DMF is a risk of explosion in five cases - part 1

Although DMFS are commonly used, many people may not fully understand the nature of DMFS. Previously, we reported that there is an explosion risk when DMF and NaH are used. For details, see: Is it dangerous for NaH to use DMF solvent? However, DMF is not compatible with many types of substances, including acids, bases, halogens, oxidants and reducing agents, which can cause safety accidents if not carefully. Recently, Organic Process Research & Development, a journal of the American Chemical Society (ACS), published another review of the safety of DMF, reminding Organic chemists of the potential hazards of DMF.

N, N-dimethylformamide (DMF) (CAS No. 68-12-2, boiling point 153°C) is a clear colorless liquid with a light amine flavor and is often used as a polar aprotic solvent because of its ability to dissolve most organic and inorganic substances, and is widely used as a catalyst for various chemical transformations and as a donor for the synthesis of many functional groups. DMF is stable at ambient temperatures, but undergoes slow decarbonylation near its boiling point of 153 ° C to release Me2 NH and CO. Therefore, distillation of DMF is usually performed at reduced pressure and at lower temperatures below its boiling point.

DMF can be used as multifunctional block in organic synthesis

Potential safety risks of DMF in the presence of acid

DMF is hydrolyzed in the presence of acid to yield Me2NH and formic acid (HCO2H), which can be used as a way to prepare Me2NH "in situ" to achieve a variety of chemical transformations. However, in the presence of acids (especially strong acids), hydrolysis of DMF can be dangerous because the hydrolysate HCO2H further decomposes, releasing non-condensable gases such as CO, carbon dioxide (CO2), H2, etc. If the reaction system is not properly vented and inerted, it may lead to overpressure or even fire in the reactor, greatly increasing the severity of the danger. Sulfur trioxide (SO3) -DMF complex has been widely used as a sulfonation reagent and has been used in large-scale n-sulfation. However, a bottle of SO3-DMF complex has reportedly exploded during storage. Although the exact root cause has not been determined, it is suspected that SO3 reacts with water to form sulfuric acid (H2SO4), which subsequently decomposes the DMF to release CO and other products. DSC evaluation of so3-DMF complex samples at air atmosphere indicated that two distinct exothermic events occurred at 114 and 228°C. The energy release of these two exothermic events was -254 and -646 J/g, respectively.

Potential safety risks of DMF when alkali exists

In the presence of strong bases such as potassium hydroxide (KOH), sodium hydroxide (NaOH) or calcium hydroxide (CaH2), pure DMF will decompose significantly and form Me2NH in situ after prolonged exposure at ambient temperature.

DMF is used for nucleophilic aromatic substitution of aromatic fluorides and chlorides with the aid of hydroxides.

The in situ Me2NH formed by decomposition of DMF and ammonia was substituted by aromatic nucleophilic substitution.

In 1982, a chemical technology company in The United States used the mixed system of NaH and DMF in a pilot scale condensation reaction experiment. The reaction temperature was kept at 50 ℃ at the beginning, but then the system spontaneously heated up to 75 ℃, and the use of condensation cycle equipment did not help, resulting in an explosion. They found in their caloretic study that spontaneous warming occurred when NaH was mixed with DMF and DMAc at 26 ℃, and the reaction temperature rapidly rose to 80 ℃, which had exceeded the cooling capacity of the pilot reaction device. Researchers at The Burdick & Jackson Laboratory in the United States also found this problem, and the spontaneous warming phenomenon occurred in many experiments, which is not accidental.

After the occurrence of several explosion accidents of NaH mixing with such solvents, the Organic Process Research & Development journal under the American Chemical Society (ACS) published two editorials emphasizing this problem. However, due to the wide application of this reaction system, Played down the importance of the danger. Articles presenting NaH/DMF rank first in peer-reviewed journals every year.

Articles presenting NaH/DMF rank first in peer-reviewed journals every year

Potential safety risks of DMF when halides exist

The interaction of DMF with chlorinated agents such as thionyl chloride (SOCl2), oxaloyl chloride, cyanouryl chloride, neopentyl chloride and phosphorus chloride oxide (POCl3) has been widely used in organic synthesis. The key intermediates, the Vilsmeier-Haack reagent, are formed by treating DMF with these chlorinated reagents, which then react with alcohols, carboxylic acids, and electron-rich aromatics to form alkyl chloride, acyl chloride, formyl chloride, and nitriles. In these transformations, only catalytic amounts of DMF are required to chlorinate alcohols and carboxylic acids, resulting in the corresponding alkyl chloride and acyl chloride

Vilsmeier-HaackFormation and application of reagents.

In 1977, Spitulnik of Eastman Kodak reported a runaway incident involving DMF/SOCl2 mixtures in a newsletter with Chemical & Engineering News: A total of 82.5 kg of SOCl2 was slowly added to 135kg of DMF at a temperature below 30 ° c during addition and the material was stored overnight at ambient temperature for use the next day. During storage, the mixture exothermically decomposes and releases gases, causing the pressure plate on the reactor to rupture. Root cause investigations showed that SOCl2 contained about 90 PPM of iron and 90 PPM of zinc. Small experiments showed that the SOCl2 / DMF mixture containing 200 PPM iron powder decomposed after 22 hours of agitation at room temperature, while control experiments using freshly distilled SOCl2 showed that the mixture was stable at 60 ℃ for at least 48 h. These results indicate that the presence of trace iron catalyzes the decomposition of SOCl2 /DMF mixture.

Joshi reported a similar incident with SOCl2/DMF in 1986, in which the 400 L reactor experienced a sudden heat release and pressure rise during vacuum distillation of the SOCl2/DMF mixture to remove SO2. A later communication with Chemical & Engineering News by Zemlicka showed that using phosgene (COCl2) instead of SOCl2 could avoid the inherent safety risks associated with SOCl2 /DMF mixtures. Other halogens, such as acyl halides and trichloroisocyanuric acid, alkyl halides (i.e., carbon tetrachloride) and 1,2,3,4,5, 6-hexachlorocyclohexane, and cesium fluoride sulfate (CsSO4F), have also been reported to react very exothermic with DMF, and under certain conditions may be sufficiently intense to lead to uncontrolled or even explosive reactions.