Preparation of 2-ethylhexanol

Background and overview[1-3]
2-Ethylhexanol is an important pharmaceutical intermediate, which has important applications in the fields of medicine and chemical industry. It has been reported in the literature that it can be used to prepare isononanoic acid and fatty amines.
Preparation[1]
1. Synthesis of 2-ethyl-2-enehexanal
In a 250 mL three-necked flask, add butyraldehyde (30 g, 0.42 mol), 5% aqueous sodium hydroxide solution (15 mL) and ethanol (50 mL), stir in a water bath at 40°C overnight, check the reaction by TLC, remove the ethanol by rotary evaporation, and use 100 mL of ethyl acetate. The ester was extracted three times, the organic layers were combined, washed with pure water, washed with brine, dried over anhydrous magnesium sulfate, filtered and spin-dried to obtain a light yellow transparent liquid (13.8 g, yield 52%).
2. Synthesis of 2-ethyl-2-enhexanol
Into a 100mL three-necked flask was added 2-ethyl-2-enehexanal (5g, 40 mmol), sodium borohydride (3g, 80 mmol), anhydrous methanol (20mL), and the reaction was stirred at room temperature for 3h, and added under ice bath conditions. Purified water 10mL, extracted with ethyl acetate, combined the organic layers, washed with purified water, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, spin-dried, purified by column chromatography to obtain 4.36g of colorless transparent liquid, yield: 85 %. 1H NMR (500 MHz, CDCl3): 5.39 (t, J=7.5 Hz, 1H), 4.05 (d, J=1 Hz, 2H), 2.15–2.10 (q, J=8 Hz, 2H), 2.06–2.02 (q,J=7.5 Hz,2H), 1.76(s,1H), 1.44–1.36(m,2H), 1.01(t,J=7.5 Hz,3H), 0.93(t,J=7.5 Hz,3H) , 13C NMR (500 MHz, CDCl3): 140.7, 126.2, 66.8, 29.4, 22.9, 21.0, 13.9, 13.2.
3. Synthesis of (S)-2-ethylhexanol
Under a nitrogen atmosphere, the bisphosphorus ligand ChenPhos (3.28 mg, 0.0021 mmol), Rh(NBD) 2BF4, (1.50 mg, 0.002 mmol) and dichloromethane (2 mL) were added to a 10 mL reaction inner tube, and the mixture was stirred for 30 minutes. minutes, a yellow clear liquid is obtained, which is the catalyst.
Add 2-ethyl-2-enhexanol (25.6mg, 0.2 mmol), then place the inner tube in the hydrogenation reactor, change the system into hydrogen atmosphere through three hydrogenation and degassing operations, and finally pressurize to 50 atm, stirred at room temperature for 20 hours. The reaction was stopped, gas was released, the reaction system was concentrated by rotary evaporation, and filtered through a silica gel column to obtain a colorless oily liquid (25.2 mg), the yield was 97%, 98.3% ee. [α]D15+3.9 (c 1.0, chloroform), 1H NMR (500 MHz, CDCl3): 3.54 (d, J=5 Hz, 2H), 1.46–1.28 (m, 8H), 0.94–0.85 (m, 8H) ).
Determination of ee value: GC analysis conditions: Chiral beta-dex-120 column (30m×0.25 mm ID×0.25μm), t nitrogen carrier gas flow rate: 105.6 mL/min, column temperature 110 °C, tS=25.61 min (S) and tR=25.11 min(R).
Application[2-3]
Application 1.
Isononanoic acid is a mixture of structurally branched C9 monocarboxylic acids and is an important intermediate product in industrial organic chemistry that can be processed to generate many transformation products for various applications. For example, its salts are used as drying accelerators or driers for coatings.
CN201380031857.3 reports a method for the production of isononanoic acid carboxylate from 2-ethylhexanol, which starts from 2-ethylhexanol and produces octene by dehydrating 2-ethylhexanol , and then hydroformylation to produce isononanoic aldehyde, which is then oxidized to produce isononanoic acid, and isononanoic acid carboxylate is produced by esterification of the thus produced isononanoic acid with alcohol, and is involved in its use as a lubricant or thermoplastic. Use of plasticizers.
Application 2.
Fatty amines are important organic intermediates for industrial large-scale production. For example, the further processing of fatty amines to produce medicinal products, agrochemicals or dyes, or their use as additives in surfactant formulations, as corrosion inhibitors and as additives in lubricants, for example in their two In the form of thiocarbamates or the corresponding salts, they are used to improve the abrasion resistance of machinery operating under high pressure, or as auxiliaries for the paper, textile and rubber industries. Short chain amines having less than 6 carbon atoms per alkyl group and fatty amines having about 8 to 24 carbon atoms per alkyl group are of particular industrial importance.
CN201380034507.2 reported isononylamine prepared from 2-ethylhexanol, and relates to its preparation method. The method generates octene by dehydration of 2-ethylhexanol, and then hydroformylates to form isononanal, optionally Subsequent hydrogenation to isononyl alcohol followed by reductive amination or alternatively ammonolysis to isononylamine, and its use as corrosion inhibitor, as auxiliary in rubber formulations, as vulcanization accelerator and as additive in lubricants Use to improve the wear resistance of machinery operating under boost pressure. #pharmaceutical intermediates#
  references
[1] [China Invention, China Invention Authorization] CN201310240627. Synthesis method of X(R)- or (S)-2-ethylhexanol
[2] [China Invention, China Invention Authorization] CN201380031857.3 Method for preparing isononanoate from 2-ethylhexanol
[3] [China Invention, China Invention Authorization] CN201380034507.2 Isononylamine prepared from 2-ethylhexanol, its preparation method and its use