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The following four hypothetical scenarios demonstrate how to use the tools described in this Guide to Developing Standard Operating Procedures. The entries in the four forms were completed by the expert committee and are solely for illustrative purposes; real situations will call for procedures that are suited to the specific laboratory surroundings and personnel.

SCENARIO 1: NEUTRALIZATION OF CARBONATE BY ACID

Overview: This scenario describes a situation in which a student with moderate experience is conducting a routine procedure of neutralizing a carbonate species with acid in a chemical laboratory at a university.

SCENARIO:

The student wants to hydrolyze an ester. The chemical reaction is carried out in an aqueous-organic medium with sodium carbonate or bicarbonate as the base. The desired product is soluble in the excess aqueous base. To obtain the product, the medium is neutralized with concentrated hydrochloric acid. The use of concentrated acid helps keep the total reaction fluid volume low, thereby optimizing precipitation or extraction of the product. The vigorous effervescent release of carbon dioxide, however, is a potential concern to the student. How should the student proceed?

Suggested solution:

Moderate Risk Standard Operating Procedure Form

1. TITLE AND DESCRIPTION OF EXPERIMENT OR PROCESS: Hypothetical workup of a reaction medium requiring neutralization of carbonates using concentrated hydrochloric acid

2. PREPARER(S): [name]

3. LOCATION: Laboratory

4. AUTHORIZED PERSONNEL (WITH CONTACT INFORMATION)

a. PRINCIPAL INVESTIGATOR (PI)/SUPERVISOR: [name] (555) 343-1515

b. STUDENT(S)/TECHNICIAN(S)/OPERATOR(S): [name] (555) 321-5762

c. OTHERS TO BE NOTIFIED (e.g., other workers in the same laboratory, or other members of the research group): [name] (555) 724-8921

5. POTENTIAL HAZARDS: Concentrated hydrochloric acid (HCl, 37%). Hydrochloric acid is corrosive and causes burns on eyes, skin, and digestive and respiratory tracts. It may be fatal if inhaled or swallowed. Repeated exposure may cause erosion of exposed teeth.

6. DESCRIBE ALL SPECIAL REQUIREMENTS FOR SPECIFIC ITEMS THAT REQUIRE A GREATER LEVEL OF SAFETY

7. IDENTIFY ANY TRAINING NEEDS No specific training required

9. VERIFICATION AND REVIEW

By signing below, you acknowledge that you have read, understand, and approve the SOP.

9. LIST OF REFERENCES (include Safety Data Sheets, Globally Harmonized System, any outside personnel consulted in the preparation of the document, peer reviewers, etc.)

Moderate Risk Standard Operating Procedure Review and Modifications Log

Were modifications made to current SOP?	Yes No
If no, then list date of approval
Last reviewed by (please print)
If yes, then list and describe modifications

Were modifications made to current SOP?	Yes No
If no, then list date of approval
Last reviewed by (please print)
If yes, then list and describe modifications

Were modifications made to current SOP?	Yes No
If no, then list date of approval
Last reviewed by (please print)
If yes, then list and describe modifications

SCENARIO 2: USE AND FILTRATION OF A PYROPHORIC CATALYST

Overview: This scenario describes a situation where an inexperienced researcher wants to complete a reaction using a pyrophoric heterogeneous catalyst, followed by a filtration workup step.

SCENARIO:

A newly hired researcher in an industrial laboratory is using a pyrophoric heterogeneous catalyst in a hydrogenation reaction. After reviewing section 9.7.4 of the National Academies of Sciences, Engineering, and Medicine report, A Guide to Prudent Chemical Management, the researcher discovers special hazards that may be encountered when filtering the hydrogen-saturated catalyst from the flammable organic reactants.

Suggested solution:

To minimize fires and explosions during the filtration step, the researcher goes through a hazard assessment checklist. After completing the assessment checklist, the researcher concludes that he/she will need a High Risk SOP.

High Risk Standard Operating Procedure Form

1. TITLE AND DESCRIPTION OF EXPERIMENT OR PROCESS: Pyrophoric/ignitable catalyst: Procedure for addition to reaction vessel and separation from reaction mixture by filtration

2. PREPARER(S): [name]

3. LOCATION: industrial laboratory

4. AUTHORIZED PERSONNEL (WITH CONTACT INFORMATION)

a. PRINCIPAL INVESTIGATOR (PI)/SUPERVISOR: [name] (555) 123-4567

b. STUDENT(S)/TECHNICIAN(S)/OPERATOR(S): [name] (555) 401-6333

c. OTHERS TO BE NOTIFIED (e.g., other workers in the same laboratory, or other members of the research group): [name] (555) 202-3333

5. IDENTIFY ANY TRAINING NEEDS

6. DETAILED PROCESS DESCRIPTION

This SOP covers the use of a wide variety of pyrophoric catalysts. The catalysts may become pyrophoric after exposure to reducing agents (e.g., organic solvents, hydrogen) or are pyrophoric as obtained from vendors.

