Ethyl 4H-Pyran-4-one-2-carboxylate

Abstract

The title compound was characterised for the first time by ¹³C NMR, including the determination of CH coupling constants, and its X-ray structure was determined, showing double ribbons of molecules in the crystal held together by weak CH to O=C hydrogen bonds.

1. Introduction

The simple heterocyclic compound ethyl 4H-pyran-4-one-2-carboxylate (“ethyl comanate”) 4 was first mentioned in the literature in 1884 [1], and its convenient synthesis by the thermal decarboxylation of monoethyl chelidonate 3 was reported in 1885 [2]. The compound has recently been of interest in the synthesis of various fused-ring heterocyclic systems [3,4,5]. In the 140 years since its first preparation, it has been characterised using a range of spectroscopic techniques including UV, IR, and ¹H NMR spectroscopy [6] and photoelectron spectroscopy [7] and has also been the subject of detailed quantum chemical calculations [5]. However, as far as we are aware, its ¹³C NMR spectrum has never been reported and its X-ray structure has not been determined. In this paper, we report a detailed NMR study including the use of 2D methods leading to the complete assignment of the ¹H and ¹³C spectra, including C–H coupling constants and the X-ray structure determination of 4.

2. Results

We have recently been involved in high-level spectroscopic and theoretical studies on pyran-4-one 2 [8,9], and this has required its repeated large-scale preparation. This involves the synthesis of chelidonic acid 1 [10] through the base-induced condensation of diethyl oxalate with acetone followed by acid hydrolysis of the resulting diester and thermal decarboxylation [11] to afford 2 (Scheme 1). However, on some occasions, the vacuum distillation of the final product gave a second, higher-boiling component, which was identified as the ethyl ester 4. This can be attributed to the incomplete hydrolysis of the diester affording the monoester 3 in addition to 1, which, upon decarboxylation, gives 4.

The ¹H NMR spectrum of 4 (see Supplementary Material) was in good agreement with the literature data, which have been reported both in CDCl₃ [6] and in CD₃SOCD₃ [4]. The ¹³C NMR spectrum was recorded for the first time and, using HSQC, this could be correlated with the ¹H data, allowing complete assignment (

Table 1. ¹H and ¹³C chemical shifts (ppm) and H–H and C–H coupling constants (Hz) for 4.

Position
	δC	δH	3JH–H	4JH–H	1JC–H	2JC–H	3JC–H
2	152.8	–			–	8.4	4.0
3	119.9	7.11		2.4	172.3	–	3.8
4	178.4	–			–	7.1, 1.5	1.5
5	118.4	6.44	5.7	2.4	169.8	7.8	3.4
6	155.2	7.83	5.7		199.7	7.2	–
Ester CO	159.7	–			–	3.3, 3.3
CH2	62.9	4.43	7.2		149.2	4.45	–
CH3	13.9	1.41	7.2		127.5	2.6	–

, Figure 1), which was also fully supported by HMBC.

By recording the ¹³C NMR spectrum without ¹H decoupling, values for the C–H coupling constants were readily determined (Table 1). The value of ¹J_C–H in particular gives a measure of the hybridisation situation at each carbon [12]. It is interesting to note that the anomalously large value of 199.7 Hz observed for ¹J_C6–H6 compared to the smaller values of 169.8 and 172.3 Hz for ¹J_C5–H5 and ¹J_C3–H3 is in good agreement with the values of 199.5 and 168.8 Hz, respectively, observed for pyran-4-one 2 itself [13] and ²J_C5–H6 and ²J_C6–H5 at 7.8 and 7.2 Hz, respectively, which are also comparable to the corresponding values of 8.95 and 6.18 Hz observed for pyran-4-one. The values for J_C–H in various disubstituted pyran-4-ones [14] are also in agreement with those reported here for compound 4, but we have been unable to locate any previous such data for a monosubstituted pyran-4-one.

Compound 4, obtained by vacuum distillation, solidified directly to give suitable crystals, and we were able to determine the structure by X-ray diffraction. The molecular structure (Figure 2) features a completely planar heterocyclic ring with the ester C=O arranged anti to the ring C–O bond (torsion angle O(1)–C(2)–C(7)–O(7) 180.0°). The dimensions of the heterocyclic ring are summarised in

Table 2. Heterocyclic ring dimensions for 4 (Å, °).

Bond Lengths		Internal Angles
O(1)–C(2)	1.3629(17)	C(6)–O(1)–C(2)	117.02(11)
C(2)–C(3)	1.335(2)	O(1)–C(2)–C(3)	123.68(13)
C(3)–C(4)	1.458(2)	C(2)–C(3)–C(4)	120.75(14)
C(4)–O(4)	1.2339(19)	C(3)–C(4)–C(5)	113.93(13)
C(4)–C(5)	1.452(2)	C(4)–C(5)–C(6)	120.45(14)
C(5)–C(6)	1.332(2)	C(5)–C(6)–O(1)	124.18(13)
C(6)–O(1)	1.3653(18)

.

