Study On The Syntheses Of 4-ethyl Octanoic Acid And Its Homologues And On The Application Of 4-ethyl Octanic Acid

Carboxylic acids are important food flavor compounds. Up to now, Flavor and Extract Manufactures Association of the Unite States(FEMA) has published lists, in which including more than 2,600 flavor substances that are"generally recognized as safe"(GRAS), and there are more than 120 carboxylic acids in the list. There are also more than 70 carboxylic acids flavor compounds in the positive lists of food additives in China. According to the characteristics of structure, the carboxylic acids can be divided into saturated carboxylic acids, unsaturated fatty acids, aromatic carboxylic acids, polybasic acid, oxo-carboxylic acid, etc., and the saturated carboxylic acids can be further divided into linear and branched-chain carboxylic acids. The odor of saturated branched-chain carboxylic acids is relevant to not only the length of the carbon chain but the position of the branched-chain. The carboxylic acids with a branched-chain at C4 position have stronger odor. The purposes of the thesis are firstly going on the synthesis of 4-ethyloctanoic acid, the design of synthetic routes of 4-ethyl fatty acid and the preparation of 4-ethyl fatty acid by the designed routes, and the research of the application of 4-ethyloctanoic acid.Rapid synthesis of 4-ethyloctanoic acid under microwave irradiation is described by using diethyl malonate, sodium metal, anhydrous ethanol, 2-ethyl-1-bromide-hexane and potassium hydroxide as main reactants through alkylation reaction, saponification reaction, decarboxylation reaction, etc.. Diethyl malonate reacted with 2-ethyl-1-bromohexane in the presence of sodium ethoxide to give diethyl (2-ethylhexyl)malonate (1b). 1b was saponified in the solution of ethanol and potassium hydroxide and then acidified to form (2-ethylhexyl)propanedioic acid(1c), and 1c was heated and decarboxylized to give 4-ethyloctanoic acid (1d). The structures of intermediates and product were characterized by gas chromatography, infrared spectroscopy, mass spectrometry, high resolution mass spectrometry and nuclear magnetic resonance. Additionally, melting point apparatus was introduced to measure the melting point of 1b. Then reaction temperature, reaction time and the molar ratio of reactants were optimized. In the process of alkylation, the main by-product was isolated and identified, and then its formation mechanism was further discussed. The author found that overdose of sodium metal in the reaction of alkylation would lead to more side products, among which diethyl di(2-ethylhexyl)malonate occupied a large proportion. As the mole ratio of diethyl malonate and 2-ethyl-1-bromide-hexane to sodium increased, the yield of by-product decreased. Furthermore, comparative studies on the effect of heating ways (microwave heating and oil bath) on the yields of products were investigated. After the careful experiments, it can safely draw the conclusion that there do not have significant difference between the two heating methods from the point of view of yields. But at the aspect of reaction time, things become different. Microwave irradiation can, to a large extent, reduce the reaction time, especially the alkylation reaction time. The relative optimal conditions for the synthesis of 1b are a mole ratio of sodium to diethyl malonate to 2-ethylhexyl bromide of 1:1.1:1.1, a reaction temperature of 80–85°C, and a reaction time of 2–2.5 h. The yield of 1b is about 79%. 1b is saponified for 30 min and then acidified to form 1c, and the yield of 1c is about 96%. 1c is heated for 16 min at 180°C to give 1d, and the yield of 1d is about 92%. The overall yield of 1d is about 70% under microwave irradiation. For the sake of evaluating the aroma of 4-ethyloctanoic acid, it is diluted to a 1% of the propylene glycol solution. The evaluation result shows that it has waxy,fatty, milky flavor with a slight animal-like odor.By using magnesium, 1-bromoethane, aldehydes, thionyl chloride, methyl 3-bromopropionate, potassium hydroxide, concentrated hydrochloric acid as raw material, 20 compounds had been synthesized through series of reactions, such as Grignard reaction, nucleophilic addition reaction, substitution reaction, coupling reaction, saponification and acidification reactions. They are 3-alkanols (C₅-C₉), 3-chloroalkanes (C₅-C₉), 4-ethyl fatty acid methyl esters (C₉-C₁₃) and 4-ethyl fatty acids (C8-C12). Their structures were identified by gas chromatography, infrared spectroscopy, mass spectrometry, high resolution mass spectrometry and nuclear magnetic resonance. Then, reaction temperature, reaction time, mole ratio of materials and other conditions were optimized to each kind of reaction, respectively. The experiment results show that: 1) The quantity of by-product, 3-alkanone, can