Synthesis and Molecular Structures of the Lowest Melting Odd- and Even-Numbered α,β-Unsaturated Carboxylic Acids—(E)-Hept-2-Enoic Acid and (E)-Oct-2-Enoic Acid

Abstract

The molecular structures of the two lowest melting odd- and even-numbered α,β-unsaturated carboxylic acids—(E)-hept-2-enoic acid (C7) and (E)-oct-2-enoic acid (C8)—are herein reported. The title compounds were crystallized by slow evaporation of ethanolic solutions at −30 °C. C7 crystallizes in the triclinic space group $P\overline{1}$ with two molecules in the unit cell and C8 in the monoclinic space group C2/c with eight molecules in the unit cell. The unit cell parameters for C7 are: a = 5.3049(2) Å, b = 6.6322(3) Å, c = 11.1428(5) Å, α = 103.972(3)°, β = 97.542(3)°, γ = 90.104(3)°, and V = 376.92(3) ų (T = 150(2) K). The unit cell parameters for C8 are: a = 19.032(10) Å, b = 9.368(5) Å, c = 11.520(6) Å, β = 123.033(11)°, and V = 1721.80(16) ų (T = 200(2) K).

1. Introduction

Essential fatty acids have attracted much interest in food, health, and nutrition sciences due to their role in biological processes especially for humans [1,2,3,4]. Oleic acid, (Z)-octadec-9-enoic acid, and linoleic acid, (9Z,12Z)-9,12-octadecadienoic acid, respectively, can be found, for example, in meat and milk products, nuts, olives, and oils. Increasing the number of double bonds within the alkyl chain leads to a melting point decrease and hence yields liquids at ambient conditions, which is an especially important property of polyunsaturated fatty acids [5]. Derivatives of the title compounds—(E)-hept-2-enoic acid (C7) and (E)-oct-2-enoic acid (C8)—exhibit interesting occurrences and properties. For example, they can be found as active compounds in beetles’ sexual pheromones [6,7], as part of siderophores in bacteria [8,9], as an anti-osteoporotic [10], or as phytotoxic substances [11], respectively.

Crystal structure determinations of α,β-unsaturated carboxylic acids have been known from the literature in the cases of acrylic acid (C3) [12,13,14,15] and crotonic acid (C4) [16] for more than 40 years, but the crystal structures of other members of α,β-unsaturated carboxylic acids, namely, (E)-pent-2-enoic acid (C5) [17], (E)-hex-2-enoic acid (C6) [18], (E)-non-2-enoic acid (C9), (E)-dec-2-enoic acid (C10) [19], (E)-undec-2-enoic acid (C11) [20], and (E)-dodec-2-enoic acid (C12) [21], respectively, have just recently been reported. In addition, two crystal structure determinations of co-crystals containing C6 are also known [22,23]. In comparison, a complete set of crystal structures of the corresponding saturated carboxylic acids (propionic acid to pentadecanoic acid) is also available from the literature [24,25,26,27,28]. In this contribution, we report on the synthesis, characterization, and crystal structure determinations of the two missing and lowest melting odd- and even-numbered members of the series of α,β-unsaturated carboxylic acids—(E)-hept-2-enoic acid (C7) and (E)-oct-2-enoic acid (C8)—respectively, which complete the series of crystal structure data from C3 to C12.

2. Results and Discussion

2.1. Synthesis and Melting Points

The synthesis of α,β-unsaturated carboxylic acids has been known for more than 130 years, when Schneegans reported on the synthesis of nonenoic acid via the reaction of heptanal, sodium acetate, and acetic anhydride in 1885 [29]. More than 20 years later, Harding and Weizmann reported on the correct molecular formula of the received (E)-non-2-enoic acid in 1910 [30]. The syntheses of the two α,β-unsaturated carboxylic acids C7 and C8 were conducted by an adapted condensation reaction of malonic acid and the appropriate aldehyde at room temperature in high yields and purities as depicted in Scheme 1 [31,32,33,34] (see Experimental Section for details).

