Isovaleraldehyde: Synthesis, application and determination

General description

As an intermediate in the production of fragrances and other organic chemicals, isovaleraldehyde's chemical molecular formula is C5H10O and its molecular weight is 86.13. Isovaleraldehyde naturally exists in essential oils such as citrus and lemon. It has apple-like aroma when highly diluted, and peach aroma when the concentration is lower than 10 ppm. Chinese GB2760-86 stipulates that it is allowed to use as an food flavor, which is mainly used to prepare various fruit essence. This product is the intermediate of the drug antispasmodic agent Xinwokeding.

Figure 1 Appearance of Isovaleraldehyde.

Characteristics

Isovaleraldehyde is a colorless transparent liquid at normal temperature, slightly soluble in water, soluble in ethanol and ether. The melting point, flash point and boiling point are - 51 ℃, 93.5 ℃ and - 5 ℃ respectively. Its density is 0.791 g/cm³ and refractive index is 1.388 (20 ℃).

Chemical synthesis

Isovaleraldehyde can be synthesized by single step according to previous work [1]. A stirred solution of the acetal (3.5 mmol) in dry hexane (5 ml), under dry nitrogen at 25°C, was treated with 1 (1.7 g, 10.6 mmol). The mixture was stirred for 2 h, treated with water, and extracted with dichloromethane (10 ml). The extracts were washed with brine solution, dried (Na₂SO₄), and concentrated in vacuo. The resulting residue was purified by column chromatography on neutral alumina (50-325 mesh, eluent: 2.5:97.5 ethyl acetate-hexane). The corresponding carbonyl compound (3). The purity was estimated to be >98% by ¹H and ¹³C NMR spectroscopic analysis. In the case of solid acetals, 0.5 ml of dichloromethane along with hexane was added for added solubility; in the case of thioacetals, 21.2 mmol of 1 was used for effective deprotection. 3-Methylbutanal (3q). Liquid. υmax 2952, 2937, 2866, 1710, 1468, 1435, 1268, 1158, 1133, 1010, 954, 712; δH 9.756 (1H, s), 2.31-2.30 (2H, m), 2.248-2.170 (1H, m), 0.996-0.979 (6H, d, J 6.7); δC 202.962, 52.547, 23.442, 22.541.

Application

Isovaleraldehyde has many uses in the industial application. It is a multifunctional chemical product, which can prepare a series of products with high added value. As an edible flavor specified in China, it can be used to prepare various fruit essence. In addition, its derivatives such as isovaleric acid, isoamylamine, isovalerate ester compounds can also be used as raw materials for edible essence and daily chemical essence. Isovaleraldehyde is an effective precursor for a large number of chemical products, which can be used for aldol condensation production α，β- Unsaturated aldehydes can also be used to further prepare long-chain alcohols, acids and other important intermediates for plasticizers, detergents and lubricants for further processing. Theobromal can be prepared from isovaleraldehyde through aldol condensation, which is used for essence preparation. It is also an intermediate of diethyl ether electron donor in Ziegler Natta catalyst [2]. Isovaleraldehyde is also an important raw material for many pharmaceutical intermediates, and can be used as a main raw material to produce vitamin E, pregabalin, etc.

Determination

Isovaleraldehyde has no obvious ultraviolet absorption and cannot be directly determined by ultraviolet detector, so it needs to be derivatized. Select 2,4-dinitrophenylhydrazine as the derivatization reagent, phosphoric acid as the acid catalyst, acetonitrile-water (20 ∶ 80, volume ratio) as the solvent, and derivatize for 30 minutes at room temperature. The chromatographic column is C18 (250 mm × 4.6 mm, 5 µ m), acetonitrile (volume fraction of 0.1% formic acid) as mobile phase A, water (volume fraction of 0.1% formic acid) as mobile phase B, and carry out isocratic elution at 80% A for 30 minutes; The flow rate is 1.0 m L · min^-1; The column temperature is 30 ℃; The detection wavelength is 364 nm; The injection volume is 5 µ L. The retention time of isovaleraldehyde was 19.3 min.

[2]Giampietro.Process for the preparation of diethers.EP.487035A2.1991-11-19.

[3]Zhang et al. HPLC determination isovaleraldehyde content in bortezomib. Chinese Journal of Pharmacy. 2020,18(05): 244-249.