In a laboratory setting, acyl chlorides require careful storage and handling due to their reactive nature. They are typically moisture-sensitive and can readily react with water, leading to hydrolysis and degradation. Therefore, acyl chlorides should be stored in airtight containers, preferably under an inert atmosphere like nitrogen or argon, to protect them from moisture in the air. They should be kept in a cool, dry place, away from sources of heat and direct sunlight, which can accelerate decomposition. Additionally, acyl chlorides are often corrosive and can emit fumes that are irritating to the respiratory tract, eyes, and skin. Consequently, they should be handled in a well-ventilated area, such as a fume hood, to avoid inhalation of fumes. Personal protective equipment (PPE), including gloves, safety glasses, and lab coats, should be worn to prevent direct contact with the skin or eyes. The handling of acyl chlorides also requires the use of proper laboratory techniques to prevent exposure and contamination. Glassware and equipment used with acyl chlorides should be thoroughly cleaned and dried to remove any traces of moisture. Any spills or leaks should be dealt with promptly and safely, following appropriate chemical spill protocols.

Acyl chlorides are highly versatile intermediates in organic synthesis and have numerous applications, particularly in the pharmaceutical industry. Due to their high reactivity, they are commonly used in the formation of various other functional groups. For example, acyl chlorides readily react with alcohols to form esters, with amines to form amides, and with water to yield carboxylic acids. These reactions are fundamental in synthesising a wide range of organic compounds, including pharmaceuticals, agrochemicals, and polymers. In pharmaceuticals, acyl chlorides are employed in the synthesis of active pharmaceutical ingredients (APIs). They are used to introduce acyl groups into molecules, which can modify the biological activity of the compound, improve its pharmacokinetic properties, or enhance its stability. Additionally, acyl chlorides are used in peptide synthesis, as they can react with amino acids or peptides to form peptide bonds, a critical step in the production of synthetic peptides and proteins. The ability to selectively react with different nucleophiles also makes acyl chlorides valuable in the synthesis of complex molecules, where controlling the reactivity and selectivity is crucial. Furthermore, their use in the synthesis of dyestuffs, fragrances, and other fine chemicals highlights their broad applicability in various sectors of the chemical industry.

The use of phosphorus pentachloride (PCl₅) in the synthesis of acyl chlorides poses several environmental and safety concerns. Firstly, PCl₅ is highly reactive and can be hazardous if not handled correctly. It reacts violently with water to produce hydrochloric acid and heat, which can lead to dangerous situations in the presence of moisture. This necessitates strict anhydrous conditions and careful handling to avoid accidental exposure to water. Additionally, the reaction of PCl₅ with carboxylic acids produces not only the desired acyl chloride but also phosphoryl chloride (POCl₃) and hydrogen chloride (HCl), both of which are harmful. POCl₃ is toxic and can pose health hazards if inhaled or if it comes into contact with the skin. Hydrogen chloride, on the other hand, is corrosive and can lead to respiratory issues if inhaled. The disposal of these by-products must be managed carefully to minimise environmental impact. The handling and disposal of PCl₅ and its by-products require adherence to strict environmental regulations and safety protocols to prevent contamination and protect both human health and the environment. Proper ventilation, use of personal protective equipment (PPE), and containment measures are essential when working with PCl₅.

Thionyl chloride (SOCl₂) is frequently preferred over phosphorus trichloride (PCl₃) and phosphorus pentachloride (PCl₅) for converting carboxylic acids to acyl chlorides due to several advantages. Firstly, the reaction with SOCl₂ usually proceeds at a lower temperature and under milder conditions compared to PCl₃ and PCl₅. This reduces the risk of unwanted side reactions and makes it safer to handle. Secondly, the by-products of the reaction with SOCl₂ are sulfur dioxide (SO₂) and hydrogen chloride (HCl), both of which are gases at room temperature. This makes the separation of the acyl chloride product from the reaction mixture much simpler and more efficient, as the gaseous by-products can be easily removed by venting. Additionally, SOCl₂ is a more selective reagent. It does not generally react with other functional groups present in the molecule, which is particularly advantageous when dealing with complex molecules. This selectivity allows for greater control over the reaction and minimises the production of undesired side products. Moreover, SOCl₂ can often react directly with the carboxylic acid without the need for an additional solvent, making the process more convenient and environmentally friendly.

Acyl chlorides are significantly more reactive than other acid derivatives such as esters or amides. This increased reactivity is primarily due to the presence of the chlorine atom, which is a very good leaving group. In acyl chlorides, the carbon-chlorine bond is polarised, with the chlorine atom being more electronegative. This polarization makes the carbonyl carbon more susceptible to nucleophilic attack. In contrast, esters and amides have less polarisable oxygen and nitrogen atoms, respectively, as the adjacent atom to the carbonyl carbon. These atoms are less electronegative compared to chlorine, making esters and amides less reactive towards nucleophiles. Amides, in particular, are the least reactive among common acyl derivatives due to the presence of a nitrogen atom that can donate electron density to the carbonyl group, thereby reducing its electrophilicity. The high reactivity of acyl chlorides makes them excellent intermediates in organic synthesis, as they can readily react with a wide range of nucleophiles to form various other functional groups, such as esters, amides, and carboxylic acids, under relatively mild conditions.