Allylamine hydrochloride: properties and applications of stable organic amine derivatives

Allylamine Hydrochloride, also known as allylamine hydrochloride and 3-aminopropylene hydrochloride, is a protonated salt compound formed by the reaction of allylamine and hydrochloric acid. The molecular formula is C₃H₈ClN, and the simplified structural formula is CH₂=CH-CH₂-NH₃Cl. CAS No. 10017-11-5, molar mass 93.56 g·mol⁻¹. As an important derivative of allyl ammonia, it significantly improves chemical stability through protonation of the amino group, reduces volatility and irritation, and retains the reactivity of the allyl double bond. It has become a key intermediate that is easier to store and control in the fields of medicine, organic synthesis, polymer materials, etc., effectively making up for the shortcomings of free allyl ammonia that are lively and difficult to control.
1. Core chemical properties: performance optimization after protonation modification

The performance advantage of allyl ammonium hydrochloride comes from the protonation reaction of amino groups and hydrochloric acid to form a stable ammonium salt structure, which not only retains the reactivity of the allyl group, but also improves the physical and chemical defects of the free amine, making it suitable for a wider range of industrial and laboratory scenarios.

In terms of physical properties, allylamine hydrochloride is a white crystalline powder with no obvious odor. Compared with free allylamine (a colorless and irritating liquid), its stability is greatly improved. Its melting point is 140-143°C. It is easy to decompose when heated above the melting point. The decomposition products may be allyl ammonia, hydrochloric acid and a small amount of polymer, so it needs to be stored at low temperature. This compound is easily soluble in polar solvents such as water, methanol, ethanol, and slightly soluble in non-polar solvents such as acetone and ether. The aqueous solution is weakly acidic (pH value is about 3-4, 1% aqueous solution), and its solubility in water can reach more than 300 g/L (25°C). It is accompanied by a slight exotherm during dissolution. The purity of industrial-grade products is usually ≥98%, and the purity of high-end pharmaceutical grade can reach more than 99.5%. The impurities are mainly trace amounts of moisture, free hydrochloric acid and diallylamine hydrochloride. Through precise purification, the metal ion content can be controlled to ≤1 ppm, meeting the needs of the electronics and pharmaceutical fields.

Chemically, its core properties are determined cooperatively by the protonated amino group (-NH₃⁺) and the allyl double bond. First, the stability of the ammonium salt: Compared with the strong reducibility and easy oxidation of free allyl ammonia, the hydrochloride is not easily oxidized at normal temperatures and pressures, nor is it prone to self-polymerization, and the storage period can reach more than 12 months (sealed and dry conditions); The second is the reactivity of the double bond: it retains the addition, polymerization and cycloaddition capabilities of the allyl double bond, and can react with halogens and hydrogen halides , acrylates, etc., and the reaction selectivity is better than that of free amines, and the alkalinity of the amino group is not likely to interfere with the reaction process; the third is the characteristic reaction of ammonium salts: it can react with alkali (such as sodium hydroxide, sodium carbonate) to deprotonate, regenerate free allyl ammonia, and provide the possibility of controlled release; at the same time, it can react with reagents such as silver nitrate to generate silver chloride precipitation, which can be used for qualitative detection. In addition, this compound is prone to double bond polymerization under high temperature or strongly alkaline conditions, and the reaction environment parameters need to be strictly controlled.

2. Preparation process: based on protonation and purification of allylamine

The preparation of allylamine hydrochloride uses high-purity allylamine as the core raw material. Through precise control of the protonation reaction and purification process, the purity and yield of the product are optimized. Industrial production has formed a mature large-scale process, and laboratory preparation focuses on simplicity and accuracy.

(1) Industrial scale preparation process

Industrial preparation uses "allylamine protonation-crystallization purification-drying packaging" as the core process. The key is to control the reaction pH and temperature to avoid side reactions. The first step, raw material pretreatment: purify industrial grade allylamine (purity ≥98%) through distillation to remove by-products such as diallylamine and triallylamine to ensure that the purity of the raw material meets the needs of subsequent reactions; the second step, protonation reaction : In a low-temperature reaction kettle (0-10°C), slowly drop dilute hydrochloric acid (concentration 20%-30%) into allyl ammonia, control the molar ratio of allyl ammonia to hydrochloric acid to 1:1.05-1.1, and stir the rate 50-80 r/min, monitor the pH value of the reaction system in real time until the pH is stable at 3-4, stop dripping; the third step, crystallization and purification: heat the reaction solution to 40-50°C, concentrate under reduced pressure until a large number of crystals appear, then slowly cool down to 0-5°C, and let stand at constant temperature for 2- For 4 hours, the crystals are fully separated, and the crude product is obtained by centrifugation; the fourth step is refining and drying: the crude product is recrystallized with absolute ethanol 1-2 times to remove traces of free amines and salt impurities, and then dried in a vacuum drying oven (60-70°C, vacuum degree -0.09~-0.1 MPa) dry for 4-6 hours, control the moisture content ≤0.5%, and finally obtain the finished product. The yield of this process can reach more than 92%, and the by-product is only a small amount of wastewater, which can reach the standard discharge after neutralization treatment. The environmental protection is better than the preparation process of free allyl ammonia.

