Standard Operating Procedure
Settlement Class: Pyrophorics
Methyl Methyl Grignard Reagent Solutions
This is an SOP template and is not complete until: 1) lab specific information is entered into the
box below 2) lab specific protocol/procedure is added to the protocol/procedure section and
3) SOP has been signed and dated by the PI and relevant lab personnel.
Print a copy and insert into your
Laboratory Safety Manual and Chemical Hygiene Plan.
Refer to instructions for assistance.
Department:
Chemistry
Date SOP was written:
11/11/2012
Date SOP was approved by PI/lab supervisor:
Principal Investigator:
Richmond Sarpong
Internal Lab Safety Coordinator/Lab Manager:
Lab Phone:
1/13/2013
Rebecca Murphy
510-643-2485
Office Phone:
510-643-6312
Emergency Contact:
Richmond Sarpong 626-644-2407
Location(s) covered by this SOP:
Latimer 834, 836, 837, 838, 839, 842, 844, 847, 849,
907
(Name and Phone Number)
(Building/Room Number)
Type of SOP:
☐ Process
☒Hazardous Chemical
☐ Hazardous Class
Purpose
Methyl Grignard reagent solutions are all highly flammable and some may be pyrophoric and
spontaneously ignite in contact with air. The solutions are corrosive. They react violently with water and
vapors may form explosive mixture with air. They widely employed as potent nucleophiles and strong
bases in organic synthesis, both industrially and in the laboratory.
Methyl Grignard reagents are powerful nucleophiles, strong bases and even occasionally reductants,
depending on the other reactants. Methyl Grignard reagents add to carbonyl compounds such as
aldehydes yielding a magnesium alkoxide derivative prior to workup. Methyl Grignard reagents are
typically used in the synthesis of specific alcohols by addition to aldehydes, ketones and esters.
Methyl Grignard Reagent Solutions.
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SOP Template developed by The UC Center for Laboratory Safety
Date: 12/18/2012
Examples of Methyl Grignard Reagents
Methyl Grignard alkylmagnesium halides. The halide can be bromide, chloride or
iodide. The solvent can be t-butyl methyl ether, diethyl ether, tetrahydrofuran, or
toluene and the molarities typically range from 1 to 3 molar.
Physical & Chemical Properties/Definition of Chemical Group
CAS#: various. Examples from the title list include 1730-25-2, 677-22-5, 931-51-1, 2386-64-3, 4301-148, 1068-55-9, 75-16-1, 100-58-3, 2234-82-4, 1826-67-1
Class: Pyrophoric, Flammable, Corrosive
Molecular Formula: Variable: CH3Mg-X
Form (physical state): Liquid
Color: Colorless
Boiling point: N/A
Potential Hazards/Toxicity
Material is extremely destructive to tissue of the mucous membranes and upper respiratory tract, eyes,
and skin. Inhalation may provoke the following symptoms: spasm, inflammation and edema of the
bronchi, spasm, inflammation and edema of the larynx. Aspiration or inhalation may cause chemical
pneumonitis and pulmonary edema. Symptoms of exposure may include burning sensation, coughing,
wheezing, laryngitis, shortness of breath, headache, nausea, and vomiting. May be harmful if absorbed
through the skin. Can cause burns to the skin and eyes.
Engineering Controls
1. Methyl Grignard reagents should be used in a glove box filled with inert gas, or in a closed
system in a certified fume hood.
2. Keep the material under inert atmosphere (e.g., nitrogen, argon) when not in use.
3. Only when absolutely necessary to transfer larger quantities of pyrophorics, use an
appropriately-designed, engineered system that is tested and properly used.
Personal Protective Equipment (PPE)
Respirator Protection
If a respirator is the sole means of protection, please use a full-face supplied air respirator.
Respirators should be used only under any of the following circumstances:
 As a last line of defense (i.e., after engineering and administrative controls have been
exhausted).
 When Permissible Exposure Limit (PEL) has exceeded or when there is a possibility that PEL will
be exceeded.
 Regulations require the use of a respirator.
Methyl Grignard Reagent Solutions.
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SOP Template developed by The UC Center for Laboratory Safety
Date: 12/18/2012
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An employer requires the use of a respirator.
There is potential for harmful exposure due to an atmospheric contaminant (in the absence of
PEL)
As PPE in the event of a chemical spill clean-up process
Hand Protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique (without
touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves
after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.
