Basic introduction Chinese name: aldol condensation mbth: aldol reaction alias: condensation reaction application discipline: organic chemistry application scope: chemical reaction catalyst: acid/base catalyst, etc. Brief introduction, reaction process, reaction mechanism, reaction catalyst, application in organic chemistry, other reactions, introducing aldehyde with α-H, generating carbanion under the catalysis of dilute alkali, then generating β-hydroxyaldehyde as nucleophilic reagent for nucleophilic addition of aldehydes and ketones, and heating and dewatering to generate unsaturated aldehyde. Aldehyde condensation Under the action of dilute alkali or dilute acid, two molecules of aldehyde or ketone can interact, in which the α-hydrogen in one molecule of aldehyde (or ketone) is added to the carbonyl oxygen atom of the other molecule, and the rest is added to the carbonyl carbon atom, resulting in a molecule of β-hydroxyaldehyde or a molecule of β-hydroxyketone. This reaction is called aldol condensation or aldol condensation. Through aldol condensation, new carbon-carbon bonds can be formed in molecules and carbon chains can grow. The reaction process takes acetaldehyde as an example to illustrate the condensation reaction process of aldol. In the first step, alkali combines with α -hydrogen in acetaldehyde to form enol negative ions or negative carbon ions. In the second step, this negative ion, as a nucleophile, immediately attacks the carbonyl carbon atom in another acetaldehyde molecule to generate an intermediate negative ion (alkoxy negative ion) after the addition reaction. Thirdly, alkoxy anions react with water to obtain hydroxyaldehyde and OH. Dilute acid can also change aldehyde into hydroxyaldehyde, but the reaction process is different. In the process of acid catalysis, firstly, the polarization of carbon-oxygen double bond is enhanced by protons, making it into enol form, and then an addition reaction takes place to obtain hydroxyaldehyde. The α-hydrogen atom in the product molecule is activated by carbonyl and hydroxyl groups on β-carbon at the same time, so only a small amount of heat or acid is needed to dehydrate the molecule to produce α, β-unsaturated aldehyde. All β -hydroxyaldehydes and ketones with hydrogen atoms on α -carbon are easy to lose a water molecule. This is because α-hydrogen is more active, and the dehydrated product has * * * yoke double bonds, so it is more stable. Except acetaldehyde, aldol condensation products obtained from other aldehydes are all aldol or alkenal with branched chain on α-carbon atom. Aldehyde condensation reaction plays an important role in organic synthesis, which can be used to grow carbon chains and produce branched chains. Reaction mechanism Aldehyde condensation is nucleophilic addition of carbon anion to carbonyl carbon. The carbonyl structure in aldehyde or ketone molecule makes the hydrogen atom on α carbon atom have great activity. Under the action of acid catalyst, carbonyl oxygen atom is protonated, which enhances the induction of carbonyl group and promotes the dissociation of α hydrogen to produce enol. The reaction mechanism of acid catalysis: under the action of alkaline catalyst, α carbon atom loses hydrogen atom to form carboanion * * * vibration hybrid, and after reaching equilibrium, enol salt is generated. Mechanism of base-catalyzed reaction: Enol salt then undergoes nucleophilic addition with carbonyl group of another aldehyde or ketone, forming a new carbon-carbon single bond to obtain β -hydroxy aldehyde or ketone. Because the α-hydrogen atom is relatively active, β-hydroxyaldehyde or ketone containing α-hydrogen atom is easy to lose one molecule of water and form more stable α, β-unsaturated aldehyde or ketone with yoke double bond structure. Acid-catalyzed dehydration mechanism: alkali-catalyzed dehydration mechanism: two different aldehydes or ketones cross-condense with the reaction catalyst, and the selectivity is low due to many side reactions in the non-catalytic process. It is necessary to make the selectivity of target products meet the requirements of industrial application through catalytic process. The catalysts used in the reaction can be divided into acid catalysts, alkaline catalysts and acid-base catalysts according to their acid-base active centers. 1 Acid Catalysts Commonly used acid catalysts are (VO)2P207, niobic acid and MFI zeolite. At the cationic active center (Brnsted center or Lewis center) of acidic catalyst, aldehyde carbonyl group is activated to form enol carbonium ion, which leads to condensation reaction. The balance of acid-catalyzed enolketone can be expressed by the existing research results. The type, quantity and distribution of acid active centers on the surface of the catalyst will affect its catalytic performance. Proper acid strength can effectively promote the formation of carbon ions in the gas-phase aldol condensation reaction and improve the reaction activity. Tanner et al. used vanadium phosphate oxides of (VO)2P2P7 and α VOHPO4 as catalysts to study the self-condensation of acetone and the cross-condensation of acetone with formaldehyde. The results show that the acidic active center of vanadium phosphate catalyst