Substitution means the replacement of a hazardous material or process with an alternative which reduces or eliminates the hazard. Process engineers/designers, operations managers, and plant technical staff should continually ask if less hazardous alternatives can be effectively substituted for all hazardous materials used in a manufacturing process. Examples of substitution in two categories are discussed

  • reaction chemistry
  • solvent usage

There are many other areas where opportunities for substitution of less hazardous materials can be found, for example, materials of construction, heat transfer media, insulation, and shipping containers.

Reaction Chemistry

Basic process chemistry using less hazardous materials and chemical reactions offers the greatest potential for improving inherent safety in the chemical industry. Alternate chemistry may use less hazardous raw material or intermediates, reduced inventories of hazardous materials, or less severe processing conditions. Identification of catalysts to enhance reaction selectivity or to allow desired reactions to be carried out at a lower temperature or pressure is often a key to development of inherently safer chemical synthesis routes. Some specific examples of innovations in process chemistry which result in inherently safer processes include:

  • The insecticide carbaryl can be produced by several routes, some of which do not use methyl isocyanate, or which generate only small quantities of this toxic material as an in-process intermediate
  • Acrylonitrile can be manufactured by reacting acetylene with hydrogen cyanide:

CH=CH + HCN -----> CH2=CHCN

A new ammoxidation process uses less hazardous raw materials (propylene and ammonia).

CH2=CHCH3 + NH3 + 3/2(O2) -----> CH2=CHCN + 3H2O

This process does produce HCN as a by-product in small quantities.

  • The Reppe process for manufacture of acrylic esters uses acetylene and carbon monoxide, with a nickel carbonyl catalyst having high acute and longterm toxicity, to react with an alcohol to make the corresponding acrylic ester:

CH=CH + CO + ROH -----> CH2=CHCO2R

The new propylene oxidation process uses less hazardous materials to manufacture acrylic acid, followed by esterification with the appropriate alcohol:

CH2=CHCH3 + 3/2(O2) -----> CH2=CHCO2H + H2O

CH2=CHCO2H + ROH -----> CH2=CHCO2R + H2O

  • Polymer supported reagents, catalysts, protecting groups, and mediators can be used in place of the corresponding small molecule materials. The reactive species is tightly bound to a macromolecular support which immobilizes it. This generally makes toxic, noxious, or corrosive materials much safer. The use of polystyrene sulfonic acid catalyst for the manufacture of methyl t-butyl ether (MTBE) from methanol and isobutene (isobutylene) is one example in commercial use.

CH3OH + CH2=C(CH3)2 -----> CH3=OC(CH3)3

  • The chemistry of side reactions and by-products may also offer opportunities for increasing the inherent safety of a process. For example, a process involving a caustic hydrolysis step uses ethylene dichloride (EDC; 1,2-dichloroethane) as a solvent. Under the reaction conditions a side reaction between sodium hydroxide and EDC produces small but hazardous quantities of vinyl chloride:

C2H4Cl2 + NaOH -----> C2H3Cl + NaCl + H2O

  • Phase transfer catalysis processes for the synthesis of many organic materials use less, or sometimes no, organic solvent; may use less toxic solvent; may allow use of less hazardous raw materials (for example, aqueous HCI instead of anhydrous HCI); and may operate at milder conditions. Some types of reactions where phase transfer catalysis has been applied include:
    1. esterification
    2. nucleophilic aromatic substitution
    3. dehydrohalogenation
    4. oxidations
    5. alkylation
    6. aldol condensations

Innovative chemical synthesis procedures have been proposed as offering potential for economical and environmentally friendly routes to a variety of chemicals. These novel chemical reactions also offer potential for increasing the inherent safety of processes by eliminating hazardous materials, eliminating chemical intermediates, or allowing less severe operating conditions. Some examples of interesting and potentially inherently safer chemistries include:

  • Electrochemical techniques, proposed for the synthesis of naphthaquinone, anisaldehyde, and benzaldehyde
  • Extremozymes - enzymes that can tolerate relatively harsh conditions, suggested as catalysts for complex organic synthesis of fine chemicals and pharmaceuticals
  • Domino reactions, in which a series of carefully planned reactions occurs in a single vessel, used to prepare complex biologically active organic compounds
  • Solid superacid catalysts, proposed as replacements for catalysts such as hydrogen fluoride and aluminum chloride for processes such as alkylation and acylation
  • Laser light "micromanaged” reactions, directed to the production of desired products
  • Supercritical processing, allowing the use of less hazardous solvents such as carbon dioxide or water in chemical reactions. This benefit must be balanced against the high temperatures and pressures required for handling supercritical fluids


Replacement of volatile organic solvents with aqueous systems or less hazardous organic materials improves safety of many processing operations and final products. In evaluating the hazards of a solvent, or any other process chemical, it is essential to consider the properties of the material at the processing conditions. For example, a combustible solvent is a major fire hazard if handled above its flash point or boiling point.

Some examples of solvent substitutions include:

  • Water based paints and adhesives, replacing solvent based products
  • Less volatile solvents with a higher flash point, used for agricultural formulations. In many cases, aqueous or dry flow-able formulations for agricultural chemicals may be used instead of organic formulations
  • Aqueous and semi-aqueous cleaning systems, used for printed circuit boards and other industrial degreasing operations
  • Abrasive media cleaning systems, replacing hazardous organic solvents for paint stripping
  • N-Methyl pyrrolidone, dibasic ethers, and organic esters, substituting for more hazardous paint removers

There has been an active effort to substitute inherently safer and more environmentally friendly solvents in many industries. There are scores of solvent substitutions which have been made in a variety of industries, including food processing, textile, wood and furniture, printing, and casting. The United States Environmental Protection Agency has been developing an expert system to aid in solvent substitution for the printing industry.