N,N-ジメチルホルムアミド

外観

無色澄明の液体ハーゼン10以下

溶解性

水及びエタノールに極めて溶けやすい。

解説

C3H7NO(73.10)．(CH3)2NCHO．N,N-ジメチルホルムアミドは，略称DMF．代表的な極性有機溶媒の一つ．工業的には，メタノールとアンモニアとの反応で生成するジメチルアミンに，ナトリウムメチラート触媒を加え，加圧下で一酸化炭素と反応させて製造される．融点－61 ℃，沸点153.0 ℃．引火点67 ℃．d²⁵₄0.9445．n²⁵_D1.4269．有機合成では極性化合物の溶媒として広く用いられるほか，芳香族化合物の核ホルミル化，その他，活性水素のホルミル置換の試薬として使用される．ガスクロマトグラフィーではガス状炭化水素分析用の固定相液体として有効である．また，ポリアクリロニトリルの良溶媒で，アクリル系合成繊維ではこれを紡糸溶剤に用いているものが多い．石油化学工業では，ナフサ分解で副生する C4 留分中のブタジエン，C5 留分中のイソプレンの抽出溶剤に用いられ，日本ゼオン社が開発したDMFによる抽出蒸留法(GPB法，GPI法)が工業的に実施されている．森北出版「化学辞典（第2版）

用途

溶媒、試薬、触媒、選択吸収剤

用途

有機合成原料、溶剤、ガス吸収剤、触媒。

用途

ペプチド固相合成の際の保護アミノ酸の溶解や洗浄用。

用途

液体クロマトグラフ分析用溶離液及び溶離液調製用。フェノール樹脂、ポリアミド、尿素樹脂等高分子化合物のHPLC分析。

用途

合成皮革製造溶媒,電子工業用洗浄剤,ブタジエン抽出溶媒,有機合成反応溶媒

用途

用途及び個人専用試薬等。

用途

汎用試薬、溶剤。

用途

紫外、可視及び蛍光スペクトル分析。

使用上の注意

不活性ガス封入

化学的特性

N,N-Dimethylformamide is a colorless or slightly yellow liquid with a boiling point of 153°C and a vapor pressure of 380 Pa at 20°C. It is freely soluble in water and soluble in alcohols, acetone and benzene. N,N-Dimethylformamide is used as solvent, catalyst and gas absorbent. React violently with concentrated sulfuric acid, fuming nitric acid and can even explode. Pure Dimethylformamide is odorless, but industrial grade or modified Dimethylformamide has a fishy smell because it contains impurities of Dimethylamine. Dimethylformamide is unstable (especially at high temperatures) in the presence of a strong base such as sodium hydroxide or a strong acid such as hydrochloric acid or sulfuric acid, and is hydrolyzed to formic acid and dimethylamine.

N,N-Dimethylformamide structure

物理的性質

Clear, colorless to light yellow, hygroscopic, mobile liquid with a faint, characteristic, ammonialike odor. An experimentally determined odor threshold concentration of 100 ppm_v was reported by Leonardos et al. (1969).

使用

N,N-Dimethylformamide (DMF) is a clear liquid that has been widely used in industries as a solvent, an additive, or an intermediate because of its extensive miscibility with water and most common organic solvents. Dimethylformamide solutions are used toprocess polymer fibers, films, and surface coatings; to permit easy spinning of acrylic fibers; to produce wire enamels, and as a crystallization medium in the pharmaceutical industry.
DMF can also be used for formylation with alkyllithium or Grignard reagents. It is used as a reagent in Bouveault aldehyde synthesis and also in Vilsmeier-Haack reaction. It acts as a catalyst in the synthesis of acyl chlorides. It is used for separating and refining crude from olefin gas. DMF along with methylene chloride acts as a remover of varnish or lacquers. It is also used in the manufacture of adhesives, fibers and films.

