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Tuesday, 02 August 2011 23:58

Aldehydes and Ketals

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Aldehydes are members of a class of organic chemical compounds represented by the general structural formula R–CHO. R may be hydrogen or a hydrocarbon radical—substituted or unsubstituted. The important reactions of aldehydes include oxidation (whereby carboxylic acids are formed), reduction (with the formation of alcohol), aldol condensation (when two molecules of an aldehyde react in the presence of a catalyst to produce a hydroxy aldehyde), and the Cannizzaro reaction (with the formation of an alcohol and the sodium salt of an acid). Ketals, or acetals, as they are also called, are diesters of aldehyde or ketone hydrates. They are produced by reactions of aldehydes with alcohols.


Because of their high chemical reactivity, aldehydes are important intermediates for the manufacture of resins, plasticizers, solvents and dyes. They are used in the textile, food, rubber, plastics, leather, chemical and health care industries. The aromatic aldehydes and the higher aliphatic aldehydes are used in the manufacture of perfumes and essences.

Acetaldehyde is primarily used to manufacture acetic acid, but it is also used in the manufacture of ethyl acetate, peracetic acid, pyridine derivatives, perfumes, dyes, plastics and synthetic rubber. Acetaldehyde is utilized for silvering mirrors, hardening gelatin fibers, and as an alcohol denaturant and a synthetic flavoring agent. Paraldehyde, a trimer of acetaldehyde, is used in the dyestuff and leather industries and as a hypnotic agent in medicine. Industrially it has been used as a solvent, rubber activator and antioxidant. Metaldehyde is used as a fuel in portable cooking stoves and for slug control in gardening. Glycidaldehyde has been used as a cross-linking agent for wool finishing, for oil tanning, and for fat liquoring of leather and surgical sutures. Propionaldehyde is utilized in the manufacture of polyvinyl and other plastics and in the synthesis of rubber chemicals. It also functions as a disinfectant and as a preservative. Acrolein is used as a starting material for the manufacture of many organic compounds, including plastics, perfumes, acrylates, textile finishes, synthetic fibres and pharmaceuticals. It has been used in military poison gas mixtures and as a liquid fuel, an aquatic herbicide and biocide, and a tissue-fixative in histology.

Formaldehyde has an extremely wide range of uses related to both its solvent and germicidal properties. It is used in plastics production (e.g., urea-formaldehyde, phenol-form-aldehyde, melamine-formaldehyde resins). It is also used in the photography industry, in dyeing, in the rubber, artificial silk and explosives industries, tanning, precious metal recovery and in sewage treatment. Formaldehyde is a powerful antiseptic, germicide, fungicide and preservative used to disinfect inanimate objects, improve fastness of dyes on fabrics, and preserve and coat rubber latex. It is also a chemical intermediate, an embalming agent and a fixative of histological specimens. Paraformaldehyde is the most common commercial polymer obtained from formaldehyde and consists of a mixture of products with different degrees of polymerization. It is used in fungicides, disinfectants, bactericides and in the manufacture of adhesives.

Butyraldehyde is used in organic synthesis, mainly in the manufacture of rubber accelerators, and as a synthetic flavoring agent in foods. Isobutyraldehyde is an intermediate for rubber antioxidants and accelerators. It is used in the synthesis of amino acids and in the manufacture of perfumes, flavorings, plasticizers and gasoline additives. Crotonaldehyde is used in the manufacture of n-butyl alcohol and crotonic acid and in the preparation of surface active agents, pesticides and chemotherapeutic agents. It is a solvent for polyvinyl chloride and acts as a shortstopper in vinyl chloride polymerization. Crotonaldehyde is used in the preparation of rubber accelerators, the purification of lubricating oils, leather tanning, and as a warning agent for fuel gases and for locating breaks and leaks in pipes.

Glutaraldehhyde is an important sterilizing agent effective against all microorganisms, including viruses and spores. It is used as a chemical disinfectant for cold sterilization of equipment and instruments in the health care industry and as a tanning agent in the leather industry. It is also a component of embalming fluid and a tissue fixative. p-Dioxane is a solvent in pulping of wood and as a wetting and dispersing agent in textile processing, dye-baths, stain and printing compositions. It is used in cleaning and detergent preparations, adhesives, cosmetics, fumigants, lacquers, paints, varnishes, and paint and varnish removers.