The title compounds exhibit low melting points, which lie below room temperature (C7: −11 °C; C8: 10 °C). As expected, crystallographic data of these structures have not yet been reported to date due to difficulties in crystallizing and analyzing. From the complete series of trans-α,β-unsaturated carboxylic acids, a melting point alternation for even- and odd-numbered trans-α,β-unsaturated carboxylic acids from C3 to C16 can be found as for most homologous chemical series. For comparison, in the case of saturated carboxylic acids, from hexanoic acid to pentadecanoic acid, this effect was traced back to crystal density variations [24]. This correlation was not detected in the present case for trans-α,β-unsaturated carboxylic acids from C3 to C16.

The melting point alternation for the series of trans-α,β-unsaturated carboxylic acids C3 to C16 based on melting points known from the literature and this work is depicted in Figure 1 [17,18,19,20,21,35,36,37,38,39,40]. It is clear that C7 has the lowest melting point within the series of odd-numbered carboxylic acids, whereas C8 exhibits the lowest melting point within the series of even-numbered carboxylic acids, respectively. Crystallographic density of C7 is significantly higher than that of C8, whereas the melting point of C7 is remarkably lower than that of C8, which is in contrast to the most homologous chemical series, e.g., for saturated carboxylic acids.

2.2. Crystal Structures

Molecular structures of linked acid dimers of the title compounds with pairs of O–H∙∙∙O hydrogen bonds are shown in Figure 2 and Figure 3, respectively, with an atom-labeling scheme and displacement thermal ellipsoids at the 50% probability level. Crystal and instrumental parameters of the crystal structure determinations of C7 and C8 can be found in

Table 1. Crystal data and structure refinement for C7 and C8.

Compound	C7	C8
Chemical formula	C7H12O2	C8H14O2
Formula weight	128.17	142.19
Crystal system	triclinic	monoclinic
a	5.3049(2) Å	19.032(10) Å
b	6.6322(3) Å	9.368(5) Å
c	11.1428(5) Å	11.520(6) Å
α	103.972(3)°	90°
β	97.542(3)°	123.033(11)°
γ	90.104(3)°	90°
Unit cell volume	376.92(3) Å3	1721.8(16) Å3
Temperature	150(2) K	200(2) K
Space group	$P\overline{1}$	C2/c
Z (Z’)	2 (1)	8 (1)
μ	0.661 mm−1	0.077 mm−1
No. of reflections measured	5233	13812
No. of independent reflections	1325	1883
Rint	0.0194	0.0293
Final R1 values (I > 2σ(I))	0.0299	0.0433
Final wR(F2) values (I > 2σ(I))	0.0837	0.1071
Final R1 values (all data)	0.0328	0.0634
Final wR(F2) values (all data)	0.0861	0.1238
Goodness of fit on F2	1.068	1.047
Density	1.129 g/cm3	1.097 g/cm3

.

Selected bond lengths and angles are summarized in

Table 2. Selected atom distances (Å) and angles (°) for C7 and C8.

Compound	C7	C8
Atoms	Distance	Distance
C1–O1	1.3178(12)	1.2655(18)
C1–O2	1.2265(12)	1.2644(18)
C1–C2	1.4672(15)	1.4712(19)
C2–C3	1.3240(15)	1.3140(20)
C3–C4	1.4905(15)	1.4920(20)
average C–C (alkyl chain)	1.519	1.519
H-bonds in:	D–H∙∙∙A	D∙∙∙A
C7	O1–H1∙∙∙O2i	2.637
C8	O1–H1∙∙∙O1ii	2.651 #
	O2–H2A∙∙∙O2ii	2.595 #
Atoms	Angle	Angle
O1–C1–O2	122.91(9)	122.36(13)
O1–C1–C2	113.37(9)	118.88(12)
O2–C1–C2	123.71(9)	118.76(13)
C1–C2–C3	121.41(9)	121.69(13)
C2–C3–C4	126.47(9)	127.87(13)
H-bonds in:	D–H∙∙∙A	Angle
C7	O1–H1∙∙∙O2i	176.8
C8	O1–H1∙∙∙O1ii	177.3 #
	O2–H2A∙∙∙O2ii	171.7 #
Symmetry codes:	(i) −x, −y, −z
	(ii) –x, y, –z + 2.5

Note: ^# suffered from disorder.