主な応用

The principal applications of N,N-dimethylformamide are as a solvent and as an extractant, particularly for salts and compounds with high molecular mass. This role is consistent with its interesting combination of physical and chemical properties: low molecular mass, high dielectric constant, electron-donor characteristics, and ability to form complexes. The use of DMF as a component in synthesis is of relatively minor significance, at least commercially. N,N-Dimethylformamide (anhydrous) has been used as solvent for the synthesis of cytotoxic luteinizing hormone-releasing hormone (LH-RH) conjugate AN-152 (a chemotherapeutic drug) and fluorophore C625 [4-(N,N-diphenylamino)-4′-(6-O-hemiglutarate)hexylsulfinyl stilbene]. It may be employed as solvent medium for the various organic reduction reactions.

調製方法

Industrial production of N,N-Dimethylformamide (DMF) is via three separate processes (Eberling 1980). Dimethylamine in methanol is reacted with carbon monoxide in the presence of sodium methoxide or metal carbonyls at 110-150°C and high pressure. Alternately, methyl formate is produced from carbon monoxide and methanol under high pressure at 60-100°C in the presence of sodium methoxide. The resulting methyl formate is distilled and then reacted with dimethylamine at 80-100°C and low pressure. The third process involves reaction of carbon dioxide, hydrogen and dimethylamine in the presence of halogen-containing transition metal compounds to yield DMF.

定義

ChEBI: N,N-dimethylformamide is a member of the class of formamides that is formamide in which the amino hydrogens are replaced by methyl groups. It has a role as a polar aprotic solvent, a hepatotoxic agent and a geroprotector. It is a volatile organic compound and a member of formamides. It is functionally related to a formamide.

製造方法

Two processes are used commercially to produce dimethylformamide. In the direct or one-step process, dimethylamine and carbon monoxide react at 100°C and 200 psia in the presence of a sodium methoxide catalyst to make dimethylformamide. The homogenous catalyst is separated from the crude DMF, which is then refined to the final product. In the indirect process, methyl formate is isolated, and then reacted with dimethylamine to form DMF. To obtain methyl formate, two methods may be used - dehydrogenation of methanol and esterification of formic acid.
The two-step process for the synthesis of N,N-dimethylformamide differs from direct synthesis because methyl formate is prepared separately and introduced in the form of ca. 96% pure (commercialgrade) material. Equimolar amounts of methyl formate and N,N-dimethylamine are subjected to a continuous reaction at 60-100°C and 0.1 – 0.3 MPa. The resulting product is a mixture of N,N-dimethylformamide and methanol. The purification process involves distillation and is analogous to that described for direct synthesis. However, no separation of salts is required because no catalysts are involved in the process. According to the corrosive properties of both starting materials and products, stainless steel has to be used as material of construction for production facilities.

一般的な説明

A water-white liquid with a faint fishy odor. Flash point 136°F. Slightly less dense than water. Vapors heavier than air. Toxic by inhalation or skin absorption. May irritate eyes.

空気と水の反応

Flammable. Water soluble.

反応プロフィール

N,N-Dimethylformamide may react violently with a broad range of chemicals, e.g.: alkaline metals (sodium, potassium), azides, hydrides (sodium borohydride, lithium aluminum hydride), bromine, chlorine, carbon tetrachloride, hexachlorocyclohexane, phosphorus pentaoxide, triethylaluminum, magnesium nitrate, organic nitrates. Forms explosive mixtures with lithium azide [Bretherick, 5th ed., 1995, p. 453]. Oxidation by chromium trioxide or potassium permanganate may lead to explosion [Pal B. C. et al., Chem. Eng. News, 1981, 59, p. 47].