NOTE: Lab-specific and chemical-specific information on glove selection may be included in the
Protocol/Procedure section. Refer to glove selection from the link below:
For glove selection, go to: http://ehs.berkeley.edu/hs/63-laboratory-safety/94-glove-selection-andusage.html
Lab personnel intending to use/wear a respirator mask must be trained and fit-tested by EH&S. This is a
regulatory requirement.
NOTE: Lab-specific and chemical-specific information on glove selection may be included in the
Protocol/Procedure section. Nomex-and-leather flight gloves over chemically resistant gloves are
recommended in the UC Berkeley Office of Environmental Health and Safety document “Safe Use of
Pyrophoric and Water Reactive Reagents”. See also, EHS&S document entitled “Glove Selection and
Usage.”
http://www.ehs.berkeley.edu/hs/63-laboratory-safety/94-glove-selection-and-usage.html
http://www.ehs.berkeley.edu/hs/126-standard-operating-procedures-sop.html
Eye Protection
Safety glasses (goggles and/or full face shield during activities which pose a splash hazard).
Skin and Body Protection
A flame resistant lab coat must be worn. Full length pants or equivalent as well as closed toe shoes must
be worn.
Hygiene Measures
Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling
Methyl Grignard reagents.
First Aid Procedures
If Inhaled
Move person into fresh air. If breathing is difficult, give oxygen. Do NOT use mouth-to-mouth
resuscitation. Get medical attention immediately.
In Case of Skin Contact
Immediately flush skin with plenty of water for at least 15 minutes while removing contaminated clothing
and shoes. Wash clothing before reuse. Thoroughly clean shoes before reuse. Get medical attention
immediately.
In Case of Eye Contact
Methyl Grignard Reagent Solutions.
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SOP Template developed by The UC Center for Laboratory Safety
Date: 12/18/2012
Check for and remove any contact lenses. Immediately flush eyes with plenty of water for at least 15
minutes. Get medical attention immediately
If Swallowed
Do NOT induce vomiting unless directed to do so by medical personnel. If victim is conscious and alert,
rinse mouth with 2-4 cupfuls of water. Never give anything by mouth to an unconscious person. Get
medical attention immediately.
Special Handling and Storage Requirements
Working Alone
Certain extremely hazardous operations should not be performed if the PI or Lab Safety Contact(s) are
not present. Never work alone with extremely hazardous materials/operations. See the
Protocol/Procedure section below for specific prohibitions (if any) on working alone.
NOTE: The UC Berkeley Office of Environmental Health and Safety document “Safe Use of Pyrophoric
and Water Reactive Reagents” specifies not to work alone or during off hours, when there are few people
around to help. http://www.ehs.berkeley.edu/hs/126-standard-operating-procedures-sop.html
Precautions for Safe Handling
 Avoid contact with skin and eyes.
 Avoid inhalation of vapor or mist.
 Design a quenching scheme for residual materials prior to using pyrophoric materials.
 Never use water to quench the material itself or a reaction where a pyrophoric reagent is used.
 Begin quenching with a low reactivity quenching agent and slowly add more reactive quenching
agents. For example, first quench residual sodium metal with isopropanol and then add ethanol to the
mixture.
 Design your experiment to use the least amount of material possible to achieve the desired result.
 It is better to do multiple transfers of small volumes than attempt to handle larger quantities. Before
transferring, make sure that the material is at room temperature.
 Avoid formation of dusts and aerosols
 Provide appropriate exhaust ventilation at places where airborne hazardous materials may be
generated.
 Use explosion-proof equipment.
 Keep away from sources of ignition and combustible materials such as open flames, non-explosionproof hot plates, paper towels and KimiwipesTM - No smoking.
 Take measures to prevent the build-up of electrostatic charge.
 Eliminate or substitute a less hazardous material when possible.
 Verify your experimental set-up and procedure prior to use.
 Inform colleagues that this material will be used and where. Label the work area with a sign saying
"Pyrophorics In-Use Area".
 Ensure that the area is properly equipped with a properly functioning eye wash/safety shower within
ten seconds of travel.
 Never use water to extinguish fires caused by water reactive materials. Be sure to use a an
appropriate fire extinguisher for the materials being used.
NOTE: See a more details on safe handling in the UC Berkeley Office of Environmental Health and
Safety documents “Safe Use of Pyrophoric and Water Reactive Reagents” and “Quenching of Pyrophoric
Substances”. http://www.ehs.berkeley.edu/hs/126-standard-operating-procedures-sop.html
Conditions for Safe Storage.
