoacrylic acid bearing carbazole units, which, owing to the formation of hydrogen bonds, exhibit variable fluorescence properties in solvents, water, and alcohols, as well as in the presence of metal ions and can be used as fluorescent labels in chemosensors [4].

However, fluorescent 3-ethynylphenyl derivatives of 2-cyanoacrylic acid have not been described, except for the 3-ethynylphenyl derivative of 2-cyanoacrylic acid N-phenylamide, which, according to the results of XRD analysis, features planar arrangement of the acetylene and vinylene groups in the central conjugated moiety [5, 6].

Results and discussion

A series of (E)-2-cyano-5-phenylpent-2-en-4-ynoic acid esters (1) and N-substituted amides (2) were obtained by the Knoevenagel condensation of phenylpropiolaldehyde with the corresponding cyanoacetates or cyanoacetamides in the presence of Al₂O₃ used as a catalyst (Scheme 1) [7–9].

Scheme 1

The use of a heterogeneous catalyst, namely, basic alumina [10] allows for reducing the contribution of side processes. The structures and compositions of compounds 1 and 2 were unambiguously confirmed by elemental analysis, IR, Raman, and NMR spectroscopy. The yields and selected physicochemical characteristics of the resulting products are presented in Table 1.

Table 1. Yields and selected physicochemical characteristics of compounds 1 and 2

Comp.	Yield, %	Mp, °С	Elemental analyses (found/calcd)			Formula
			С	Н	N
1а	76	69–70	73.85 73.92	4.34 4.29	6.58 6.63	C13H9NO2
1b	78	73–74	74.62 74.65	4.90 4.92	6.24 6.22	C14H11NO2
1c	80	47–48	75.86 75.93	4.61 4.67	5.87 5.90	C15H11NO2
1d	82	86–87	76.78 76.59	3.78 3.85	5.81 5.95	C15H9NO2
1e	75	68–69	79.95 79.76	9.36 9.32	3.28 3.32	C28H39NO2
2a	67	108–110	74.22 74.27	4.78 4.79	13,25 13.33	C13H10N2O
2c	64	104–105	76.10 76.22	5.02 5.11	11.67 11.85	C15H12N2O
2f	65	179–180	79.41 79.31	4.31 4.44	10.10 10.29	C18H12N2O
2g	72	132–134	73.37 73.46	4.13 4.11	14.32 14.28	C12H8N2O
2h	68	65–66	77.13 77.25	5.98 6.10	10.54 10.60	C17H16N2O

Similar IR and Raman spectra of α,β-unsaturated esters 1 and amides 2 (Table 2) show the expected characteristic intensive absorption bands (IR) and weak lines (Raman) of С=О stretches (1735–1720 cm^–1) for esters 1 as well as amide I (1675–1660 cm^–1) and amide II (1540–1530 cm^–1) bands for amides 2. Of special interest is the assignment of absorption bands of C≡C and C≡N stretches [11] and a strong band in the range of 1565–1580 cm^–1, which is not observed in the IR spectra of 2-cyanocinnamates [12], the derivatives of phenylacetylene [13] and methyl (E)-5-phenylpent-2-en-4-ynoate [14].

Table 2. IR/Raman spectroscopic data for compounds 1 and 2

Comp.	IR bands/Raman lines, n/cm–1
	Ph	C=O	C≡N	C≡C	C=C	Other peaks
1а	1597	1734	2230	2193	1575	–
1b	1599	1731	2230	2188/ 2189	1579/ 1571	–
1c	1598	1727	2220	2185/ 2189	1576/ 1574	1647 (=CH2)
1d	1600	1736	2227	2189/ 2193	1576/ 1570	3293 (ºCH)
1e	1599	1721	2235	2195	1575	–
2a	1600	1662	2222	2187/ 2185	1565/ 1565 1583/ 1581	3305, 3380 (NH) 1538 Amide II
2c	1600	1666	2222	2190	1569/ 1566	1641 (=CH2), 3279 (NH) 1534 Amide II
2f	1596	1661	2224	2192/ 2194	1569/ 1566	3251 (NH) 1527 Amide II
2g	1600	1674	2220	2187	1569	3451, 3458 (NH) 1613 Amide II
2h	1600	1664	2219	2192	1568	–

The optimal geometry, vibration frequencies, and IR intensities for E- and Z-isomers of Ph–C≡C–CH=C(CN)–COOMe (1a) were calculated by the DFT-B3LYP functional method with the standard 6-31G(d,p) basis using the Gaussian-98 software package [15]. According to the results obtained, the E-isomer appeared to be more stable than its Z-counterpart by ~3.5 kcal/mol. Thus, Ph–C≡C–CH=C(CN) moiety in 1a is planar.