健康ハザード

The acute toxicity of DMF is low by inhalation, ingestion, and skin contact. Contact with liquid DMF may cause eye and skin irritation. DMF is an excellent solvent for many toxic materials that are not ordinarily absorbed and can increase the hazard of these substances by skin contact. Exposure to high concentrations of DMF may lead to liver damage and other systemic effects. Dimethylformamide is listed by IARC in Group 2B ("possible human carcinogen"). It is not classified as a "select carcinogen" according to the criteria of the OSHA Laboratory Standard. No significant reproductive effects have been observed in animal tests. Repeated exposure to DMF may result in damage to the liver, kidneys, and cardiovascular system

燃焼性と爆発性

DMF is a combustible liquid (NFPA rating = 2). Vapors are heavier than air and may travel to source of ignition and flash back. DMF vapor forms explosive mixtures with air at concentrations of 2.2 to 15.2% (by volume). Carbon dioxide or dry chemical extinguishers should be used to fight DMF fires.

工業用途

World production capacity of DMF is about 225 x 10³ tons per year. The main application of DMF is as solvent in industrial processes, especially for polar polymers such as Polyvinylchloride, polyacrylonitrile and polyurethanes. DMF solutions of high molecular weight polymers are processed to fibers, films, surface coatings and synthetic leathers. Since salts can be dissolved and dissociated in DMF, the solutions are used in electrolytic capacitors and certain electrolytic processes (Eberling 1980).

接触アレルゲン

This is an organic solvent for vinyl resins and acetylene, butadiene, and acid gases. It caused contact dermatitis in a technician at an epoxy resin factory and can provoke alcohol-induced flushing in exposed subjects.

発がん性

DMF is not carcinogenic to animals except under very high inhalation exposure conditions. No increase in tumors was seen in rats that inhaled 25, 100, or 400 ppm for 6 h/day, 5 days/week for 2 years. Similarly, no tumors were produced in mice under the same conditions for 18 months. In that chronic experiment, rats and mice were exposed by inhalation (6 h/day, 5 days/week) to 0, 25, 100, or 400 ppm DMF for 18 months (mice) or 2 years (rats). Body weights of rats exposed to 100 (males only) and 400 ppm were reduced and, conversely, body weights were increased in 400 ppm mice. Serum sorbitol dehydrogenase activity was increased in rats exposed to 100 or 400 ppm. DMF-related morphological changes in rats were observed only in the liver and consisted of increased relative liver weights, centrilobular hepatocellular hypertrophy, lipofuscin/hemosiderin accumulation in Kupffer cells, and centrilobular single cell necrosis (400 ppm only). The same liver effects were seen in all groups of mice, although the response at 25 ppm was judged as minimal.

環境運命予測

Biological. Incubation of [¹⁴C]N,N-dimethylformamide (0.1–100 μg/L) in natural seawater resulted in the compound mineralizing to carbon dioxide. The rate of carbon dioxide formation was inversely proportional to the initial concentration (Ursin, 1985).
Chemical. Reacts with acids or bases forming formic acid and dimethylamine (BASF, 1999)

代謝経路

Three urinary metabolites are identified in humans and rodents, and the metabolites quantified are N- (hydroxymethyl)-N-methylformamide (HMMF), resulting in N-methylformamide (NMF) and N-acetyl-S-(N- methylcarbamoyl)cysteine (AMCC). Ten volunteers who absorb between 28 and 60 mmol/kg DMF during an 8 h exposure to DMF in air at 6 mg=m3 excrete in the urine within 72 h between 16.1 and 48.7% of the dose as HMMF, between 8.3 and 23.9% as formamide, and between 9.7 and 22.8% as AMCC. AMCC together with HMMF is also detected in the urine of workers after occupational exposure to DMF. There is a quantitative difference between the metabolic pathway of DMF to AMCC in humans and rodents.

貯蔵

DMF should be used only in areas free of ignition sources, and quantities greater than 1 liter should be stored in tightly sealed metal containers in areas separate from oxidizers.

不和合性

Though stable at normal temperatures and storage conditions, DMF may react violently with halogens, acyl halides, strong oxidizers, and polyhalogenated compounds in the presence of iron. Decomposition products include toxic gases and vapors such as dimethylamine and carbon monoxide. DMF will attack some forms of plastics, rubber, and coatings.

廃棄物の処理

Excess DMF and waste material containing this substance should be placed in an appropriate container, clearly labeled, and handled according to your institution's waste disposal guidelines.