has good catalytic ability for this reaction, and the carbonyl structural group quickly completes the protonation and nucleophilic addition reaction on its surface. Paulis et al. used niobic acid (Nb2o5 nH2O) as catalyst to carry out vapor-phase aldol condensation reaction of acetone, and found that the types of reaction products were closely related to the acid strength and acidity of the acid center of the catalyst. The results show that the acidic central acid on the surface of niobic acid catalyst is strong, and it has good catalytic activity, selectivity and stability in acetal and ketal reactions. Dumitriu et al. used MFI zeolites with different acidity in the gas-phase aldol condensation reaction of low-carbon aldehydes. The acid strength and acidity of Bronsted acid center can be adjusted by changing the ratio of Si to Fe3+ in the catalyst. It is found that the enhancement of surface acid strength can promote the gas-phase aldol condensation reaction of low-carbon aldehydes and improve the conversion rate. 2. Basic Catalysts Basic catalysts commonly used in aldol condensation reactions include basic compounds (oxides, hydroxides, bicarbonates, carbonates and carboxylates of alkali metals or alkaline earth metals), organic amines and anion exchange resins. In practical industrial applications, the basic catalysts used for aldol condensation reaction can be weak bases (such as sodium carbonate, sodium bicarbonate and sodium acetate) or strong bases (such as sodium hydroxide, calcium hydroxide, sodium hydride and sodium alkoxide). The former is generally used for condensation between highly active aldehydes, and the products are mostly β -hydroxy compounds; The latter is used for the condensation reaction of aldehydes or ketones with small activity and large steric hindrance, and the reaction is mostly carried out in aprotic polar solvents. Alkali metal compound catalysts are often used in the reaction of aldol condensation to prepare aldol. The obtained product can be hydrogenated and purified to obtain diol or even polyol, such as 3- hydroxybutyraldehyde obtained by self-condensation of acetaldehyde. When caustic soda solution is used as catalyst, 1, 3- butanediol can be obtained by catalytic hydrogenation of crude product. Similarly, formaldehyde and butyraldehyde cross-condense to form 2,2-dimethylol butyraldehyde. Choosing the mixed solution of sodium carbonate and sodium hydroxide as catalyst can reduce side reactions and improve reaction selectivity. Lopez et al. used NaBEA, KF/ alumina and La2O3 solid catalysts respectively to study the deactivation mechanism of catalysts in aldol condensation reaction of benzaldehyde and acetophenone. The results show that benzoic acid produced in the reaction process will greatly reduce the transfer rate of proton hydrogen in the reaction process, but the addition of amine has little effect on the rate, so it is considered that the basic active center of the catalyst can effectively catalyze the reaction, and the deactivation of the catalyst is also related to the loss of the basic active center. Organic amine is another basic catalyst widely used in aldol condensation reaction. For example, triethylamine is often used as condensation catalyst in the condensation reaction of formaldehyde and isobutyraldehyde to generate hydroxyl neopentyl glycol, and the condensation product is hydrogenated to obtain neopentyl glycol. Formaldehyde and n-butyraldehyde are condensed and then hydrogenated under the catalysis of triethylamine to produce high-purity hydroxymethylpropane. This patent reports an organic amine salt condensation catalyst, which is used in the process of preparing 1, 3- propanediol by aldol condensation. Anion exchange resin is a new alkaline catalyst. Traditional alkali metal hydroxide solutions (such as nAOH and KOH) as catalysts have some disadvantages, such as difficult catalyst recovery, easy corrosion of equipment, complicated reaction process and long production cycle. However, anion exchange resin overcomes the above shortcomings on the basis of maintaining catalytic activity, which has attracted more and more researchers' attention. The industrial production of 2,2-dimethylolpropionic acid mainly takes formaldehyde and propionaldehyde as raw materials, and generates 2,2-dimethylolpropionic acid through aldol condensation reaction under the catalysis of inorganic or organic bases, and then oxidizes it with hydrogen peroxide. The latest research shows that the reaction effect depends on the specific surface area of spherical catalyst, the number of active groups, the speed of adsorption and desorption, etc. The catalyst exists in solid form, which avoids a series of problems of using lye as catalyst and ensures the conversion rate and selectivity of the reaction.
