General Description
A clear colorless liquid with a faint odor similar to ammonia. About the same density as water. Flash point 145°F. Vapors heavier than air. May by toxic by skin absorption. May irritate eyes and skin.
Reactivity Profile
DIMETHYLACETAMIDE(127-19-5) is an amide. Incompatible with oxidizing agents and halogenated compounds. Exothermic reactions occur with carbon tetrachloride and hexachlorocyclohexane. DIMETHYLACETAMIDE(127-19-5) can react violently in the presence of iron. Special Hazards of Combustion Products: Emits carbon oxides, nitrogen oxides, and dimethylamine when heated to decomposition.
Air & Water Reactions
Water soluble.
Health Hazard
Liquid causes mild irritation of eyes and skin. Ingestion causes depression, lethargy, confusion and disorientation, visual and auditory hallucinations, perceptual distortions, delusions, emotional detachment, and affective blunting.
Fire Hazard
This chemical is combustible.
Description
Dimethylacetamide (DMAC) is a synthetic organic compound
that is produced from a reaction of dimethylamine and acetic
acid or acetic anhydride. It is a colorless to yellow liquid with
a faint odor resembling ammonia. DMAC has similar density
to water and is miscible with water and organic substances. This
organic compound is commonly associated with many industrial
uses, either as a starting material or an intermediate.
DMAC is a good solvent that is used in polymer dissolution,
especially in the fiber industry. Historically, DMAC was also
tested as a possible antineoplastic agent in a phase 1 study
involving 17 patients. However, liver and central nervous
system (CNS) toxicity associated with DMAC was observed and
these patients had altered mental states, resulting in no further
drug development.
Physical properties
Clear, colorless liquid with a weak, ammonia-like odor. Odor threshold concentration is 46.8 ppmv
(Leonardos et al., 1969).
Application
N,N-Dimethylacetamide is primarily used as an industrial solvent and intermediate in the manufacture of pharmaceuticals, fine chemicals, agrochemicals, polymers, and resins. It is also used as a spinning solvent in the production of fibers of various polymers, including acrylic, polyurethane, polyurea copolymer, and meta-aramid. Moreover, this aprotic dipolar solvent is also used in X-ray and photographic products and in the production of polyimide films. The polyimide films are produced for a variety of industries, including consumer electronics, solar photovoltaic and wind energy, aerospace, automotive, and industrial applications. N,N-Dimethylacetamide has other minor uses, including removal of ink, stripping of paint, and also for laboratory use.
Definition
ChEBI: A member of the class of acetamides that is acetamide in which the hydrogens attached to the N atom have been replaced by two methyl groups respectively. Metabolite observed in cancer metabolism.
Preparation
N,N-Dimethylacetamide is prepared by reaction of dimethylamine with acetic acid, acetic anhydride, or acetate esters. Heating dimethylamine acetate with, or without a catalyst affords N,N-Dimethylacetamide. Reaction of dimethylamine with acetate esters requires a catalyst; sodium methoxide is typically used.
Production Methods
Dimethylacetamide is manufactured from acetic acid and dimethylamine in a closed system.
Pharmaceutical Applications
Dimethylacetamide is used as a solvent in oral and injectable pharmaceutical formulations. It has been used as a cosolvent to solubilize poorly soluble drugs. The use of dimethylacetamide has also been investigated as a vehicle for the parenteral delivery of relatively small peptides.
The use of solvents such as dimethylacetamide has been shown to influence the size and rate of release of norfloxacin from nanoparticles.
Dimethylacetamide has also been used in topical formulations and has been evaluated as a permeation enhancer for transdermal drug delivery.
Industrial uses
Dimethylacetamide is a powerful industrial solvent, the uses of which are very similar to those of dimethylformamide (Siegle, 1980). Its strong solvent action renders it particularly useful in the manufacture of films and fibers and as a solvent for polyacrylonitrile, polyvinyl chloride, polyamides, cellulose derivatives and polystyrenes and in coatings and adhesive formulations. Dimethylacetamide dissolves many inorganic salts.
Safety
Dimethylacetamide is used in pharmaceutical preparations as a solvent in parenteral formulations and is generally regarded as a nontoxic material when used as an excipient. Animal toxicity studies indicate that dimethylacetamide is readily absorbed into the bloodstream following inhalation or topical application. Repeated exposure to dimethylacetamide may be harmful and can result in liver damage. High intravenous doses (>400mg/kg/day for 3 days) may be hallucinogenic.
