1H,1H,7H-Dodecafluoroheptyl Pentafluorobenzoate

Abstract

Polyfluoroarenes are widely used in organic synthesis because they readily undergo nucleophilic substitution reactions. This reactivity prompted us to report the synthesis and spectroscopic characterization of a new compound, 1H,1H,7H-dodecafluoroheptyl pentafluorobenzoate, obtained via three different approaches starting from pentafluorobenzoic acid and 1H,1H,7H-dodecafluoroheptanol.

1. Introduction

Polyfluoroarenes and their derivatives serve as versatile building blocks in organic synthesis. Through organozinc chemistry, for example, these compounds enable access to diverse ketones, which can be further transformed into alcohols [1,2,3], thiazoles [4], functional polymers [5], and other derivatives [6,7,8]. Polyfluoroarenes also readily undergo nucleophilic aromatic substitution with sodium azide to generate aryl azides—key precursors to amines [9,10], amides [11,12,13,14], and N-heterocyclic compounds [15,16]. Additionally, numerous other fluorine substitution reactions are well-documented [1,17,18,19]. Notably, polyfluoroarenes bearing aliphatic chains find application as liquid crystal components [20,21].

In this paper, we report the synthesis and characterization of 1H,1H,7H-dodecafluoroheptyl pentafluorobenzoate (1, Scheme 1), a fluorinated ester with potential utility as a building block for liquid crystals and hydrophobic polymeric materials.

2. Results and Discussion

The target compound 1 was synthesized from commercially available pentafluorobenzoic acid and 1H,1H,7H-dodecafluoro-1-heptanol via three distinct approaches (Scheme 1): (I) acid-catalyzed esterification using concentrated H₂SO₄; (II) acyl chloride alcoholysis; and (III) Steglich-type carbodiimide-mediated coupling.

Scheme 1. Synthetic approaches for synthesis of 1. *—according to GC-MS of reaction mixture.

Scheme 1. Synthetic approaches for synthesis of 1. *—according to GC-MS of reaction mixture.

2.1. Acid-Catalyzed Esterification (Approach I)

We began with a convenient ester synthesis approach, namely esterification in the presence of concentrated sulfuric acid (Approach I, Scheme 1). In this system, 1H,1H,7H-dodecafluoro-1-heptanol and sulfuric acid served as the solvent for pentafluorobenzoic acid.

Initially, the reaction was performed using a 1:1 molar ratio of pentafluorobenzoic acid to alcohol. However, under these conditions, the starting materials were not completely converted to product 1 (after 10 h of heating), as evidenced by the crystallization of pentafluorobenzoic acid during cooling of the reaction mixture. Nevertheless, the target product 1 was obtained in 68% yield after vacuum distillation. To improve the reaction condition and drive the equilibrium toward 1, the alcohol amount was increased to a 2-fold excess. With this modification, the reaction proceeded to full consumption of pentafluorobenzoic acid in 15 h. The isolated yield of 1 was 81%. The increase in the yield is associated with both better conversion of pentafluorobenzoic acid and an increase in the reaction scale, which led to lower losses during distillation.

2.2. Acyl Chloride Alcoholysis (Approach II)

Another method for preparing esters involves the reaction of an alcohol with an acyl chloride (Approach II, Scheme 1). This approach has been used, for example, to synthesize ethyl pentafluorobenzoate without any additives [6,22]. Pentafluorobenzoyl chloride was obtained by reacting pentafluorobenzoic acid with thionyl chloride under heating at 90 °C. However, it was found that 1H,1H,7H-dodecafluoro-1-heptanol, in contrast to ethanol, does not react with pentafluorobenzoyl chloride in the absence of additives. However, the reaction proceeded readily in dichloromethane (DCM) at room temperature upon the addition of triethylamine (1.2 eq.) to the reaction mixture. The isolated yield of 1 was 77%. Notably, most yield loss occurred during the distillation step.

2.3. Steglich-Type Esterification (Approach III)

In Steglich-type esterification, carbodiimides activate carboxylic acids to enable esterification under mild conditions. We performed a Steglich-type esterification using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI) in anhydrous DCM at room temperature. However, after 24 h, the target compound 1 was obtained in a low yield of 32% (determined by GC analysis of the reaction mixture). To improve the yield, we tried to increase the reaction temperature and carried out the reaction under reflux in DCM for 12 h. In this case the yield of 1 was found to be ca. 30% (GC-MS).

