Formamide

It is colorless, odorless and oily liquid with slight ammonia-odor when containing impurities. It has hygroscopicity property. It has a relative molecular mass of 45.04. It has the relative density being 1.1334, the melting point being 2.55 ℃, the boiling point being 210.5 ℃, the refractive index being 1.4475, the flash point being 154 ℃ and the viscosity being 3.76mPa • s (20 ℃). It is insoluble in ether and chlorinated solvents, slightly soluble in benzene and is miscible with water, methanol, ethanol, acetic acid, acetone, dioxane, ethylene glycol, phenol and low grade ester. This product can dissolve the casein but does not dissolve albumin. This product can dissolve casein, dextrose, corn protein, gelatin, glue, resin, starch, lignin, cellulose acetate, nylon, and some inorganic salts: the chloride compounds of copper, lead, zinc, tin, cobalt, iron, aluminum and nickel and also some kinds of sulfates and nitrates. At room temperature, formamide has a low hydrolysis rate. Raising the temperature or the addition of acid, alkali can all accelerate the hydrolysis rate. In the presence of a catalyst, being heated to less than 35 ℃ can decompose and release hydrogen cyanide. Formamide contains two active functional groups, namely the carbonyl and amide groups. It is easy to have chemical reaction to produce a lot of nitrogen-containing heterocyclic compound. Formamide can also react with a mineral acid to generate formic acid and ammonium salt. In the presence of a catalyst, it can react with organic halide or alcohol to form formic esters. This product can also react with β-diketone, β-imino ketone, aliphatic acyloin, arene acyloin as well as heterocyclic acyloin. It can also form complex with cobalt, copper and nickel salts. Formamide, in case of strong dehydrating agent such as phosphorus pentoxide, it can generate hydrogen cyanide. It can react with phosphorus pentasulfide to generate sulfur formamide. Formamide has strong corrosion effect on copper, brass, lead and rubber, therefore the storage and transportation should be paid attention.
The main purposes: formamide can be used as the softener and solvent of animal glue and paper. It can also be used as the solvent of the spinning of the acrylonitrile copolymer, the polymerization of unsaturated amine polymerization and the production of pharmaceuticals as well as the solvent for extraction of grease and the dissolving items mentioned above. As intermediates, it can be applied the synthesis of imidazole, pyrimidine, 1, 3, 5-triazine, caffeine, theophylline and theobromine. Furthermore, it can also be used as the raw material of making dyes, spices, paints, adhesives, textile and paper treatment agent as well as the production of formic acid, dimethyl formamide and so on.
The above information is edited by the chemicalbook of Dai Xiongfeng.

The LD50 for rat via stomach is 6.1g/kg and for mice is 3.15g/kg. Acute symptoms is characterized by the injury of the nervous system, accompanied with conjunctivitis and respiratory disorders, straight convulsions and the final death after 3 to 4 days. The threshold concentration for chronic inhalation effects was 6 ± 4mg/m3. For the maximum allowable concentration for operating environment: for United States, the value is 30 mg/m3 (20 ppm) while the value is 3 mg/m3 (vapor, absorbed through the skin) for Soviet Union.

It is transparent oily liquid with slight ammonia smell. It has hygroscopic property. It is miscible with water and ethanol, slightly soluble in benzene, chloroform and ether.

It can be used as the raw material for synthesizing imidazole, pyrimidine, 1, 3, 5-triazine, caffeine as well as the solvents for making spinning of acrylonitrile copolymer and plastic anti-static coating, etc.
Formamide has active reactive and special dissolving capability. It can be used as the raw material for organic synthesis, paper processing agents, softening agent of fiber industry and animal glue as well as being used as the analytical reagent for measuring the amino acid content of rice. In the field of organic synthesis, it has most application in medicine as well as a lot of applications in other fields such as pesticides, dyes, pigments, fragrances and additives. It is also a kind of excellent organic solvent and is mainly applied to the spinning of acrylonitrile copolymers and ion exchange resins and plastics antistatic coating or conductive coating. In addition, it can also be used for separating chlorosilane and purifying grease. Formamide can have various kinds of reactions, in addition to have its three hydrogen atoms participate in the reaction, can also be subject to dehydration, CO removal, the introduction of an amino group, an acyl group and cyclization reaction. Take cyclization as an example, diethyl malonate can have cyclization reaction with formamide to generate the intermediate of vitamin B4, the 4, 6-dihydroxypyrimidine. O-aminobenzoic acid can have cyclization reaction with formamide to generate the quinazolinone-4 which is the intermediate for the synthesis of antiarrhythmic drug phenantrolihne. 3--amino-4-ethoxycarbonyl-pyrazole can have cyclization reaction with formamide to generate the inhibitor of the xanthine oxidase, allopurinol. EDTA can have cyclization reaction with formamide to give anti-cancer drugs ethylenediamine. Methyl ethyl methoxymalonate can have cyclization reaction with formamide to generate the intermediate of sulfonamide drug, 5-methoxy-4, 6-dihydroxy pyrimidine disodium.
It can be used as analytical reagents, solvents and softening agents as well as being used in organic synthesis.
It can be applied to medicine and pesticide industry.