The crystal structure when viewed along the b-axis (Figure 3) consists of parallel planar ribbons formed by double rows of molecules linked by weak C(7)=O(7)···H(6)–C(6) hydrogen bonds and cross-linked by C(4)=O(4)···H(3)–C(3) hydrogen bonds with parameters within the conventional range (

Table 3. Hydrogen bonding parameters for 4 (Å, °).

D—H···A	D—H	H···A	D···A	D—H···A
C(3)–H(3)···O(4)	0.950	2.309	3.249	169.95
C(6)–H(6)···O(7)	0.950	2.351	3.116	137.15

). The structure consists of a series of such hydrogen-bonded planes perpendicular to the b-axis with a separation of 3.24 Å.

A search of the Cambridge Crystallographic Database (CSD) showed that only a few comparable structures have been determined before and, in fact, only two 2-monosubstituted pyran-4-ones have been located (Figure 4). The dioxocine substituted compound 5 [15] and the indolinone compound 6 [4] have very similar bond lengths and angles around the pyranone ring to 4 but show completely different intermolecular interactions, with head to tail dimers formed by a weak dioxocine C–H to O=C interaction in 5 and linear chains formed by N–H to pyranone O=C hydrogen bonding in 6.

In summary, we have been able to fully assign the ¹³C NMR spectrum for compound 4 for the first time and determine the C–H coupling constants. The X-ray structure of 4 features ribbons with two rows of molecules held together by weak C–H to O=C hydrogen bonding.

3. Experimental Section

3.1. General Experimental Details

Melting points were recorded using a Reichert hot-stage microscope (Reichert, Vienna, Austria) and are uncorrected. NMR spectra were obtained using a Bruker AV300 instrument (Bruker, Billerica, MA, USA). Spectra were run with internal Me₄Si as the reference, and chemical shifts are reported in ppm to high frequency of the reference. NMR spectra were processed using iNMR reader, version 6.3.3 (Mestrelab Research, Santiago de Compostela, Spain).

3.2. Formation of Ethyl 4H-Pyran-4-one-2-carboxylate 4

The preparation of chelidonic acid 1 was conducted according to the literature procedure [10] using sodium (6.44 g, 280 mmol), ethanol (160 mL), acetone (8.12 g, 140 mmol), and diethyl oxalate (42.0 g, 287.mmol). After neutralisation, the solid diester was filtered off and hydrolysed by boiling with concentrated HCl (45 mL) for 20 h. The crude chelidonic acid 1, contaminated by some monoester 3, was subjected to decarboxylation using the reported method [11] with copper powder and 1,10-phenanthroline in boiling tetralin. Extraction of the product followed by Kugelrohr distillation gave first pyran-4-one 2, bp₂₀ 100–110 °C, followed by the title ester 4, bp₂₀ 170–180 °C, as colourless crystals, mp 96–97 °C (lit. [16] 96–98 °C). ¹H NMR (300 MHz, CDCl₃) δ 7.83 (1H, d, J = 5.7 Hz, H-6), 7.11 (1H, d, J = 2.4 Hz, H-3), 6.44 (1H, dd, J = 5.7, 2.4 Hz, H-5), 4.43 (2H, q, J = 7.2 Hz, CH₂), 1.41 (3H, t, J = 7.2 Hz, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 178.4 (C-4), 159.7 (ester C=O), 155.2 (6-CH), 152.8 (2-C), 119.9 (3-CH), 118.4 (5-CH), 62.9 (CH₂), 13.9 (CH₃). For C–H coupling constants, see Table 1

3.3. X-Ray Structure Determination of 4

X-ray diffraction data for compound 4 were collected at 173 K using a Rigaku XtaLAB P200 diffractometer [Mo Kα radiation (λ = 0.71073 Å), Tokyo, Japan]. Structures were solved by dual-space methods (SHELXT-2018/2) [17] and refined by full-matrix least-squares against F² (SHELXL-2018/3) [18].

The crystal data for C₈H₈O₄ are as follows: M = 168.15 g mol^–1, colourless prism, crystal dimensions 0.10 × 0.05 × 0.05 mm, orthorhombic, space group Pnma (No. 62), a = 7.7844(7), b = 6.4742(6), c = 15.1151(14) Å, V = 761.77(12) ų, Z = 4, D_calc = 1.466 g cm^–3, T = 173 K, goodness of fit on F² 1.129, 4381 reflections measured, 763 unique (R_int = 0.0182), which were used in all calculations. The final R₁ [I > 2σ(I)] was 0.0313, and wR₂ (all data) was 0.0904. Data have been deposited at the Cambridge Crystallographic Data Centre as CCDC 2240572. The data can be obtained free of charge from the Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/structures (accessed on 23 November 2024).