Methyl Grignard Reagent Solutions.
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SOP Template developed by The UC Center for Laboratory Safety
Date: 12/18/2012
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Keep container tightly closed in a dry and well-ventilated place.
Containers that are opened must be carefully resealed and kept upright to prevent leakage.
Minimize dust generation and accumulation.
Since Methyl Grignard reagents react violently with water, never allow product to get in contact with
water or water-based compounds during storage.
Store and handle under inert gas (Noble gases such as Nitrogen, Argon etc.).
Protect from moisture and humid atmospheres.
Avoid extremes in temperature and direct sunlight.
Avoid storing next to strong oxidizing agents, fluorine, chlorine, and perchlorates.
Incompatibilities with Other Materials: carbonyl containing compounds, acidic compounds.
Hazard communication label on the container must read ‘Water Reactive’. W
Do not leave the container on the bench top - even momentarily.
Do not leave the container near a lab sink, emergency eyewash or safety shower.
Keep in a dry place (such as a desiccator or a dry box or glove box).
Use/purchase only amount that is needed in a reasonable amount of time. Use small quantities
whenever possible.
Store in a separate secondary container and label the material clearly.
Follow any substance-specific storage guidance provided in Safety Data Sheet documentation.
Monitor your inventory closely to assure that you have tight control over your material.
Wash hands and arms with soap and water after handling.
Minimize dust generation and accumulation.
At the end of each project, thoroughly inspect the area for residual reactive material.
Spill and Accident Procedure
Fire-fighting & Extinguishing media
Prior to use, review the Safety Data Sheet for the proper fire extinguisher to use with the given material
Acceptable fire extinguishing media include Metal X, soda ash (lime) or dry sand to respond to small fires, and
an ABC extinguisher for large fires. The extinguishing media should be located near where the pyrophoric work
is occurring. DO NOT use water to attempt to extinguish a pyrophoric/reactive material fire as it can enhance
the combustion of some of these materials, e.g. metal compounds, and do not use water or CO2 extinguishers
on an organolithium fire. A small beaker of Metal X/LithX, dry sand or soda ash (lime) in the work area is useful
to extinguish any small fire that occurs at the syringe tip and to receive any last drops of reagent from the
syringe. . In general, an ABC dry powder extinguisher will put out the fire, but the pyrophoric reagent may
reignite.
Special protective equipment for fire-fighters
Wear Self-Contained Breathing Apparatus (SCBA) for fire-fighting if necessary.
Personal precautions
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Avoid dust formation.
Ensure adequate ventilation.
Remove all sources of ignition and combustion.
Evacuate personnel to safe areas.
Environmental precautions
Do not let product enter drains.
Methyl Grignard Reagent Solutions.
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SOP Template developed by The UC Center for Laboratory Safety
Date: 12/18/2012
Methods and materials for containment and cleaning up
 Pick-up and dispose of as hazardous waste without creating dust.
 Do not flush with water or bring in contact with moisture.
 Keep in suitable, tightly closed containers for disposal.
Chemical Spill Dial 911
Spill – Assess the extent of danger. Help contaminated or injured persons. Evacuate the spill area.
Avoid breathing vapors. If possible, confine the spill to a small area using a spill kit or absorbent material.
Keep others from entering contaminated area (e.g., use caution tape, barriers, etc.).
Small (<1 L) – If you have training, you may assist in the clean-up effort. Use appropriate personal
protective equipment and clean-up material for chemical spilled. Double bag spill waste in clear plastic
bags, label and take to the next chemical waste pick-up.
Large (>1 L) – Dial 911 and 510-642-9090 for assistance.
Chemical Spill on Body or Clothes – Remove clothing and rinse body thoroughly in emergency shower
for at least 15 minutes. Seek medical attention. Notify supervisor and EH&S immediately. Follow up with
a call to 510-642-9090 to report the incident.
Medical Emergency Dial 911
Life Threatening Emergency, After Hours, Weekends and Holidays – Dial 911 or go to
the nearest emergency room. Note: All Serious injuries must be reported to EH&S within 8 hours.
Non-Life Threatening Emergency – Go to the Occupational Health Facility (OHF). After hours go
to the nearest emergency room. Note: All serious injuries must be reported to EH&S within 8 hours.