It is essential that the activated catalyst does not become dry or exposed to air, especially in the presence of solvent vapors, or a fire will result. Raney metal catalysts are pyrophoric as obtained from vendors and are typically provided as water slurries to prevent ignition. These catalysts must be wetted during all manipulations.

The fire potential is mitigated by (1) keeping the pyrophoric catalyst wetted with solvent and/or water during all stages of handling, including final transfer to a waste container, (2) maintaining an inert gas purge or blanket above the pyrophoric catalyst, and (3) eliminating clutter and any additional fuel sources from the immediate work area.

DETAILED PROCEDURE:

Column A: Process Steps provide detailed step-by-step normal operating procedures, including the transfer of chemicals between or across laboratories, production of gases, workup of products, and preparation of wastes.

Column B: Safety Notes describe how the risk can be mitigated (i.e., minimize clutter, control flammables, secure gas cylinders, ensure good condition of pump belts).

7. ENGINEERING CONTROLS (check all that apply and provide a detailed description)

Engineering Controls	Check box if applicable	Description
Ex. Glove box		Use inert air (N2 or Ar)
Fume hood or glove box
Special ventilation
HEPA-filtered vacuum lines
Non-reactive containers
Pressure relief devices
Temperature control
Bench paper, pads, plastic-backed paper
Special signage
Safe sharp devices
Other safety devices used:

8. PERSONAL PROTECTIVE EQUIPMENT (check all that apply)

Personal Protective Equipment	Check box if applicable	Description
Gloves		Appropriate for solvent being used. (consult a glove selection guide)
Lab coats		Flame resistant
Suits
Aprons
Long pants
Close-toed shoes
Long sleeves
Safety glasses
Goggles
Face shields
Respirators (include cartridge type and cartridge change out schedule)
Hearing protection (include level of protection needed)
Special equipment (i.e., blast shields, special enclosures
Other PPE

9. WORK PRACTICE CONTROLS

10. MONITORING

None required for this procedure

11. SPILL AND ACCIDENT PROCEDURES

Wearing a flame-resistant lab coat, eye protection, and gloves, immediately cover spilled pyrophoric catalyst with water (squirt bottle) or Metal-X. Then thoroughly soak some paper towels with water. Use the wetted paper towels to mop up the spilled catalyst. Immediately place the used paper towels in the waste container designated for pyrophoric catalysts—do not allow the contaminated towels to dry in the air. Purge the waste container with inert gas and then cap tightly.

12. WASTE DISPOSAL PROCEDURES (include segregation of acids, bases, halogenated compounds, PPE, collection and transport procedures, proper documentation, regulations, etc.)

It is suggested that waste containers containing pyrophoric catalysts contain ample water to ensure the solids remain wetted. The container will be flushed with inert gas and then tightly capped. The container is designated for pyrophoric catalysts only, and no other types of waste can be added to it. Spent pyrophoric catalysts are generally designated as reactive waste and are handled accordingly.

13. STORAGE (check all that apply)

Ventilated enclosures

Refrigeration

Gas cabinet

Compliance with regulations

Expiration date:

Inventory:

Other:

Most vendor-supplied metal catalysts are not supplied in an activated state and are not pyrophoric until activated. Normal storage procedures can be applied. Raney metal catalysts are provided as water slurries to prevent ignition. These samples are stored in tightly capped containers to prevent them from drying out. Inspect routinely and segregate from flammable materials.

14. TRANSPORTATION PROCEDURES:

(e.g., secondary container for transport between and across laboratories; secondary containment for experimental apparatus)

Secondary container for transport between and across laboratories

Secondary containment for experimental apparatus

15. PEER REVIEW

16. VERIFICATION AND REVIEW

By signing below, you acknowledge that you have read, understand, and approve the SOP.

17. LIST OF REFERENCES (include Safety Data Sheets, Globally Harmonized System, any outside personnel consulted in preparation of document, peer reviewers, etc.)

High Risk Standard Operating Procedure Review and Modifications Log

Were modifications made to current SOP?	Yes No
If no, then list date of approval
Last reviewed by (please print)
If yes, then list and describe modifications

Were modifications made to current SOP?	Yes No
If no, then list date of approval
Last reviewed by (please print)
If yes, then list and describe modifications

Were modifications made to current SOP?	Yes No
If no, then list date of approval
Last reviewed by (please print)
If yes, then list and describe modifications

SCENARIO 3: TOXIC AND EXPLOSIVE GASES: HANDLING DIAZOMETHANE AND ALTERNATIVES

Overview: This scenario describes a situation where a graduate student wants to run a reaction that calls for diazomethane. After completing the hazard assessment checklist, she develops a High Risk SOP. Her advisor, who reviews the SOP, does not approve of the use of diazomethane and suggests an alternative compound (trimethylsilyl)diazomethane (TMSD).