. C7 crystallizes in the triclinic space group $P\overline{1}$ with two molecules in the unit cell, whereas C8 crystallizes in the monoclinic space group C2/c with eight molecules in the unit cell. Trans-α,β-unsaturated carboxylic acids in the series C3–C12 crystallize either in orthorhombic (C3: Ibam) [12,13,14,15], monoclinic (C4: C2/c; C9: P2₁/c) [16,19], or triclinic (C5, C6, C10, C11, C12: $P\overline{1}$) [17,18,19,20,21] space groups. The title compounds show no exceptional behavior and crystallize in these known space groups (C7: $P\overline{1}$; C8: C2/c). Bond lengths and angles in C7 and C8 closely resemble values found in other α,β-unsaturated carboxylic acids [12,13,14,15,16,17,18,19,20,21,22,23]. The bond length C1–C2 is in accordance with reported C(sp²)–C(sp²) single bonds incorporated in carboxylic systems (C7: 1.4672(15) Å; C8: 1.4712(19) Å; ref.: 1.475 Å [41]). The bond lengths C2–C3 show characteristic values for C(sp²)–C(sp²) trans-configurated double bonds (C7: 1.3240(15) Å; C8: 1.3140(20) Å; ref.: 1.312 Å [41]). The crystal structures of C7 and C8 are characterized by carboxylic acid dimers linked by pairs of O–H∙∙∙O hydrogen bonds. Interestingly, the hydrogen-bonded dimer in C7 is connected by inversion (O1∙∙∙O2), whereas C8 exhibits a hydrogen-bonded dimer built up by a mirror plane (O1∙∙∙O1 and O2∙∙∙O2). Views of the packing of acid dimer layers in C7 and C8 are depicted in Figure 4 and Figure 5, respectively.

All non-hydrogen atoms of C7 and C8 lie nearly in one plane with a mean deviation from the best plane defined by these atoms of 0.02 Å in C7 and 0.03 Å in C8. In C7, C6 exhibits the largest deviation from that plane (0.033(1) Å), whereas this is observed for O2 with 0.056(1) Å in C8, respectively. For C8, the carboxyl group is affected by disorder. Equal C–O bond distances were obtained (C1–O1: 1.2655(18), C1–O2 1.2644(18) Å), which indicates that there is a half mirrored overlay by a single and a double bond for C1–O1 and C1–O2, respectively. This could not be further resolved reasonably by applying a splitting model and geometric restraints. The initial geometry of the carboxyl group was retained, and two hydrogen atoms (H1 and H2A) are therefore present, each only half occupied (O1–H1: 0.90(4), O2–H2A: 0.84(4) Å). Only one orientation is shown in each case for Figure 3.

3. Experimental Section

3.1. General Considerations

NMR spectra were recorded on a AV300 or AV400 spectrometer (Bruker, Billerica, MA, USA) and chemical shifts of the ¹H, and ¹³C spectra were reported in parts per million (ppm) using the solvent shifts for ¹H and ¹³C as internal standard (CDCl₃: ¹H δ = 7.26, ¹³C δ = 77.0). Elemental analysis for C and H was performed on a Microanalysator TruSpec CHNS device (LECO Corporation, Saint Joseph, MI, USA). MS spectra were determined by electron spray ionization using a Electron Finnigan MAT 95-XP mass spectrometer (Thermo Fisher Scientific, Waltham, MA, USA). Melting points were determined by cyclic differential scanning calorimetry (DSC) using a DSC823^e device (Mettler-Toledo GmbH, Gießen, Germany) in the range of −50 °C to 50 °C with a heating rate of 10 K/min (2 cycles, N₂ atmosphere, Al crucible). All melting points are peak temperatures.