LD50 (rabbit, SC): 9.6g/kg(11) LD50 (rat, IP): 2.75g/kg LD50 (rat, IV): 2.64g/kg LD50 (rat, oral): 4.93g/kg LD50 (mouse, inhalation): 7.2g/kg LD50 (mouse, IP): 2.8g/kg
Potential Exposure
Drug,Mutagen; Reproductive Effector; Primary Irritant.Dimethylacetamide is used primarily as a solvent for synthetic and natural resins, especially acrylic fibers and spandex. About 15% of dimethylacetamide production is used tomake alkyl (C12-14) dimethylamine oxide (a surfactant) andrubber chemicals. Dimethylacetamide is also used as anextraction solvent for butadiene manufacture.
First aid
If this chemical gets into the eyes, remove anycontact lenses at once and irrigate immediately for at least15 min, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts theskin, remove contaminated clothing and wash immediatelywith soap and water. Seek medical attention immediately. Ifthis chemical has been inhaled, remove from exposure,begin rescue breathing (using universal precautions, including resuscitation mask) if breathing has stopped and CPRif heart action has stopped. Transfer promptly to amedical facility. When this chemical has been swallowed,get medical attention. Give large quantities of water andinduce vomiting. Do not make an unconscious personvomit.
Carcinogenicity
DMAC was not carcinogenic in
rats administered 100, 300, or 1000 mg/kg/day in drinking
water for 2 years. Rats and mice were exposed by
inhalation to 0, 25, 100, or 350 ppm DMAC for 6 h/day,
5 days/week for 18 months (mice) or 2 years (rats). DMAC
was not oncogenic under these conditions in either the rat or
the mouse.
Environmental Fate
Chemical/Physical. Releases toxic fumes of nitrogen oxides when heated to decomposition (Sax
and Lewis, 1987).
Metabolism
Gas Chromatographie analysis of the urine of rats which had received dimethylacetamide by the subcutaneous route indicated the presence of N-methyl-acetamide and acetamide (Barnes and Ranta, 1972). Both metabolites were also found by the same authors in incubation mixtures of dimethylacetamide with rat liver homogenate. N-Methylacetamide was detected in the urine of human volunteers who had inhaled dimethylacetamide or absorbed dimethylacetamide vapor through the skin (Maxfield et al 1975). Measurement of the amount of the metabolite N-methylacetamide excreted by individuals exposed to dimethylacetamide vapors with or without face masks which allowed the inhalation of air free of dimethylacetamide indicated that more dimethylacetamide was absorbed through the lungs than through the skin. Interestingly, in this study, only 2-10% of the amount of dimethylacetamide inhaled was recovered in the urine in the form of N-methylacetamide. It has been suggested that the major urinary metabolite of the analogous dimethylformamide is N-(hydroxymethyl)-N-methylformamide and not N-methylformamide, since the carbinolamide decomposes on the gas chroma-tography column (to N-methylformamide) but is relatively stable in aqueous solution (Kestell et al 1986). In analogy, it would be logical to assume that the N-methylacetamide found in the urine after exposure to dimethylacetamide really arose from chemical breakdown of N-(hydroxymethyl)-N-methylacetamide during the analytical process. This contention, however, remains to be proven.
storage
Dimethylacetamide should be stored in an airtight container, protected from light, in a cool, dry place. Dimethylacetamide has an almost unlimited shelf-life when kept in closed containers and under nitrogen. It is combustible.
Shipping
This material is not covered in DOT’sPerformance-Oriented Packaging Standards. It may,however, be classified as a combustible liquid, n.o.s. Thisclass requires no shipping label. It falls in Hazard Class 3[each reference to a Class 3 material is modified to read“COMBUSTIBLE LIQUID” when that material is reclassified in accordance with y173.150 (e) or (f) of this subchapter or has a flash point above 60.5℃/141°F but below93℃/200°F] and Packing Group III. The symbol “D” identifies proper shipping names which are appropriate fordescribing materials for domestic transportation but may beinappropriate for international transportation under the provisions of international regulations (e.g., IMO, ICAO). Analternate proper shipping name may be selected when eitherdomestic or international transportation is involved.
Purification Methods
Shake the amide with BaO for several days, reflux it with BaO for 1hour, then fractionally distil it under reduced pressure. Store it over molecular sieves. [Beilstein 4 IV 180.]
Toxicity evaluation
Little data on the metabolism of DMAC are available in the
literature. Hepatotoxicity of DMAC is believed to be metabolism
dependent. From its metabolic activation (by cytochrome
P450s and probably CYP2E1), reactive species and free radical
metabolites are produced and readily attack the heme prosthetic
group of the liver, leading to suicidal hepatic enzyme
inactivation.
Incompatibilities
Dimethylacetamide is incompatible with carbon tetrachloride, oxidizing agents, halogenated compounds, and iron. It attacks plastic and rubber. Contact with strong oxidizers may cause fire.
Regulatory Status
Included in the FDA Inactive Ingredients Database (IM injections, IV injections and infusions). Included in parenteral medicines licensed in the UK.
