Trimethylsilyldiazomethane

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), trimethylsilyldiazomethane, which has an estimated vapor pressure of 1.19X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase trimethylsilyldiazomethane may undergo a hydrolysis reaction with atmospheric water vapor but may also be degraded by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 6 days(SRC), calculated from its rate constant of 2.58X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3) Particulate-phase trimethylsilyldiazomethane may be removed from the air by wet or dry deposition(SRC). Trimethylsilyldiazomethane does not contain chromophores that absorb at wavelengths >290 nm(4), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

/CASE REPORTS/ A 46 year-old male pharmaceutical chemist presented to the emergency department (ED) with progressive dyspnea. At noon on the prior day, as part of a chemical analysis, he had mixed 2 mL of acetone with 25 mL of L-Malic acid to which was added trimethylsilyldiazomethane (TSDM) dissolved in n-hexane. After 1 hour this mix was combined with an inert gas and a small amount of methylene chloride under a fume hood that was later reported to be nonfunctioning. Although he experienced no immediate mucous membrane irritation, 8 hours post-exposure he developed cough, pleuritic chest pain, hemoptysis, and progressive shortness of breath; by 15 hours, he presented to the ED in respiratory distress, hypoxic (PaO2 67), hypercarbic (PaCO2 46), and acidemic (pH 7.26). A chest radiograph showed an acute lung injury pattern. By 23 hours he required intubation. At 26 hours postexposure he developed profound bradycardia, refractory hypotension, and asystole. Diazomethane (DM) inhalation is known to cause fatal pulmonary edema without an immediate irritant prodrome and with a similar time course to this case. Structural modification of DM with an added trimethylsilyl group makes TSDM less explosive, but its propensity for lung injury is unclear. The chemical admixture as described in this case may have liberated nitrogen gas, but this should not have led to pulmonary injury; nitrogen dioxide should not have evolved. The toxicity may stem from residual DM present in the reagent or a direct effect of TSDM, its metabolites or breakdown products, or potential intracellular formaldehyde formation. The temporal relationship to exposure with inadequate ventilation and clinical effects similar to the analogue toxicant DM support a causal relationship between TSDM and acute lung injury.

Trimethylsilyldiazomethane's production and use as a reagent in organic synthesis(1) for the esterification of carboxylic acids, etherifcation of sterically hindered alcohols and as an alternative to diazomethane(2) may result in its release to the environment through various waste streams(SRC).

The rate constant for the vapor-phase reaction of trimethylsilyldiazomethane with photochemically-produced hydroxyl radicals has been estimated as 2.58X10-12 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 6 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Trimethylsilyldiazomethane reacts rapidly with water, and therefore hydrolysis is not expected. Trimethylsilyldiazomethane does not contain chromophores that absorb at wavelengths >290 nm(2), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Occupational exposure to trimethylsilyldiazomethane may occur through inhalation of solvent vapors in which trimethylsilyldiazomethane is dissolved during organic syntheses. Dermal contact with solutions of this compound in organic solvents may also occur at workplaces where trimethylsilyldiazomethane is produced or used. The general population is not likely to be exposed to trimethylsilyldiazomethane since it is primarily used in a laboratory setting. (SRC)

Trimethylsilyldiazomethane's production and use, primarily in a laboratory setting, as a reagent in organic synthesis for the esterification of carboxylic acids may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 1.19X10-5 mm Hg at 25 °C indicates trimethylsilyldiazomethane will exist in both the vapor phase and particulate phase in the atmosphere. Vapor-phase trimethylsilyldiazomethane may react with atmospheric water vapor and may be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 6 days. Particulate-phase trimethylsilyldiazomethane may be removed from the air by wet or dry deposition. Trimethylsilyldiazomethane does not contain chromophores that absorb at wavelengths >290 nm, and therefore is not expected to be susceptible to direct photolysis by sunlight. Since trimethylsilyldiazomethane reacts rapidly with polar functional groups, volatilization from water or soil are not relevant environmental fate processes. Similarly, adsorption to soil/sediments, bioconcentration, and biodegradation are not expected due to the potential for decomposition under environmental conditions. Occupational exposure to trimethylsilyldiazomethane may occur through inhalation of solvent vapors in which trimethylsilyldiazomethane is dissolved during organic syntheses. Dermal contact with solutions of this compound in organic solvents may also occur at workplaces where trimethylsilyldiazomethane is produced or used. The general population is not likely to be exposed to trimethylsilyldiazomethane since it is primarily used in a laboratory setting. (SRC)

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/