Needle Stick/Puncture Exposure (as applicable to chemical handling procedure) – Wash the
affected area with antiseptic soap and warm water for 15 minutes. For mucous membrane exposure,
flush the affected area for 15 minutes using an eyewash station. Page the needle stick nurse \ and then
enter your extension. After hours go to the nearest emergency room. Note: All needle stick/puncture
exposures must be reported to EH&S within 8 hours.
Decontamination/Waste Disposal Procedure
Wearing proper PPE, decontaminate equipment and bench tops using procedures done in cooperation
with site EHS&S. Dispose of any pyrophoric and water reactive waste materials and any other
disposables contaminated with these materials as hazardous waste.
NOTE: Lab-specific information on decontamination/waste disposal may be included in the
Protocol/Procedure section. See the EH&S Fact Sheet, “Hazardous Waste Management” for general
instructions on procedures for disposing of hazardous waste.
http://ehs.berkeley.edu/hm/279-new-hazardous-waste-program-hwp.html.
Label Waste
Label all containers with the label provided at http://ehs.berkeley.edu/hm/279-new-hazardous-waste-programhwp.html. See the EH&S Fact Sheet, “Hazardous Waste Management” for general instructions on
procedures for disposing of hazardous waste.
Methyl Grignard Reagent Solutions.
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SOP Template developed by The UC Center for Laboratory Safety
Date: 12/18/2012
Store Waste
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Store hazardous waste using procedures done in cooperation with site EH&S.
Waste must be under the control of the person generating & disposing of it
Dispose of Waste
 Dispose of regularly generated chemical waste within 6 months
 Call EH&S for questions
 Empty Containers
o Dispose as hazardous waste if it once held extremely hazardous waste (irrespective of
the container size)
o Consult waste pick-up schedule
Prepare for transport to pick-up location
 Check on-line waste tag
 Write date of pick-up on the waste tag
 Use secondary containment
 Dispose of regularly generated chemical waste within 6 months
 Call EH&S for questions
Safety Data Sheet (SDS) Location
SDS can be accessed online at http://ucmsds.com
For detailed information on properties, safe handling procedures, methods of synthesis, analysis,
and reactivity, see: Handbook of Methyl Grignard Reagents G. Silverman and P. Rakita, ed., Marcel
Dekker, 1996, 736 pp.
For detailed information on safe handling of air sensitive reagents, see:
http://www.sigmaaldrich.com/etc/medialib/docs/Aldrich/Bulletin/al_techbull_al134.Par.0001.File.tmp/al_te
chbull_al134.pdf
Methyl Grignard Reagent Solutions.
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SOP Template developed by The UC Center for Laboratory Safety
Date: 12/18/2012
Protocol/Procedure for Methyl Grignard Reagents
CAS #(s): 75-16-1, 676-58-4, 917-64-6
Preparation
Lab-specific
Information
Procedure/Use
Nucleophilic
addition into
carbonyl groups
or as a base
Eliminate incompatible materials from potential spill area.
Know the location of the nearest fire extinguisher, eyewash, and safety shower before beginning work.
Never work alone. Make sure there is another worker present who is also trained on the Methyl Grignard
Reagents SOP.Use spark-proof and explosion proof equipment.
Handle under nitrogen and protect from moisture. Avoid extreme temperatures and direct sunlight.
Scale
Engineering
Controls/Equipment
PPE (eye, face, gloves, clothing)
Up to 15 mL
by syringe.
All work using Methyl
Grignard Reagents must be
performed in a ventilated
fume hood with a chemical
resistant surface.
Eye protection: Wear tight-fitting
safety goggles or safety glasses
with side shields.
Use
cannula
transfer if
greater than
15 mL
Eliminate ignition sources
such as open flames, hot
surfaces, steam baths,
static electricity, and
operation of mechanical
and electrical equipment
that is not intrinsically safe.
Face protection: Wear a face
shield when not protected by a
lab hood sash
Gloves: Handle with gloves.
Gloves must be inspected prior to
use. Use proper glove removal
technique (without touching
glove's outer surface) to avoid
skin contact with this product.
Dispose of contaminated gloves
after use in accordance with
applicable laws and good
laboratory practices. Wash and
dry hands after use.
Clothing: Wear fire/flame
resistant lab coat (100% cotton
based); cotton based
clothing/attire; full length pants or
equivalent; and close-toed, close-
Methyl Grignard Reagent Solutions.