(2) Laboratory preparation methods

Laboratory preparation focuses on simplicity of operation and product purity, and is suitable for small-batch synthesis. Take 100 mL of purified allylamine and place it in a three-neck flask, add a condenser tube and a constant pressure dropping funnel, place it in an ice water bath and cool it to 0°C; slowly add 120 mL concentration of 25% hydrochloric acid, the dripping rate is controlled at 1-2 drops/second, stir continuously during the dripping process to avoid local overheating and double bond polymerization; after the dripping is completed, continue stirring for 30 minutes, raise the temperature to 50°C and concentrate under reduced pressure until it becomes viscous, add 50 Dissolve mL of absolute ethanol and filter to remove insoluble impurities; place the filtrate in a refrigerator (0°C) overnight to precipitate white crystals. After filtering, wash twice with a small amount of ice-cold ethanol and dry in a vacuum drying oven at 60°C for 2 hours. Allylamine hydrochloride with a purity of ≥99% can be obtained to meet experimental needs.

(3) Purification process optimization direction

In response to the demand for high-purity products in the high-end field, the purification process can be further optimized: the "recrystallization + molecular sieve adsorption" combination technology is used to remove trace amounts of moisture and organic impurities, raising the purity to more than 99.8%; for electronic-grade products, an additional membrane separation process can be added to reduce the content of metal ions (Fe, Cu, Pb, etc.) to less than 0.1 ppm; by controlling the crystallization rate (cooling rate 0.5°C/h), crystals with uniform particles can be obtained, improving product fluidity and storage stability.

3. Application areas: Stable intermediates empower multi-industry upgrades

Allylamine hydrochloride has the advantages of high stability and strong reaction controllability. Its application scenarios cover the fields of medicine, organic synthesis, polymer materials, analysis and testing, etc. It is especially suitable for scenarios with high requirements on raw material stability and safety. The global annual consumption is about 12,000 tons, and it continues to grow with the development of high-end pharmaceutical and functional materials industries.

(1) Pharmaceutical and pesticide fields: high-purity intermediate core raw materials

The pharmaceutical field is the core application scenario of allylamine hydrochloride, accounting for more than 45% of total consumption. It is mainly used to synthesize active intermediates such as antifungal drugs, antiviral drugs, and antitumor drugs. For example, using it as raw material, allyl imidazole, an imidazole antifungal intermediate, can be prepared through condensation and cyclization reactions. This intermediate can be further modified to obtain commonly used clinical drugs such as clotrimazole and miconazole. Compared with using free allyl amino, the hydrochloride can significantly improve the reaction selectivity, reduce the formation of by-products, and improve product purity. In the synthesis of antiviral drugs, it can be used to prepare reverse transcriptase inhibitor intermediates, and active groups are introduced through double-bond addition reactions to enhance the targeting of drugs to viruses. In addition, it can also be used to synthesize antihistamines, anesthesia auxiliary drugs, etc. Its high stability can avoid the degradation of drug intermediates during the synthesis process and ensure drug efficacy.

In the field of pesticides, it is used to prepare high-efficiency and low-toxic fungicides and insecticide intermediates, such as the precursor synthesis of allylamine fungicides propiconazole. The hydrochloride form can simplify the reaction process, reduce irritation and danger during the production process, and at the same time increase product yield. The heterocyclic compounds derived from it have a significant inhibitory effect on plant fungal diseases (such as rice sheath blight and wheat powdery mildew), and have good environmental degradability, which is in line with the development trend of green pesticides.

(2) Field of organic synthesis: functional intermediates with controllable reactions

As a stable amino donor in organic synthesis, allylamine hydrochloride can be used to prepare various fine chemicals. At the same time, it serves as an amino protection form to simplify the synthesis path of complex molecules. In heterocyclic synthesis, heterocyclic compounds such as pyrrole, piperidine, and quinoline can be prepared by reacting with diketones, carboxylic esters, etc. These heterocyclic rings are the core skeletons of dyes, spices, and fluorescent materials; in amine derivatization reactions, free allylamine can be regenerated through deprotonation. It participates in acylation and alkylation reactions as needed to avoid volatilization losses and safety risks when free amines are used directly. In addition, it can also be used to prepare compounds such as allyl urea and allyl isocyanate, which are widely used in the fields of polyurethane cross-linking agents and antibacterial agent synthesis.