Ketals are used in industry as solvents, plasticizers, and intermediates. They are capable of hardening natural adhesives like glue or casein. Methylal is used in ointments, perfumes, special purpose fuel, and as a solvent for adhesives and coatings. Dichloroethyl formal is used as a solvent and as an intermediate for polysulphide synthetic rubber.

Safety Precautions

Many aldehydes are volatile, flammable liquids which, at normal room temperatures, form vapours in explosive concentrations. Fire and explosion precautions, as described elsewhere in this chapter, must be most rigorous in the case of the lower members of the aldehyde family, and safeguards with respect to irritant properties must also be most extensive for the lower members and for those with an unsaturated or substituted chain.

Contact with aldehydes should be minimized by attention to plant design and handling procedure. Spillages should be avoided where possible and, where they occur, adequate water and drainage facilities should be available. For those chemicals labelled as known or suspected carcinogens, routine precautions for carcinogens, described elsewhere in this chapter, must be applied. Many of these chemicals are potent eye irritants and approved chemical eye and face protection should be mandatory in the plant area. For maintenance work, plastic face shields should also be worn. Where conditions require, suitable protective clothing, aprons, hand protection and impervious foot protection should be provided. Water showers and eye irrigation systems should be available in the plant area and, as with all protective equipment, operators must be fully trained in their use and maintenance.

Health Hazards

Most of the aldehydes and ketals are capable of causing primary irritation of the skin, eyes and respiratory system—a tendency which is most pronounced in the lower members of a series, in members that are unsaturated in the aliphatic chain, and in the halogen-substituted members. The aldehydes can have an anaesthetic effect, but the irritant properties of some of them may force a worker to limit exposure prior to having sufficient exposure to suffer anaesthetic effects. The irritating effect on the mucous membranes may be related to the ciliostatic effect where the hairlike cilia that line the respiratory tract and provide essential clearance functions are disabled. The degree of toxicity varies greatly in this family. Some of the members of the aromatic aldehydes and certain aliphatic aldehydes are rapidly metabolized and are not associated with adverse effects and thus have been found to be safe for use in foods and as flavourings. However, other members of the family are known or suspected carcinogens and due caution must be exercised in all situations in which contact may be possible. Some are chemical mutagens and several are allergens. Other toxic effects include the ability to produce an hypnotic effect. More detailed data on specific family members are included in the text which follows and in the accompanying tables.

Acetaldehyde is a mucous membrane irritant and also has general narcotic action of the central nervous system. Low concentrations cause irritation of the eyes, nose and upper respiratory passages, as well as bronchial catarrh. Extended contact can damage the corneal epithelium. High concentrations cause headache, stupor, bronchitis and pulmonary oedema. Ingestion causes nausea, vomiting, diarrhoea, narcosis and respiratory failure; death may result from damage to kidneys and fatty degeneration of the liver and heart muscle. Acetaldehyde is produced in the blood as a metabolite of ethyl alcohol, and will give rise to facial flushing, palpitations and other disagreeable symptoms. This effect is enhanced by the drug disulphiram (Antabuse), and by exposure to the industrial chemicals cyanamide and dimethylformamide.

In addition to its acute effects, acetaldehyde is a Group 2B carcinogen, that is, it has been classified as possibly carcinogenic to humans and a carcinogen in animals by the International Agency for Research on Cancer (IARC). Acetaldehyde induces chromosomal aberrations and sister-chromatid exchange in a variety of test systems.

Repeated exposure to the vapours of acetaldehyde causes dermatitis and conjunctivitis. In chronic intoxication, the symptoms resemble those of chronic alcoholism, such as loss of weight, anaemia, delirium, hallucinations of sight and hearing, loss of intelligence and psychic disturbances.

Acrolein is a common atmospheric pollutant which is produced in the exhaust fumes of internal combustion engines, which contain many and varied aldehydes. Acrolein concentration is increased when diesel oil or fuel oil is used. In addition acrolein is found in tobacco smoke in considerable quantities, not only in the particulate phase of the smoke, but also, and even more, in the gaseous phase. Accompanied by other aldehydes (acetaldehyde, propionaldehyde, formaldehyde, etc.) it reaches such a concentration (50 to 150 ppm) that it seems to be among the most dangerous aldehydes in tobacco smoke. Thus acrolein represents a possible occupational and environmental hazard.