SCENARIO:

An experienced student wants to use diazomethane as an alkylating agent in her reaction. Diazomethane has been flagged as highly hazardous because of its flammability, explosive potential, and toxicity as noted in sections 7 and 9 of the National Academies of Sciences, Engineering, and Medicine report, Chemical Laboratory Safety and Security. The student immediately recognizes that she will need to develop a High Risk SOP. She asks her advisor to review her SOP. He does not approve the SOP, even though the student followed and completed the correct steps.

Suggested solution:

The advisor recognized that diazomethane can be substituted with (trimethylsilyl)diazomethane (TMSD) because it is less likely to explode as it generates diazomethane in situ and may be used for the reaction. TMSD is commercially available in anhydrous hexanes or diethyl ether, and the respective Safety Data Sheets are available online. Although explosive accidents have not occurred with TMSD, TMSD is far from being a perfect surrogate. The toxicity of TMSD is still high, with at least two recorded deaths from inhalation.

High Risk Standard Operating Procedure Form

1. TITLE AND DESCRIPTION OF EXPERIMENT OR PROCESS: Toxic and Explosive Gases: Safe Handling of Diazomethane and Alternatives

2. PREPARER(S): [name]

3. LOCATION: Room 101 Chemistry Hall

4. AUTHORIZED PERSONNEL (WITH CONTACT INFORMATION)

a. PRINICIPAL INVESTIGATOR (PI)/SUPERVISOR: [name] (555) 854-9654

b. STUDENT(S)/TECHNICIAN(S)/OPERATOR(S): [name] (555) 202-2020

c. OTHERS TO BE NOTIFIED (e.g., other workers in the same laboratory, or other members of the research group): [name] (555) 333-4444

5. IDENTIFY ANY TRAINING NEEDS: No specific training required

6. DETAILED PROCESS DESCRIPTION See SDS for CAS Registry Number 18107-18-1

7. ENGINEERING CONTROLS (check all that apply and provide a detailed description)

Engineering Controls	Check box if applicable	Description
Ex. Glove box		Use inert air (N2 or Ar)
Fume hood or glove box
Special ventilation
HEPA filtered vacuum lines
Non-reactive containers
Pressure relief devices
Temperature control
Bench paper, pads, plastic-backed paper
Special signage
Safe sharp devices
Other safety devices used:

8. PERSONAL PROTECTIVE EQUIPMENT (check all that apply)

Personal Protective Equipment	Check box if applicable	Description
Gloves		Nitrile 8-mil gloves recommended. If contact is likely, then double glove using a second exam-grade nitrile glove first and the utility-grade nitrile glove second.
Lab coats		Flame resistant
Suits
Aprons
Long pants
Close-toed shoes
Long sleeves
Safety glasses
Goggles
Face shields
Respirators (include cartridge type and cartridge change out schedule)
Hearing protection (include level of protection needed)
Special equipment (i.e. blast shields, special enclosures
Other PPE

9. WORK PRACTICE CONTROLS

10. MONITORING

11. SPILL AND ACCIDENT PROCEDURES

12. WASTE DISPOSAL PROCEDURES (include segregation of acids, bases, halogenated compounds, PPE, collection and transport procedures, proper documentation, regulations, etc.)
After the diazomethane solution is quenched, dispose of it through normal waste streams.

13. STORAGE (check all that apply) Storage of diazomethane solutions is highly discouraged

Ventilated enclosures

Refrigeration

Gas cabinet

Compliance with regulations

Expiration date:

Inventory:

Other:

14. TRANSPORTATION PROCEDURES:

(e.g., secondary container for transport between and across laboratories; secondary containment for experimental apparatus)

n/a

15. PEER REVIEW

16. VERIFICATION AND REVIEW

By signing below, you acknowledge that you have read, understand, and approve the SOP.

17. LIST OF REFERENCES (include Safety Data Sheets, Globally Harmonized System, any outside personnel consulted in preparation of document, peer reviewers, etc.)