3.2. Materials

All chemicals were used as received without further drying or purification unless otherwise noted. n-pentanal, n-hexanal, and malonic acid were purchased from ABCR (purity >98%).

3.3. General Synthesis and Crystallization of α,β-Unsaturated Carboxylic Acids

Malonic acid (25.0 g, 240.2 mmol, 1.0 eq) was dissolved in dry pyridine (38.0 g, 480.5 mmol, 2.0 eq) at room temperature in a three-necked flask equipped with a magnetic stir bar and a reflux condenser under a mild flow of argon. The appropriate aldehyde (240.2 mmol, 1.0 eq) was then added in one portion, and the resulting clear solution was further stirred for 72 h at room temperature under argon. Afterwards, the resulting light yellow to orange solution was brought to an acidic pH value by adding phosphoric acid at 0 °C (42.5 wt %, 138.5 g, 600.6 mmol, 2.5 eq). The resulting two layers were extracted three times with 150 mL portions of ethyl acetate and reduced to a volume of ca. 150 mL in vacuo. To remove impurities from aldol condensation the raw acid was converted into the corresponding sodium salt by addition of an aqueous solution of sodium carbonate (20.4 g, 192.2 mmol, 0.8 eq in 200 mL). After stirring for 30 min, the water phase was separated and extracted three times with 150-mL portions of ethyl acetate. The water phase was then acidified with concentrated hydrochloric acid (37.0 wt %, 35.5 g, 360.4 mmol, 1.5 eq), the organic phase was separated, and the water phase was again extracted three times with 150-mL portions of ethyl acetate. The combined organic phases were dried over Na₂SO₄ and evaporated to dryness under diminished pressure. The resulting raw product was further purified by distillation in vacuo, yielding the product with a purity of >99% (GC).

The two purified and liquid unsaturated carboxylic acids crystallize spontaneously during storage in a refrigerator at −30 °C as compact polycrystalline materials. Suitable single crystals for X-ray investigations were obtained by slow evaporation of the solvent from ethanolic solutions of each compound at −30 °C over two weeks in small open GC vials.

(E)-hept-2-enoic acid (C7). M. p. −11 °C (lit. –12 °C–−11 °C) [42]; ¹H NMR (400 MHz, CDCl₃): δ = 12.20 (br s, 1H, OH); 7.08 (dt, ³J = 15.6 Hz, ³J = 7.0 Hz, 1H, –CH–); 5.82 (dt, ³J = 15.6 Hz, ⁴J = 1.6 Hz, 1H, –CH–); 2.26–2.20 (m, 2H, –CH₂–); 1.49–1.41 (m, 2H, –CH₂–); 1.39–1.30 (m, 2H, –CH₂–); 0.91 (t, ³J = 7.2 Hz; 3H, –CH₃–). ¹³C NMR (100 MHz, CDCl₃): δ = 172.59 (CO); 152.61 (CH); 120.79 (CH); 32.12 (CH₂); 30.09 (CH₂); 22.33 (CH₂); 13.90 (CH₃). MS (EI, 70eV): m/z = 128 (M⁺, 3), 110 (10), 99 (37), 87 (11), 86 (18), 82 (12), 81 (14), 73 (68), 71 (11), 69 (14), 68 (47), 67 (15), 57 (15), 56 (46), 55 (41), 54 (14), 53 (33), 52 (11), 51 (22) 50 (14), 45 (51), 43 (58), 42 (23), 41 (100), 40 (19), 39 (98), 38 (21), 29 (51). HRMS (ESI-TOF/MS): calculated for C₇H₁₂O₂ ([M − H]⁻) 127.07645, found 127.07660. Elemental analysis for C₇H₁₂O₂% (calc.): C 65.58 (65.60); H 9.58 (9.44).