Of note is satisfactory agreement between the calculated and experimental values both in terms of the band frequencies (Dν < 30 cm^–1) and intensities (qualitatively).

A weak band at 2225 ± 10 cm^–1 in the IR and Raman spectra of compounds 1 and 2 was attributed to vibrations of the C≡N bond and falls into the region of ν(СN) of α,β-unsaturated alkyl nitriles. The absorption bands of C≡C bond vibrations in the IR and Raman spectra had high intensity and low frequency and appeared at 2190 ± 5 cm^–1. The intense absorption band at 1565–1580 cm^–1 is mainly associated with vibrations of the C7=C8 bond, which kinematically interacts with the phenyl core when the C≡C bond is completely neutral.

Two absorption bands of ν(С=С) and ν(NH) in the IR and Raman spectra of compound 2a are likely to correspond to two conformers that differ in the twist angle between the phenyl ring and the central moiety of the molecule [16].

The carbon signals in the ¹³С NMR spectra were assigned based on the closely related results of HMBC experiments for 1a and 2a. The NMR spectrum of 1a showed intense correlation peaks between the =CH proton signal and the carbon resonances at 111.3 ppm and 113.7 ppm as well as its weak cross-peak with the ¹³C signal at 114.2 ppm, which weakly interacts with the methyl protons. Therefore, the mentioned signals refer to C5, C9, and C8 carbon nuclei. The signal of C6 carbon nucleus was observed at 85.2 ppm. Similar assignments were made for compound 2a.

Hence, the Knoevenagel condensation of phenylpropiolaldehyde on the surface of basic alumina can readily afford (E)-5-phenyl-2-cyanopent-2-en-4-ynoic acid esters and amides.

Experimental section

General remarks

The IR spectra of solid samples were recorded on a Perkin-Elmer 1725-FTIR spectrometer equipped with a Perkin-Elmer Diffuse Reflectance (PEDR) accessory and a modified sample holder. The FT-Raman spectra were measured on a Perkin-Elmer Raman Station 400 dispersive Raman spectrometer equipped with an InGaAs detector (operating range 3500–200 cm^–1) at a resolution of 4 cm^–1 with Nd:YAG laser excitation (1064 nm). The NMR spectra were registered on a Bruker AMX-400 instrument (400.26 MHz (¹H), 100.68 MHz (¹³C)) in acetone-d₆.

Syntheses

General procedure for the synthesis of esters 1. In the case of compounds 1а–c, 1e, a solution of 0.01 mol of 3-phenylpropiolaldehyde in 0.012 mol of the corresponding alkyl cyanoacetate was stirred with 3 g of basic Al₂O₃ (pH = 9.5) until the exothermic effect ceased and the mass solidified. The reaction mixture was left at 20 °C for 12 h and then extracted with dichloromethane. The solvent was removed under vacuum. The resulting residue was crystallized from hexane. The synthesis of compound 1d was carried out upon addition of 3 mL of absolute dioxane using 6 g of Al₂O₃.

Methyl (E)-2-cyano-5-phenylpent-2-en-4-ynoate (1a). ¹H NMR: δ 3.90 (s, 3H, ОMe), 7.37–7.61 (m, 5H, H_Ar), 7.54 (s, 1H, =CH) ppm. ¹³C NMR: δ 53.4 (OMe), 85.2 (C6), 111.3 (C5), 113.7 (С≡N), 114.2 (C8), 120.6 (C1), 128.6 (C3 and C3'), 131.0 (C4), 132.8 (C2 and C2'), 136.8 (=CH), 161.45 (C=O) ppm.

Ethyl (E)-2-cyano-5-phenylpent-2-en-4-ynoate (1b). ¹H NMR: δ 1.34 (t, 3H, Me, J = 7.2 Hz), 4.35 (q, 2H, OCH₂, J = 7.2 Hz), 7.50–7.65 (m, 5H, H_Ar), 7.67 (s, 1H, =CH) ppm.