Acrolein is toxic and very irritating, and its high vapour pressure may result in the rapid formation of hazardous atmospheric concentrations. Vapours are capable of causing injury to the respiratory tract, and the eyes can be injured by both liquid and vapours. Skin contact may produce severe burns. Acrolein has excellent warning properties and severe irritation occurs at concentrations less than those expected to be acutely hazardous (its powerful lacrimatory effect in very low concentrations in the atmosphere (1 mg/m3) compels people to run away from the polluted place in search of protective devices). Consequently, exposure is most likely to result from leakage or spillage from pipes or vessels. Serious chronic effects, such as cancer, however, may not be completely avoided.

Inhalation presents the most serious hazard. It causes irritation of nose and throat, tightness of the chest and shortness of breath, nausea and vomiting. The bronchopulmonary effect is very severe; even if the victim recovers from acute exposure, there will be permanent radiological and functional damage. Animal experiments indicate that acrolein has a vesicant action, destroying respiratory tract mucous membranes to such an extent that respiratory function is fully inhibited within 2 to 8 days. Repeated skin contact may cause dermatitis, and skin sensitization has been observed.

The discovery of the mutagenic properties of acrolein is not recent. Rapaport pointed it out as long ago as 1948 in Drosophila. Research has been carried out to establish whether cancer of the lung, whose connection with the abuse of tobacco is unquestionable, can be traced to the presence of acrolein in the smoke, and whether certain forms of cancer of the digestive system that are found to have a link with the absorption of burnt cooking oil are due to the acrolein contained in the burnt oil. Recent studies have shown that acrolein is mutagenic for certain cells (Drosophila, Salmonella, algae such as Dunaliella bioculata) but not for others (yeasts such as Saccharomices cerevisiae). Where acrolein is mutagenic for a cell, ultrastructural changes can be identified in the nucleus which are reminiscent of those caused by x rays in algae. It also produces various effects on the synthesis of DNA by acting on certain enzymes.

Acrolein is very effective in inhibiting the activity of the cilia of the bronchial cells that help to keep the bronchial tree clear. This, added to its action favouring inflammation, implies a good probability that acrolein can cause chronic bronchial lesions.

Chloroacetaldehyde has very irritant properties not only with regard to mucous membranes (it is dangerous to the eyes even in the vapour phase and can cause irreversible damage), but also to the skin. It can cause burnlike injuries on contact at 40% solution, and an appreciable irritation at 0.1% solution on prolonged or repeated contact. Prevention should be based on the avoidance of any contact and the control of atmospheric concentration.

Chloral hydrate is mainly excreted in humans first as trichloroethanol and then, as time progresses, as trichloroacetic acid, which may reach up to half the dose in repeated exposure. On severe acute exposure chloral hydrate acts like a narcotic and impairs the respiratory centre.

Crotonaldehyde is a strongly irritant substance and a definite corneal burn hazard, resembling acrolein in toxicity. Some instances of sensitization in workers have been reported and some assays for mutagenicity have produced positive results.

In addition to the fact that p-dioxane is a dangerous fire hazard, it has also been classified by IARC as a Group 2B carcinogen, that is, an established animal carcinogen and possible human carcinogen. Inhalation studies in animals have demonstrated that p-dioxane vapour can cause narcosis, lung, liver and kidney damage, irritation of the mucous membrane, congestion and oedema of the lungs, behavioural changes and elevated blood counts. Large doses of p-dioxane administered in drinking water have led to the development of tumours in rats and guinea pigs. Animal experiments have also demonstrated that dioxane is rapidly absorbed through the skin producing signs of incoordination, narcosis, erythema as well as liver and kidney injury.

Experimental studies with humans have also shown eye, nose, and throat irritation at concentrations of 200 to 300 ppm. An odour threshold as low as 3 ppm has been reported, although another study resulted in an odour threshold of 170 ppm. Both animal and human studies have demonstrated that dioxane is metabolized to β-hydroxyethoxyacetic acid. An investigation in 1934 of the deaths of five men working in an artificial silk plant suggested that the signs and symptoms of dioxane poisoning included nausea and vomiting followed by diminished and finally absence of urine output. Necropsy findings included enlarged pale livers, swollen haemorrhagic kidneys and oedematous lungs and brains.