SDS for (trimethylsilyl)diazomethane—CAS Registry Number 18107-18-1

High Risk Standard Operating Procedure Review and Modifications Log

Were modifications made to current SOP?	Yes No
If no, then list date of approval
Last reviewed by (please print)
If yes, then list and describe modifications

Were modifications made to current SOP?	Yes No
If no, then list date of approval
Last reviewed by (please print)
If yes, then list and describe modifications

Were modifications made to current SOP?	Yes No
If no, then list date of approval
Last reviewed by (please print)
If yes, then list and describe modifications

SCENARIO 4: REAGENT STORAGE

Overview: This scenario describes a situation in which a laboratory manager in a large academic laboratory receives three requests from chemistry graduate students for chemical reagents:

• Sodium Azide, 5 g
• Piperonal, 500 g
• Diazald, 25 g

SCENARIO:

The University has a different level of experience and safety awareness with each of these reagents. Exemplary execution of the pre- and post-ordering activities and storage process for these three reagents is shown below:

Suggested Solution:

Sodium Azide: When the laboratory manager receives the request for sodium azide, he searches the chemical reagent inventory list and realizes that this reagent has not previously been ordered for use in the department. He accesses the vendor’s website to review the Safety Data Sheet (SDS) and notes warnings of acute toxicity (oral, dermal, inhalation), “Health Hazard” for respiratory sensitization, and “Environment” for hazard to the aquatic environment, both acute and chronic. Azides in combination with acid or acid vapors can form deadly hydrazoic acid, a toxic gas. Azides also present a severe explosion risk when shocked or heated. It is suggested that sodium azide be stored tightly in closed containers in a well-ventilated and dry area away from acid. Because of the explosive potential and safety and security concerns, sodium azide should be avoided in a synthesis if a reasonable alternative exists whenever possible. The student consults the literature and does not find an alternative that will work in the synthetic reaction. After reviewing the SDS and confirming that the reagent is not on the University’s Dual-Use Chemicals List, the laboratory manager places the order for this chemical reagent.

While waiting for the bottle of sodium azide to arrive from the vendor, the laboratory manager uses the Chemical Storage Matrix to identify the chemical’s storage requirements: Are there special temperature requirements? Does the reagent need to be segregated from other chemicals? Are there special security considerations? There are no special requirements for temperature to store sodium azide. Storage in standard ventilated room temperature reagent cabinets will segregate the chemical from acids (because acids are segregated). Therefore, the laboratory manager arrives at the conclusion that “Aggregated—Ventilated Room Temperature” in an area that is temperature and humidity controlled is the proper location for this reagent. Out of an abundance of caution, the laboratory manager stores sodium azide in a secondary container with Drierite (anhydrous sodium sulfate). For future reference, this reagent is added to the University’s list of chemical reagents with the storage designation “Aggregated—Ventilated Room Temperature” with secondary containment. When the student picks up the chemical reagent, the laboratory manager provides a copy of the Safety Data Sheet, notes the hazardous nature of the chemical, and recommends that the student speak with his or her professor before running the first reaction to discuss safe handling for the reaction. In that discussion, the student and professor agree that a Moderate Risk SOP should be drafted for the use of this reagent. While that SOP is being drafted, the student performs the initial probe reactions using sodium azide on a very small scale (< 10 mmol), mitigating the danger of this reaction.

Piperonal: Following the University’s SOP for chemical reagent management, the laboratory manager scans the University’s Dual-Use Chemicals List prior to ordering the chemical and notes that this reagent is on the list

because of its potential to be used for the synthesis of illicit drugs. Although the reagent has been used before at the University, there is presently no material available. The laboratory manager finds that piperonal is a volatile aldehyde that releases a vapor that can induce central nervous system depression. The laboratory manager also reviews the catalog of the chemical supplier and learns that this reagent is available in much smaller quantities than the 500 g bottle requested by the student. As a result, the laboratory manager alerts the student to the fact that this reagent is on the Dual-Use Chemical List and inquires whether 25 g will meet the student’s needs. The student explains that he recommended the 500 g bottle because the unit price at 500 g is one-quarter the unit price at 25 g. After the laboratory manager explains that the best practice guideline is to order the minimum quantity of dual-use chemicals, the student agrees that 25 g is sufficient for his research needs. The laboratory manager then emails the student’s professor as required by the SOP for reagent management to request authorization to order this dual-use reagent. The professor and the student discussed the use of this reagent at the previous day’s group meeting, so the professor immediately approves the request, and the laboratory manager places the order. Upon its arrival, the reagent is placed in a locked storage cabinet, which is ventilated at room temperature. The student is notified of the reagent’s arrival and is reminded that the reagent must be checked out and returned the same day so that it can be secured.

Diazald: Diazald is a common precursor for the generation of diazomethane. The laboratory manager is aware of the danger of diazomethane and of an alternative reagent to diazald. The laboratory manager emails the professor (and copies the student) asking for verification of the need for this chemical reagent. In this case, the professor was unaware that the student was approaching the chemical reaction using the diazald procedure for generation of diazomethane. The professor suggests that the student first try the reaction with (trimethylsilyl) diazomethane, a safer alternative. The laboratory manager searches the existing chemical inventory and finds a recently ordered bottle (2 M dissolved in diethyl ether) in one of the laboratory refrigerators. The student borrows the existing diazald and discusses prudent safeguards with another student in the laboratory with experience with the reagent before performing the reaction.

CHEMICAL STORAGE MATRIX