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SOP Template developed by The UC Center for Laboratory Safety
Date: 12/18/2012
Procedure Steps and Special
Precautions for this Procedure
There are two options for the handling
of Methyl Grignard reagents. The first
option is the use of a syringe and
needle, the second is to transfer using a
cannula. For smaller amounts of
reagent, the preferred technique is to
use a syringe and needle, while a
cannula transfer is safer and more
practical for amounts >15 mL. See
http://www.sigmaaldrich .com/
etc/medialib/docs/Aldrich/Bulletin/
altechbullal134.Par.0001.File.tmp/al_te
chbull_al134.pdf for a detailed
procedure on proper Schlenk
technique.
Proper syringe/needle transfer is as
follows:
All glassware and solvents should be
dried prior to the treatment with any
Methyl Grignard reagent. Flame-dried
glassware which has been cooled under
an inert atmosphere just before use is
ideal. Upon charging a dry flask with
dry reagents/solvents and reaching the
desired temperature, the appropriate
Methyl Grignard reagent can be added.
heeled shoes.
The Methyl Grignard reagent is
contained in a Sure-Seal bottle, the
septum of which can be pierced by
clean, dry needle fitted to a Schlenk line
which is supplying an inert gas. If the
bottle does not have a Sure-Seal, seal
off the top of the bottle with a septum.
This line is used to keep the reagent
under a blanket of inert gas during the
entire process. The inert gas flow is
adjusted by monitoring of the oil
bubbler on the Schlenk line. A clean,
dry reagent needle (<16 gauge) with
the appropriate size syringe is used to
pierce the septum and inert gas is
drawn in to the syringe, then the
needle is removed and the gas inside is
expelled to the atmosphere. This
process is repeated several times,
piercing the same hole in the septum,
to remove most air from the needle
Methyl Grignard Reagent Solutions.
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SOP Template developed by The UC Center for Laboratory Safety
Date: 12/18/2012
and syringe. Upon purging the needle
appropriately, the tip is submerged
below the level of reagent and the
required amount is drawn up into the
syringe. Be careful to hold the end of
the plunger as well as the joint where
the needle and syringe meet. If either
of these comes apart the reagent will
come out.
Once the desired amount of Methyl
Grignard reagent has been drawn into
the syringe, the tip of the needle is
pulled above the level of reagent, and
the plunger is pulled out slightly to
draw a blanket of inert gas into the
needle. The needle is then removed
from the reagent bottle and quickly
pierced into the septum of the reaction
flask. At this point, the Methyl
Grignard reagent is dispensed, usually
slowly to control heat evolution. Be
careful to hold the needle and syringe
together, as applying force to dispense
the reagent can cause them to separate
and expose the reagent to moisture.
Once the addition of reagent is
complete, the needle can be removed
from the reaction flask. The excess
reactive reagent can be expelled into a
beaker of sand or onto a chunk of dry
ice. After the excess reagent has been
expelled, the needle can be rinsed with
Methyl Grignard Reagent Solutions.
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SOP Template developed by The UC Center for Laboratory Safety
Date: 12/18/2012
hexanes multiple times, then water.
Clean the needle immediately after use
to prevent clogging. To close the
reagent bottle, simultaneously place a
piece of tape over the hole formed by
the needle while removing it from the
bottle. This should seal the bottle and
keep air and/or moisture from entering.
Replace the cap and wrap the outside
with parafilm to further ensure safe
storage.
Notes
Initials of
individuals using
this procedure
Any deviation from this SOP requires approval from PI.
Methyl Grignard Reagent Solutions.
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SOP Template developed by The UC Center for Laboratory Safety
Date: 12/18/2012
Documentation of Training (signature of all users is required)
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Prior to conducting any work with Methyl Grignard Reagents designated personnel must provide
training to his/her laboratory personnel specific to the hazards involved in working with this
substance, work area decontamination, and emergency procedures.
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The Principal Investigator must provide his/her laboratory personnel with a copy of this SOP and a
copy of the SDS provided by the manufacturer.
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The Principal Investigator must ensure that his/her laboratory personnel have attended appropriate
laboratory safety training or refresher training within the last one year.
I have read and understand the content of this SOP:
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Methyl Grignard Reagent Solutions.
Identification
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SOP Template developed by The UC Center for Laboratory Safety
Date: 12/18/2012