3. Materials and Methods

3.1. General Information

¹H and ¹⁹F spectra were recorded on a Bruker Avance 300 (Bruker Corporation, Billerica, MA, USA) instrument (300 MHz ¹H, 282.4 MHz ¹⁹F), and ¹³C NMR spectra were recorded on a Bruker DRX 500 (125.7 MHz) instrument (Bruker Corporation, Billerica, MA, USA). Chemical shifts (δ) are reported in ppm relative to CCl₃F (¹⁹F, upfield negative) and TMS (¹H, ¹³C); C₆F₆ (δF = −162.9 ppm) and CDCl₃ (δC = 76.9 ppm) served as internal standards. Coupling constants (J) are reported in Hz and rounded to the nearest 0.5 Hz. The following abbreviations were used to designate multiplicities: d =doublet, t = triplet, q = quartet, and m = multiplet.

Molecular masses of the compounds were determined by HRMS with a Thermo Electron Corporation DFS (Thermo Fisher Scientific, Waltham, MA, USA) instrument (EI 70 eV).

IR and UV-Vis spectra were recorded on Bruker Vector 22 FT-IR spectrometer (Bruker Corporation, Billerica, MA, USA)and Agilent Cary 5000 spectrophotometer (Agilent Technologies, Santa Clara, CA, USA), respectively.

HPLC analysis was carried out using an HPLC-UV system (Agilent 1100, Agilent Technologies Inc., Santa Clara, CA, USA) including degasser (G1322A), binary pump (G1312A), autosampler (G1329A), thermostated column compartment (G1316A) with a Zorbax RX C18 column (150 × 4.6 mm with 5.0 µm particle size; Agilent Technologies Inc., Santa Clara, CA, USA), diode array detector (DAD G1315B). The column was thermostatically controlled at 30 °C. Gradient elution was used: from 30 to 100%(B) for 18 min, from 100 to 30%(B) for 1 min, 30%(B) for 3 min, where solvent (A) was bidistilled water and solvent (B) was 100% acetonitrile (for HPLC, gradient grade, ≥99.9%; Concord Technology, Tianjin, China). The flow rate was 1.0 mL/min. The sample was dissolved in ACN. The elution volume varied depending on the concentration of prepared solution. Peaks were detected using a maximum wavelength of 210 nm. Peaks from solvents were not included in the purity calculations.

3.2. Synthesis

1H,1H,7H-Dodecafluoroheptyl pentafluorobenzoate (1) (Supplementary Materials)

Approach I.

(a) Pentafluorobenzoic acid (5.30 g, 25 mmol) and 1H,1H,7H-dodecafluoro-1-heptanol (8.30 g, 25 mmol) were charged to a 100 mL flask equipped with a magnetic stir bar. Concentrated H₂SO₄ (2 mL) was added to the mixture with stirring. The reaction mixture was stirred at 120 °C (oil bath temperature) for 10 h. After cooling to room temperature, the mixture was quenched with saturated aqueous NaHCO₃ solution (200 mL). The aqueous phase was extracted with CH₂Cl₂ (2 × 50 mL), and the combined organic extracts were washed with water (2 × 50 mL). The organic phase was dried over MgSO₄, and the solvent was removed by rotary evaporation to afford the crude product as a light-yellow liquid (10.42 g, 79%). Vacuum distillation of the crude material yielded the pure product 1 (8.93 g, 68%) as a colorless liquid (bp 115–120 °C at 3 torr).

(b) Pentafluorobenzoic acid (63.6 g, 300 mmol) and 1H,1H,7H-dodecafluoro-1-heptanol (199.20 g, 600 mmol) were charged to a 250 mL flask equipped with a magnetic stir bar. Concentrated H₂SO₄ (20 mL) was added to the mixture with stirring. The reaction mixture was stirred at 120 °C (oil bath temperature) for 15 h. After cooling to room temperature, the mixture was quenched carefully with saturated aqueous NaHCO₃ solution (300 mL). The aqueous phase was extracted with CH₂Cl₂ (2 × 50 mL), and the combined organic extracts were washed with water (2 × 100 mL). The organic phase was dried over MgSO₄, and the solvent was removed by rotary evaporation to afford the crude product as a light-yellow liquid (215.32 g). Vacuum distillation of the crude material yielded the pure product 1 (128.45 g, 81%) as a colorless liquid (bp 111 °C at 1.8 torr).