In the industrial synthesis of 2- methyl -2- pentenal, NaOH aqueous solution is also widely used as a catalyst, and the yield is about 80%. However, NaOH aqueous solution will corrode the experimental equipment, and the product is not easy to separate. Tang Siping studied the new process of preparing 2- methyl -2- pentenal by bimolecular condensation of propionaldehyde with anion exchange resin as catalyst. The yield of the target product 2- methyl -2- pentenal can reach 93.54%. There are also many reports about the application of anion exchange resin in aldol condensation reaction in China. Ou Zhize and others chose tributylamine aminated strongly basic anion exchange resin as phase transfer catalyst to catalyze the synthesis of benzylidene acetone. Under the optimized reaction conditions, the yield of benzylidene acetone can reach 98%, and the catalyst can be reused. Hu Wei et al. chose strongly basic styrene quaternary ammonium ion exchange resin as catalyst to prepare acetoethanol by condensation of acetone and formaldehyde, and then dehydrated in the presence of oxalic acid to obtain methyl ketene. Shi Xiumin and others developed and screened a new type of anionic catalyst, macroporous strongly basic styrene anionic resin, which is suitable for catalytic distillation of diacetone alcohol, and has high catalytic activity and selectivity. Aldehyde condensation reaction in organic chemistry is an important organic chemical reaction, which is widely used in organic synthesis. Aldehyde condensation reaction refers to the reaction that compounds containing active α hydrogen atoms, such as aldehydes, ketones, carboxylic acids, esters, etc., undergo nucleophilic addition reaction with carbonyl compounds under the action of catalysts to obtain α-hydroxy aldosterone or acid, or further dehydrate to obtain α, β-unsaturated aldosterone or ester. ① Intermolecular aldol condensation is often used to synthesize some β -hydroxy compounds, such as 1, 3- propanediol, 1, 3- butanediol, neopentyl glycol, etc. It can be used as a monomer for further producing polymers such as perfume and medicine or polymers such as polyethylene terephthalate (PET), polybutylene terephthalate (PBT) and polypropylene terephthalate (PTT). The α, β-unsaturated aldehyde, a product of condensation and dehydration, is oxidized to obtain the corresponding carboxylic acid, which can be widely used as raw materials for fine chemical production. For example, 2,2-dimethylolpropionic acid can be used as water-based polyurethane chain extender and to prepare polyester, photosensitive resin and liquid crystal. 2- methyl -2- pentenoic acid is a kind of edible spice with fruit flavor, which can be widely used in food processing industry and other daily chemical essence industries. In addition, when α, β-unsaturated aldehydes are completely hydrogenated, saturated primary aldehydes can be obtained, which can be used as solvents or in the manufacture of detergents and plasticizers. Although other ketones containing α-hydrogen can also undergo this kind of condensation reaction under the action of dilute alkali, it is difficult to carry out the reaction due to the influence of electronic effect and spatial effect. If you operate in the ordinary way, basically you can't get the product. Generally speaking, the reaction needs to be carried out under special conditions. For example, acetone can be converted into diacetone alcohol in the presence of alkali, but the yield in equilibrium system is very low. If the product can be separated from the alkali catalyst immediately after production, it can be separated from the equilibrium system, and finally more acetone can be converted into diacetone alcohol, and the yield can reach 70% ~ 80%. Catalyzed by iodine, diacetone alcohol can be dehydrated by heating to produce α, β-unsaturated ketone. Cross aldol condensation: The condensation reaction between different aldehyde and ketone molecules is called cross aldol condensation. If all aldehydes and ketones have α-hydrogen atoms, four kinds of products can be generated after the reaction, and the actual mixture is always complicated and has no practical value. Some aldehydes and ketones without α -hydrogen atoms do not undergo aldol condensation reaction (such as HCHO, RCCHO, ArCHO, RCCOCR, ArCOAr, ArCOCR, etc. ), but they can cross aldol condensation reaction with aldehydes and ketones containing α-hydrogen atoms, mainly the reaction between benzaldehyde and formaldehyde. The types of products are reduced, and condensation products are mainly obtained with high yield. In the product after the reaction, the aldehyde group with α -hydrogen atom must be retained. A single product can be obtained by maintaining excess formaldehyde without α -hydrogen atoms during the reaction. Claessen-Schmidt condensation: aldol condensation reaction of aromatic aldehydes with aldehydes and ketones containing α-hydrogen atoms catalyzed by alkali, dehydration to obtain α, β-unsaturated aldehydes and ketones with high yield. This type of reaction is called klassen-Schmidt condensation reaction. Under the catalysis of alkali, benzaldehyde can also be condensed with aliphatic ketones or aromatic ketones containing α -hydrogen atoms. In addition, some compounds containing active methylene, such as malonic acid, dimethyl malonate, ethyl α-nitroacetate, etc., can react with aldehydes and ketones similar to aldol condensation. The main reason is that the strong electron-withdrawing group activates α-H, which is easy to become hydrogen ions and leave. The application of ethyl acetoacetate and diethyl malonate in organic synthesis is also related to it.