Allyl (E)-2-cyano-5-phenylpent-2-en-4-ynoate (1c). ¹H NMR: δ 4.81 (d, 2H, OCH₂, J = 5.6 Hz), 5.30 (dd, 1H, cis-H in =CH₂, J = 1.4/11.2 Hz), 5.43 (dd, 1H, trans-H in =CH₂, J = 1.4/13.2 Hz), 6.03 (m, 1H, =CH (All)), 7.50–7.65 (m, 5H, H_Ar), 7.71 (s, 1H, =CH) ppm.

Propargyl (E)-2-cyano-5-phenylpent-2-en-4-ynoate (1d). ¹H NMR: δ 3.19 (t, 1H, ≡CH, J = 5.6 Hz), 4.96 (d, 2H, OCH₂, J = 5.6 Hz), 7.50–7.66 (m, 5H, H_Ar), 7.73 (s, 1H, =CH) ppm.

Hexadecyl (E)-2-cyano-5-phenylpent-2-en-4-ynoate (1e). ¹H NMR: δ 0.88 (t, 3H, Me, J = 7.2 Hz), 3.97 (q, 2H, OCH₂, J = 7.2 Hz), 7.42–7.55 (m, 5H, H_Ar), 7.28 (s, 1H, =CH) ppm.

General procedure for the synthesis of amides 2. A solution of 0.01 mol of 3-phenylpropiolaldehyde and 0.01 mol of the corresponding cyanoacetamide in 3 mL of dry N-methylpyrrolidone (NMP) was stirred with 5 g of basic Al₂O₃ until the exothermic effect ceased and the mass solidified. The reaction mixture was left at 20 °C for 12 h and then extracted with NMP. The resulting solution was poured into water. The precipitate obtained was collected by filtration and recrystallized from a toluene–hexane mixture.

(E)-2-Cyano-N-methyl-5-phenylpent-2-en-4-ynamide (2a). ¹H NMR: δ 2.90 (q, 3H, Me, J = 4.8 Hz), 7.47–7.62 (m, 7H, 5H_Ar + =СH + NH) ppm. ¹³C NMR: δ 27.0 (NMe), 85.2 (C6), 109.0 (C5), 118.1 (C8), 115.7 (C9), 120.8 (C1), 128.5 (C3 and C3'), 130.6 (C4), 132.6 (C2 and C2'), 134.2 (C7), 159.4 (C=O) ppm.

(E)-2-Cyano-N-allyl-5-phenylpent-2-en-4-ynamide (2c). ¹H NMR: δ 4.20 (m, 2H, CH₂NH), 5.24 (m, 2H, cis- and trans-H in =CH₂), 5.87 (m, 1H, =CH (All)), 6.30 (br. s, 2H, NH) 7.37–7.60 (m, 5H, H_Ar), 7.57 (s, 1H, =CH) ppm.

(E)-2-Cyano-N-phenyl-5-phenylpent-2-en-4-ynamide (2f). ¹Н NMR: δ 7.18–7.77 (m, 10Н, Н_Ar) 7.69 (s, 1H, =CH), 9.43 (br. s, 1H, NH) ppm.

(E)-2-Cyano-5-phenylpent-2-en-4-ynamide (2g). ¹H NMR: δ 6.30 (br. s, 2H, NH₂), 7.44–7.65 (m, 5H, H_Ar), 7.67 (s, 1H, =CH) ppm.

(E)-5-Phenyl-2-(piperidine-1-carbonyl)pent-2-en-4-ynenitrile (2h). ¹Н NMR: δ 1.66 (br. s) and 3.58 (m) (10Н, piperidyl), 7.35–7.57 (m, 5H, H_Ar), 7.08 (s, 1H, =CH) ppm.

Conclusions

(E)-2-Cyano-5-phenylpent-2-en-4-ynoic acid esters and N-substituted amides were obtained by the Knoevenagel condensation between 3-phenylpropiolaldehyde and the corresponding cyanoacetates or cyanoacetamides in the presence of basic alumina used as a catalyst. The new esters and amides were characterized by the NMR, IR, and Raman spectra, as well as elemental analysis.

Acknowledgements

This work was performed with financial support from the Ministry of Science and Higher Education of the Russian Federation using the equipment of the Center for Molecular Composition Studies of INEOS RAS (agreement no. 075-03-2023-642).

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