(E)-oct-2-enoic acid (C8): M. p. 10 °C (lit. 2 °C–6 °C) [43,44]; ¹H NMR (400 MHz, CDCl₃): δ = 11.83 (br s, 1H, OH); 7.09 (dt, ³J = 15.6 Hz, ³J = 7.0 Hz, 1H, –CH–); 5.82 (dt, ³J = 15.6 Hz, ⁴J = 1.6 Hz, 1H, –CH–); 2.25–2.19 (m, 2H, –CH₂–); 1.51–1.43 (m, 2H, –CH₂–); 1.34–1.27 (m, 4H, 2x –CH₂–); 0.91–0.86 (m, 3H, –CH₃–). ¹³C NMR (100 MHz, CDCl₃): δ = 172.56 (CO); 152.66 (CH); 120.78 (CH); 32.41 (CH₂); 31.43 (CH₂); 27.68 (CH₂); 22.54 (CH₂); 14.06 (CH₃). MS (EI, 70eV): m/z = 142 (M⁺, 0), 99 (20), 96 (20), 87 (11), 86 (22), 82 (22), 81 (11), 73 (54), 71 (12), 70 (37), 69 (13), 68 (33), 67 (22), 57 (20), 56 (18), 55 (57), 54 (12), 53 (23), 51 (12), 45 (45), 43 (27), 42 (29), 41 (100), 40 (20), 39 (98), 29 (89). HRMS (ESI-TOF/MS): calculated for C₈H₁₄O₂ ([M − H]⁻) 141.0921, found 141.09201. Elemental analysis for C₈H₁₄O₂% (calc.): C 65.50 (65.57); H 9.97 (9.92).

3.4. Crystal Structure Determinations

Data were collected on a Bruker Kappa APEX II Duo diffractometer [45]. The structures were solved by direct methods (SHELXS-97) and refined by full-matrix least-squares procedures (SHELXL-2014) on F² with the SHELXTL software package [46,47]. Data were corrected for absorption effects using the multi-scan method (SADABS) [48]. All non-hydrogen atoms were refined anisotropically. For C7, H1 could be found from the difference Fourier map and was refined freely. For C8 the carboxyl group is affected by disorder, which is apparent in equal C–O bond lengths. This could not be further resolved reasonably by applying a splitting model and geometric restraints. H1 and H2A are found from the difference Fourier map and were refined with U_iso(H) fixed at 1.5 U_eq(O) and site occupancy factors of 0.5. All other H atoms were placed in idealized positions with d(C–H) = 0.95 Å (CH), 0.99 Å (CH₂), 0.98 Å (CH₃) and refined using a riding model with U_iso(H) fixed at 1.2 U_eq(C) for CH and CH₂ and 1.5 U_eq(C) for CH₃. Crystal data, data collection, and refinement parameters are collected in Table 1. The DIAMOND program package was used for graphical representations [49]. Crystallographic data for the structural analyses have been deposited with the Cambridge Crystallographic Data Centre—CCDC-1475066 for (E)-hept-2-enoic acid (C7), and CCDC-1475065 for (E)-oct-2-enoic acid (C8). These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44 1223 336033; E-mail: [email protected].

4. Conclusions

The crystal and molecular structures of ((E))-hept-2-enoic acid (C7) and ((E))-oct-2-enoic acid (C8) exhibiting the lowest melting points for odd- and even-numbered homologues within the series of α,β-unsaturated carboxylic acids are reported. By analogy to other known crystal structures of this class of substances, C7 and C8 are characterized by carboxylic acid dimers linked by pairs of O–H∙∙∙O hydrogen bonds.