It should be noted that unlike many of the other aldehydes, the irritant warning properties of p-dioxane are considered poor.

Formaldehyde and its polymeric derivative paraformaldehyde. Formaldehyde polymerizes readily in both liquid and solid state to form the mixture of chemicals known as paraformaldehyde. This polymerization process is delayed by the presence of water and, consequently, commercial formaldehyde preparations (known as formalin or formol) are aqueous solutions containing 37 to 50% formaldehyde by weight; 10 to 15% methyl alcohol is also added to these aqueous solutions as a polymerization inhibitor. Formaldehyde is toxic by ingestion and inhalation and it may also cause skin lesions. It is metabolized into formic acid. The toxicity of polymerized formaldehyde is potentially similar to that of the monomer since heating produces depolymerization.

Exposure to formaldehyde is associated with both acute and chronic effects. Formaldehyde is a proven animal carcinogen and has been classed as a 1B probable human carcinogen by IARC. Consequently, when working with formaldehyde, appropriate precautions for carcinogens must be taken.

Exposure to low atmospheric concentrations of formaldehyde causes irritation, especially of the eyes and respiratory tract. Due to the solubility of formaldehyde in water, the irritant effect is limited to the initial section of the respiratory tract. A concentration of 2 to 3 ppm causes slight formication of the eyes, nose and pharynx; at 4 to 5 ppm, discomfort rapidly increases; 10 ppm is tolerated with difficulty even briefly; between 10 and 20 ppm, there is severe difficulty in breathing, burning of the eyes, nose and trachea, intense lacrimation and severe cough. Exposure to 50 to 100 ppm produces a feeling of restricted chest, headache, palpitations and, in extreme cases, death due to oedema or spasm of the glottis. Eye burns can also be produced.

Formaldehyde reacts readily with tissue proteins and promotes allergic reactions, including contact dermatitis, which has also arisen from contact with formaldehyde-treated clothing. Asthmatic symptoms may occur due to allergic sensitivity to formaldehyde, even at very low concentrations. Kidney injury may occur in excessive and repeated exposure. There have been reports of both inflammatory and allergic dermatitis, including nail dystrophy due to direct contact with solutions, solids or resins containing free formaldehyde. Inflammation follows even after short-term contact with large quantities of formaldehyde. Once sensitized, the allergic response may follow contact with only very small quantities.

Formaldehyde reacts with hydrogen chloride, and it was reported that such reaction in humid air could yield a non-negligible amount of bis(chloromethyl) ether, BCME, a dangerous carcinogen. Further investigations have shown that at ambient temperature and humidity, even at very high concentrations, formaldehyde and hydrogen chloride do not form bis-(chloromethyl) ether at the detection limit of 0.1 ppb. However, the US National Institute for Occupational Safety and Health (NIOSH) has recommended that formaldehyde be treated as a potential occupational carcinogen because it has shown mutagenic activity in several test systems and has induced nasal cancer in rats and mice, particularly in the presence of hydrochloric acid vapours.

Glutaraldehyde is a relatively weak allergen which can cause allergic contact dermatitis and the combination of irritant and allergen properties are suggestive of the possibility of respiratory system allergies as well. It is a relatively strong irritant to the skin and the eyes.

Glycidaldehyde is a highly reactive chemical which has been classified by IARC as a group 2B possible human carcinogen and established animal carcinogen. Thus precautions appropriate for the handling of carcinogens must be exercised with this chemical.

Metaldehyde, if ingested, may cause nausea, severe vomiting, abdominal pain, muscular rigidity, convulsions, coma and death from respiratory failure. Ingestion of paraldehyde ordinarily induces sleep without depression of respiration, although deaths occasionally occur from respiratory and circulatory failure after high doses or more. Methylal can produce liver and kidney impairment and acts as a lung irritant on acute exposure.

Aldehydes and ketals tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Table 3 - Physical and chemical hazards.

Table 4 - Physical and chemical properties.



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