be reduced effectively in the preparation of the 3-alkanol, if the dropping rate of aldehyde, reaction temperature and reaction time were well controlled with nitrogen atmosphere; 2) 3-Chloroalkanes with high content can be synthesized by the reaction of thionyl chloride with 3-alkanol under the optimal conditions, which were a mole ratio of thionyl chloride to 3-alkanol of 2.4:1, a mole ratio of pyridine to 3-alkanol of 1:1, and a reaction time of 2-3h. 3) When 3-bromoheptane reacts with methyl 3-bromopropionate to prepare methyl 4-ethyloctanoate, the yield is low. At the same time, the reaction need carry out at lower temperature and form more by-products. On the contrary, when 3-chloroheptane reacts with methyl 3-bromopropionate to prepare methyl 4-ethyloctanoate, the yield is much higher than the former. The reaction temperature is about -10℃, and fewer by-products are produced. The relative optimal conditions for the synthesis of methyl 4-ethyloctanoate were a mole ratio of 3-chloroheptane to methyl 3-bromopropionate of 2:1, a reaction temperature of -10℃, a reaction time of 3h and 4% amount of catalyst (based on total molar quantity of methyl 3-bromopropionate). The yield of the methyl 4-ethyl octanoate is about 67%. This optimal condition can be applied to synthesize other 4-ethyl fatty acid methyl ester. Under the same reaction condition, the preparations of other four esters are conducted to get methyl 4-ethylhexanoate, methyl 4-ethylheptanoate, methyl 4-ethylnonaoate and methyl 4-decanoate, whose yields are 70%, 68%, 72% and 77%, respectively. 4) Five 4-ethyl fatty acid methyl esters in solution of methanol and potassium hydroxide are refluxed for 3h at 70℃to give the corresponding salt, and the molar ratio of potassium hydroxide to esters is 2.8:1. Acidification of the reaction mixture with HCl liberated the free 4-ethylfatty acid. The yields of 4-ethylhexanoic acid, 4-ethylheptanoic acid, 4-ethyloctanoic acid, 4-ethylnonaoic acid and 4-ethyl decanoic acid are 95%, 97%, 98%, 96% and 92%, respectively. Finally, the odor characteristics of five 4-ethyl fatty acids were evaluated. The results show that they have different flavor characteristics, and 4-ethyl-heptanoic acid and 4-ethyloctanoic acid have better odors.Because of the higher reaction activity of 4-ethyloctanoyl chloride, 4-ethyloctanoic acid was converted into 4-ethyloctanoyl chloride. 4-ethyloctanoyl chloride reacted with 3-(methylthio)propanol, 2-metyl-3- tetrahydrofuranthiol, 4-methyl-5-thiazoleethanol, 2-methyl-3-furanthiol, furfuryl mercaptan, benzyl alcohol, phenethanol, 3-phenyl-1-propanol and cinnamyl alcohol to produce their corresponding esters, respectively. These esters were synthesized in the laboratory for the first time. The structures of 4-ethyloctanoyl chloride and nine new esters were characterized by gas chromatography, infrared spectroscopy, mass spectrometry, high resolution mass spectrometry and nuclear magnetic resonance. Then, the reaction conditions were optimized. The experiment results show that: 1) the mole ratio of materials have more effect on yield, and the 9 new esters have been obtained in higher yields (about 90%) under the optimal reaction condition. 2) In the study of all the esterification reactions, as the mole ratio of alcohol to 4-ethyloctanoyl chloride increased, only the yields of 4-methyl-5-thiazoleethanol 4-ethyloctanoate decreased. This phenomenon is related to the characteristics of the starting materials. In the reaction producing 4-methyl-5-thiazoleethanol 4-ethyloctanoate, the 4-methyl-5- thiazoleethanol used as a starting material has multiple nucleophilic centers (O, S and N), which may react with 4-ethyloctanoyl chloride to give the product or byproducts. Although the reaction temperature and steric-hindrance effect are not appropriate to form byproducts, the yield of byproduct increased as the ratio of 4-methyl-5-thiazoleethanol to 4-ethyloctanoyl chloride increased. 3) All nine ester flavor compounds have relatively high molecular weights (> 260) and are therefore less volatile, which can prolong the flavoring lifetime to improve the flavoring quality. Finally, the five new sulfur-containing esters were evaluated by GC-Olfactometry, and the four aromatic esters were evaluated by placing a drop of the material on a clean strip of odorless absorbent paper specially manufactured for this purpose and smelling this material at certain intervals. The odor evaluation results indicate that the sulfur-containing esters have meaty odor, and the aromatic eaters have sweet and floral odor.In order to investigate the use of 4-ethyloctanoic acid in mutton flavoring, braised lamb in brown sauce flavoring and fried lamb with cumin flavoring were formulated. The results show 4-ethyloctanoic acid can impart the characteristic odor of mutton to the flavorings.