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

The molecular structures of the two lowest melting oddand 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 P1 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) Å3 (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) Å3 (T = 200(2) K).


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.

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.  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. 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.

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.

General Considerations
NMR spectra were recorded on a AV300 or AV400 spectrometer (Bruker, Billerica, MA, USA) and chemical shifts of the 1 H, and 13 C spectra were reported in parts per million (ppm) using the solvent shifts for 1 H and 13 C as internal standard (CDCl3: 1 H δ = 7.26, 13 C δ = 77.0). Elemental analysis  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.

General Considerations
NMR spectra were recorded on a AV300 or AV400 spectrometer (Bruker, Billerica, MA, USA) and chemical shifts of the 1 H, and 13 C spectra were reported in parts per million (ppm) using the solvent shifts for 1 H and 13 C as internal standard (CDCl3: 1 H δ = 7.26, 13 C δ = 77.0). Elemental analysis 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.

General Considerations
NMR spectra were recorded on a AV300 or AV400 spectrometer (Bruker, Billerica, MA, USA) and chemical shifts of the 1 H, and 13 C spectra were reported in parts per million (ppm) using the solvent shifts for 1 H and 13 C as internal standard (CDCl 3 : 1 H δ = 7.26, 13 C 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, N 2 atmosphere, Al crucible). All melting points are peak temperatures.

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%).

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 Na 2 SO 4 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.

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 F 2 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 (CH 2 ), 0.98 Å (CH 3 ) and refined using a riding model with U iso (H) fixed at 1.2 U eq (C) for CH and CH 2 and 1.5 U eq (C) for CH 3 . 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: deposit@ccdc.cam.ac.uk.

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.