UV-Vis (EtOH), λₘₐₓ/nm (lg ε): 216 (3.89), 275 (3.13).

FT-IR (film), ν, cm⁻¹: 3469, 2981, 1759, 1653, 1527, 1506, 1425, 1334, 1202, 1142, 1033, 1002.

¹H NMR (300 MHz, CDCl₃), δ: 4.86 (t, 2H, ³J_HF = 13.2 Hz), 6.05 (tt, 1H, ²J_HF = 52.0 Hz, ³J_HF = 5.1 Hz).

¹³C{¹H} NMR (125.7 MHz, CDCl₃), δ: 158.0 (s, C=O), 146.2 (dm, ¹J_CF = 259.3 Hz), 144.4 (dtt, ¹J_CF = 261.5 Hz, ²J_CF = 13.3 and ³J_CF = 4.9 Hz), 138.1 (dm, ¹J_CF = 256.7 Hz), 114.4 (tt, ¹J_CF = 259.0 Hz, ²J_CF = 30.0 Hz), 113.6–108.2 (m), 107.8 (tt, ¹J_CF = 254.7 Hz, ²J_CF = 31.5 Hz, CF₂H), 106.4 (dt, ²J_CF = 14.6 Hz, J_CF =3.8 Hz), 61.0 (t, ²J_CF = 27.1 Hz, CH₂).

¹⁹F NMR (282.4 MHz, CDCl₃), δ: −120.2 (m, 2F, CF₂), −123.0 (m, 2F, CF₂), −124.2 (m, 4F, CF₂), −137.6 (m, 2F, F-2,6), −138.0 (dm, 2F, CF₂, ²J_FH = 52.0 Hz), −147.1 (tt, 1F, F-4, ³J_FF = 20.9 Hz, ⁴J_FF = 5.9 Hz), −160.7 (m, 2F, F-3,5).

HRMS: found m/z 489.9668 [M]⁺; calculated for C₁₄H₃F₁₇O₂ 489.9669.

Elemental analysis calculated for C₁₄H₃F₁₇O₂ (%): C, 31.96; H, 0.57; F, 61.38; found (%): C, 31.05; H, 0.75; F, 60.99

Approach II. Pentafluorobenzoic acid (5.30 g, 25 mmol) was treated with thionyl chloride (SOCl₂, 4.46 g, 37.5 mmol) and DMF (3 drops) at room temperature. The mixture was heated at 90 °C for 4 h. After cooling to room temperature, excess SOCl₂ was removed by rotary evaporation. To the residue at 0 °C, a solution of 1H,1H,7H-dodecafluoro-1-heptanol (8.30 g, 25 mmol) in CH₂Cl₂ (10 mL) and triethylamine (30 mmol) was added. The reaction mixture was stirred at room temperature for 2 h, then quenched with water (200 mL). The organic phase was separated, and the aqueous phase was extracted with CH₂Cl₂ (2 × 15 mL). The combined organic extracts were washed with water (200 mL) and dried over MgSO₄. After solvent removal by rotary evaporation, crude compound 1 was obtained (12.27 g, 93%). Vacuum distillation yielded 10.14 g (77%) of analytical-grade 1 as a transparent colorless liquid (bp 121–123 °C at 3 mmHg).

Approach III. To a stirred solution of pentafluorobenzoic acid (5.30 g, 25 mmol) in CH₂Cl₂ (75 mL) at room temperature, DMAP (0.15 g, 1.25 mmol) and EDCI (7.19 g, 37.5 mmol) were added. A solution of 1H,1H,7H-dodecafluoro-1-heptanol (8.30 g, 25 mmol) in CH₂Cl₂ (10 mL) was then added, and the reaction mixture was stirred at room temperature for 24 h. Water (200 mL) was added to the mixture, the organic phase was separated, washed with additional water (200 mL), and dried over MgSO₄. According to GC-MS data of reaction mixture, the product 1 yield was 32%.

4. Conclusions

1H,1H,7H-Dodecafluoroheptyl pentafluorobenzoate was synthesized via three chemical approaches. Alcoholysis of pentafluorobenzoyl chloride afforded the target product in a good yield (77%) under relatively mild conditions. Acid-catalyzed esterification using concentrated H₂SO₄ gave the product in considerable yield (81%) with the advantage of a cheaper catalyst, although it required more stringent conditions. Steglich-type esterification employing EDCI was found to be less suitable, as the yield of the target compound was only approximately 30%.