75-12-7 Usage
Chemical Description
Formamide is used as a solvent in the condensation reaction to form bicyclic 41.
Description
Formamide, also known as methanamide, is the simplest monocarboxylic acid amide, obtained by formal condensation of formic acid with ammonia. It is a colorless, viscous liquid with a faint odor of ammonia and has hygroscopic properties. Formamide is denser than water, with a freezing point of 36°F, a relative molecular mass of 45.04, and a boiling point of 210.5°C. It is insoluble in ether and chlorinated solvents, slightly soluble in benzene, and miscible with water, methanol, ethanol, acetic acid, acetone, dioxane, ethylene glycol, phenol, and low-grade esters. Formamide contains two active functional groups, the carbonyl and amide groups, making it highly reactive and capable of undergoing various chemical reactions.
Uses
1. Organic Synthesis:
Formamide is used as a raw material for synthesizing various compounds, including imidazole, pyrimidine, 1,3,5-triazine, caffeine, theophylline, and theobromine. It is also used in the production of dyes, spices, paints, adhesives, and textile and paper treatment agents.
2. Solvent:
Formamide serves as an excellent organic solvent due to its high dielectric constant. It is mainly applied to the spinning of acrylonitrile copolymers, ion exchange resins, and plastics antistatic or conductive coatings. It is also used as a solvent in the chemical industry, for paper processing agents, and as a softening agent in the fiber industry and animal glue.
3. Analytical Reagent:
Formamide is used as an analytical reagent for measuring the amino acid content of rice and in hybridization protocols requiring lower hybridization temperatures.
4. Agricultural Applications:
Formamide is used in the production of liquid fertilizers for foliar application of nitrogen. A mixture of formamide, urea, and ammonium nitrate is used as a solution fertilizer with a salt-out temperature of 0°C and contains more than 35% nitrogen.
5. Pharmaceutical Industry:
In the field of organic synthesis, formamide has the most applications in medicine, as well as in other fields such as pesticides, dyes, pigments, fragrances, and additives.
6. Industrial Applications:
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.
7. Softening Agent:
Formamide can be used as a softener and solvent for animal glue and paper.
8. Chemical Reactions:
Formamide can undergo various chemical reactions, such as dehydration, CO removal, the introduction of an amino group, an acyl group, and cyclization reactions. It can also form complexes with cobalt, copper, and nickel salts.
9. Separation and Purification:
Formamide can be used for separating chlorosilane and purifying grease.
Acute toxicity
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.
Acute toxicity
Oral-rat LD50: 5577 mg/kg; Oral-Mouse LD50: 3150 mg/kg.
Production method
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.
Toxicity grading
Poisoning
Irritation data
Eye-rabbit 100 mg severe.
Flammability and hazardous characteristics
Flammable with fire releasing toxic nitric oxide gas.
Storage properties
Warehouse: cold, ventilation, dry.
Extinguishing Media
Carbon dioxide, dry chemical powder.
Professional standards
TWA 15 mg/m3; STEL 45 mg/m3
Production Methods
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.
Air & Water Reactions
Hygroscopic. Water soluble.
Reactivity Profile
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 .
Hazard
Toxic material. Toxic by skin absorption.
Health Hazard
INHALATION: A moderate irritant to mucous membranes. EYES: Moderately irritating to the eyes. SKIN: A mild to moderate irritant to the skin.
Health Hazard
Formamide is moderately irritating to the skin and mucous membranes (Windholz 1983).
Safety Profile
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.
Potential Exposure
Formamide is a powerful solvent. It is
also used as an intermediate in pharmaceutical
manufacture.
Environmental Fate
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.
Metabolism
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.
Shipping
UN2810 Toxic solids, organic, n.o.s., Hazard
Class: 6.1; Labels: 6.1-Poisonous materials, Technical
Name Required.
Purification Methods
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.]
Toxicity evaluation
The mechanism of toxicity of formamide is not known; the
response profile is quite different from the better studied
dimethyl derivative.
Incompatibilities
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).
Waste Disposal
Dissolve in a combustible
solvent and dispose by burning in a furnace equipped with
an alkali scrubber for the exit gases.
Check Digit Verification of cas no
The CAS Registry Mumber 75-12-7 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 7 and 5 respectively; the second part has 2 digits, 1 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 75-12:
(4*7)+(3*5)+(2*1)+(1*2)=47
47 % 10 = 7
So 75-12-7 is a valid CAS Registry Number.
InChI:InChI=1/CH3NO/c2-1-3/h1H,(H2,2,3)
75-12-7Relevant articles and documents
Isomerization of matrix-isolated formamide: IR-spectroscopic detection of formimidic acid
Maier, Guenther,Endres, Joerg
, p. 1061 - 1063 (2007/10/03)
Ultraviolet irradiation of matrix-isolated formamide (1) in solid argon with light of wavelength 248 nm leads to the formation of formimidic acid (2). Comparison of the experimental IR spectrum of the photoproduct with the calculated IR spectrum of 2 shows clearly that two rotamers 2a and 2b are formed.