(3) Field of polymer materials: functionally modified precision monomers

The double bonds of allylamine hydrochloride can participate in homopolymerization or copolymerization reactions. The protonated amino group gives the polymer cationic properties and water solubility, making it an important monomer for functional modification of polymer materials. The first is to prepare a cationic polymer: it homopolymerizes itself to form polyallylamine hydrochloride. This polymer has good water solubility, flocculation and antibacterial properties. It can be used as a flocculant in water treatment to effectively remove anionic pollutants and suspended particles in the water. particles and bacteria, the dosage is only 1/3-1/2 of traditional flocculants, and there is no secondary pollution; the second is copolymerization modification: copolymerization with acrylonitrile, acrylic acid, acrylamide and other monomers can improve the hydrophilicity, adhesion and biocompatibility of the polymer Capacitive, used to prepare water-based coatings, medical polymer materials (such as antibacterial dressings), papermaking retention aids, etc. For example, polymers copolymerized with acrylamide can significantly improve the strength and water resistance of paper; third, surface modifiers: used for surface treatment of substrates such as metals and fibers. A modified layer is formed through double-bond polymerization. The protonated amino group can enhance the interfacial bonding force between the substrate and the resin while imparting antibacterial properties. It is suitable for use in medical fibers, food packaging materials and other scenarios.

(4) Other featured applications

In the field of analysis and detection, it can be used as a standard reagent for the qualitative and quantitative analysis of amine compounds. By reacting with alkali to release allyl ammonia, combined with gas chromatography detection, it can accurately determine the content of free amines in the sample; in the field of catalysis, it can be used as a ligand with metal ions (such as Pd²⁺, Ni²⁺ ) to form a complex catalyst for olefin polymerization and hydrogenation reactions to improve catalytic activity and selectivity; in addition, it can also be used to prepare corrosion inhibitors. In industrial circulating water systems, it forms a protective film on the metal surface by adsorption to inhibit metal corrosion, and its stability is better than that of free allyl ammonia corrosion inhibitors.

4. Safety, environmental protection and industry development trends

(1) Safety control and environmental protection requirements

Allylamine hydrochloride is significantly less dangerous than free allylamine, has no strong irritating odor, is not volatile, and is not a flammable or explosive hazardous chemical, but safety control is still required. It is slightly corrosive. Contact with skin and eyes may cause redness, swelling and stinging. Inhalation of dust may irritate the respiratory mucosa. Wear dust masks, acid and alkali resistant gloves, and protective glasses during operation. Keep the operating environment well ventilated; store in a cool, dry place. In a sealed container, keep away from fire sources, oxidants, and strong alkalis, avoid moisture and high temperatures, and prevent crystals from agglomerating or decomposing. If leakage occurs, sand or dry lime must be used to adsorb and collect the wastewater. The wastewater should be neutralized (pH adjusted to 6-8) before being discharged to avoid contaminating water bodies.

In terms of environmental protection, a small amount of wastewater generated during industrial production mainly contains trace amounts of hydrochloric acid and ammonium salts. After deamination and biochemical treatment, it can be discharged to the standard. The ammonia recovered from deamination can be recycled for the preparation of allyl ammonia to realize resource recycling; the crystallization mother liquor can recover ethanol through distillation to reduce raw material loss; the solid waste is mainly a small amount of impurity filter residue, which can be disposed of as general industrial solid waste after harmless treatment. The overall environmental protection pressure is much lower than that of free allyl ammonia production.

(2) Industry development trends

The allyl ammonia hydrochloride industry is evolving towards high-end, refinement and greening, forming a coordinated development pattern with allyl ammonia. At the technical level, the research and development of high-end pharmaceutical grade and electronic grade products has become the core competitiveness. Through upgrading the purification process, the impurity content is further reduced to meet the stringent needs of biomedicine, electronic materials and other fields; in terms of green production, the reaction process is optimized to achieve an increase in raw material utilization rate to over 95%. , to promote the construction of full mother liquor recovery and zero-emission system, and reduce environmental protection costs; at the application level, with the development of new energy and medical polymer materials industries, its applications in cationic flocculants, antibacterial medical materials, high-end catalytic ligands and other fields will be further expanded, and the added value of derivative products continues to increase.

In terms of market structure, global production capacity is currently mainly concentrated in China, Europe and the United States. Domestic companies have achieved independent mass production of industrial-grade products through technological breakthroughs. Some companies have deployed pharmaceutical-grade high-purity products to gradually replace imports. In the future, with the growth of demand in downstream high-end fields, the market share of high-purity allylamine hydrochloride will continue to expand. At the same time, the synergy with the allylamine industry chain will be further highlighted, promoting the industrial upgrading of the entire allylamine series products.

As a stable derivative of allylamine, allylamine hydrochloride effectively expands the application boundaries of allylamine compounds with its controllable reactivity, excellent stability and low safety risks. Driven by technological innovation and green manufacturing, it will play a more important role in the fields of medicine, high-end materials, environmental protection and other fields, becoming a key intermediate connecting basic organic synthesis and high-end industries.