1. One-Step method: the first step is through the reaction of carbon monoxide and methanol for generating methyl formate in the presence of sodium methoxide. The second step: the methyl formate is further subject to aminolysis for generation of formamide with the reaction conditions being 80-100 ℃ and 0.2-0.6 MPa. This method has relative problems. 2. The method of formic acid; the formic acid first has esterification reaction with methanol to generate methyl formate which undergoes aminolysis to generate formamide with the separation of methanol and impurities through distillation to obtain the final product. Owing to its high cost, this method has been gradually eliminated. 3. One Step method: this is via the reaction of carbon monoxide and ammonia for the direct synthesis of formamide in high pressure (10-30 MPa) and a temperature of 80-100 ℃ with the sodium methylate as the catalyst. 4. The formic acid and urea method. 5. The new method has sodium and ammonium salts for reaction to generate formamide at a certain temperature and pressure. This method has already applied domestic invention patent.

Toxic substances.

Poisoning

Oral-rat LD50: 5577 mg/kg; Oral-Mouse LD50: 3150 mg/kg.

Eye-rabbit 100 mg severe.

Flammable with fire releasing toxic nitric oxide gas.

Warehouse: cold, ventilation, dry.

Carbon dioxide, dry chemical powder.

TWA 15 mg/m³; STEL 45 mg/m3

Formamide is a colorless, viscous liquid with afaint ammonia odor. Molecular weight=45.05; Specificgravity (H2O:1)=1.13; Boiling point=(decomposes)210.5℃; Freezing/Melting point=2.5℃; Vapor pressure 50.1 mmHg at 30℃; Flash point=154℃. Autoignitiontemperature ≥500℃. Hazard Identification (based onNFPA-704 M Rating System): Health 2, Flammability 1,Reactivity 0. Good solubility in water.

Clear, colorless liquid

Formamide is hydrolyzed very slowly at room temperature. Acids, bases and elevated temperatures accelerate the hydrolysis (Eberling 1980).

Formamide is a colorless, viscous liquid. Faint ammonia-like odor.

Formamide is a good solvent for proteins and salts owing to its high dielectric constant. Its main applications are as a solvent in the chemical industry, as a softener for paper, as an intermediate for the manufacturing of formic acid and esters and hydrocyanic acid, and as a reaction medium.

Formamide destabilizes nucleic acid duplexes and may be used, typically, at a concentration of 50%, in hybridization protocols requiring lower hybridization temperatures.

As ionizing solvent, manufacture of formic esters, hydrocyanic acid by catalytic dehydration, as softener for paper, animal glues, water-sol gums.

ChEBI: The simplest monocarboxylic acid amide, obtained by formal condensation of formic acid with ammonia. The parent of the class of formaldehydes.

Formamide is produced commercially by two processes (Eberling 1980). In a direct synthesis, ammonia and carbon monoxide react at 100-300 atm and 80-100°C in methanolic sodium methoxide. In the second, a two-stage synthesis, carbon monoxide and methanol form methylformate in the presence of sodium methoxide. The methylformate is treated with liquid or gaseous ammonia at 2-6 atm and 80-100°C.

A colorless liquid with a faint odor of ammonia. Denser than water. Freezing point 36°F.

Hygroscopic. Water soluble.

Formamide is incompatible with strong oxidizers, acids and bases. Sensitive to light. Reacts with water very slowly at room temperature, but rate is accelerated by acids and bases at elevated temperatures. Incompatible with iodine, pyridine and sulfur trioxide. Reacts explosively with furfuryl alcohol, H2O2, Tl(NO3)3.H2O, nitromethane and P2O5. An effective solvent: dissolves casein, glucose, tannins, starch, lignin, polyvinyl alcohol, cellulose acetate, nylon, the chlorides of copper, lead, zinc, tin, cobalt, iron, aluminum and nickel, the acetates of the alkali metals, some inorganic sulfates and nitrates. Attacks copper and brass .

Toxic material. Toxic by skin absorption.

INHALATION: A moderate irritant to mucous membranes. EYES: Moderately irritating to the eyes. SKIN: A mild to moderate irritant to the skin.

Formamide is moderately irritating to the skin and mucous membranes (Windholz 1983).

Fonnamide is an organic compound containing the amide group -CONH₂. It is made from formic acid or its ester with ammonia. It is also made from ammonia and carbon monoxide.
Formamide is used in making liquid fertilizers for foliar application of nitrogen. For example, a mixture of formamide, urea and ammonium nitrate is used as a solution fertilizer and has a salt-out temperature of 0°C. It contains more than 35% nitrogen, unlike the aqueous formulations of urea, and ammonium nitrate, which have 32 % nitrogen.Formamide is a good solvent for many organic compounds.

Formamide is used in the large scale production of formic acid by reaction with inorganic acids, as an intermediate in the chemical industry, as a solvent in the processing of plastics, and as a solvent in felt-tip pens (Eberling 1980).

Poison by skin contact and subcutaneous routes. Moderately toxic by ingestion, intraperitoneal, and intramuscular routes. An irritant to skin, eyes, and mucous membranes. Experimental teratogenic and reproductive effects. An eye irritant. Mutation data reported. Combustible when exposed to heat or flame; can react vigorously with oxidizing materials. Incompatible with 12, pyridine,SO3. When heated to decomposition it emits toxic fumes of NOx. Has exploded while in storage.

Formamide is a powerful solvent. It is also used as an intermediate in pharmaceutical manufacture.

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 CPR ifheart action has stopped. Transfer promptly to a medicalfacility. When this chemical has been swallowed, get medical attention. Give large quantities of water and inducevomiting. Do not make an unconscious person vomit.

If released to air, formamide will exist solely as a vapor in the ambient atmosphere. Vapor-phase formamide will be degraded in the atmosphere by reaction with photochemically produced hydroxyl radicals. The half-life for this reaction in air is estimated to be 8.0 days. If released to soil, formamide is expected to have very high mobility. Volatilization from moist soil surfaces is not expected to be an important fate process. If released into water, formamide is not expected to adsorb to suspended solids and sediment. Several biodegradation screening studies have observed significant biodegradation of formamide, which suggests that biodegradation may be important. Volatilization from water surfaces is not expected to be an important fate process based upon this compound’s estimated Henry’s law constant.

There are only very few reports on the metabolic fate of formamide in the literature. Halsey (1898) found that formamide gave rise to as much urinary formate in the dog as did formic acid, and assumed complete hydrolysis of the amide in vivo. In a study by Bray et al (1949) the hypothesis was tested that formamide undergoes metabolic hydrolysis in rabbits. Acidic substances were titrated after extraction by ether, before and after hydrolysis of urine samples. The ether-soluble acid determined in hydrolyzed urine was assumed to reflect the amount of formamide excreted unchanged. The difference between the amount of amide administered and the total amount excreted unchanged was considered to represent amide which was metabolically hydrolyzed. After administration of 2-4 g per rabbit orally, 39% of the dose was recovered unchanged using this method. When formamide was incubated with rabbit liver extracts or liver slices, only very little hydrolysis was detected by this method.

Color Code—Green: General storage may be used.Prior to working with this chemical you should be trainedon its proper handling and storage. Store in tightly closedcontainers in a cool, well-ventilated area away from moisture and other incompatible materials listed above. Wherepossible, automatically pump liquid from drums or otherstorage containers to process containers.

UN2810 Toxic solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required.

Formamide is easily hydrolysed by acids and bases. It also reacts with peroxides, acid halides, acid anhydrides, esters and (on heating) alcohols, while strong dehydrating agents convert it to a nitrile. It is very hygroscopic. Commercial material often contains acids and ammonium formate. Vorhoek [J Am Chem Soc 58 2577 1956] added some bromothymol blue to formamide and then neutralised it with NaOH before heating to 80-90o under reduced pressure to distil off ammonia and water. The amide is again neutralised and the process is repeated until the liquid remained neutral on heating. Sodium formate is added, and the formamide is concentrated under reduced pressure at 80-90o. The distillate is again neutralised and redistilled. It is then fractionally crystallised in the absence of CO2 and water by partial freezing. Formamide (specific conductance 2 x 10-7 ohm-1 cm-1) of low water content is dried by passage through a column of 3A molecular sieves, then deionized by treatment with a mixed-bed ion-exchange resin loaded with H+ and HCONH-ions (using sodium formamide in formamide)[Notley & Spiro J Chem Soc (B) 362 1966]. [Beilstein 2 IV 45.]

The mechanism of toxicity of formamide is not known; the response profile is quite different from the better studied dimethyl derivative.

Forms hydrocyanic acid with water solutions. Hygroscopic (absorbs moisture from air). Incompatible with nonoxidizing mineral acids; strong acids; ammonia, cresols, iodine, isocyanates, oleum, phenols, pyr idine, sulfur trioxide; oxidizers, iodine, pyridine. Formamide decomposes on heating @ 180℃ forming ammonia, water, carbon monoxide and hydrogen cyanide. Attacks metals, such as aluminum, iron, copper, brass, lead, and natural rubber. Thermal decomposition may release deadly hydrogen cyanide. Compounds of the carboxyl group react with all bases, both inorganic and organic (i.e., amines) releasing substantial heat, water and a salt that may be harmful. Incompatible with arsenic compounds (releases hydrogen cyanide gas), diazo compounds, dithio carbamates, isocyanates, mercaptans, nitrides, and sulfides (releasing heat, toxic and possibly flammable gases), thiosulfates and dithionites (releasing hydrogen sulfate and oxides of sulfur).

Dissolve in a combustible solvent and dispose by burning in a furnace equipped with an alkali scrubber for the exit gases.