| Identification | More | [Name]
Azabenzene | [CAS]
110-86-1 | [Synonyms]
1-propen-3-ol
2-Propen-1-c
2-PROPEN-1-OL
2-PROPENE-1-OL
2-PROPENOL
3-hydroxypropene
AA
AKOS BBS-00004376
ALLYL ALCOHOL
ALLYL ALCOHOL, POLYMER-BOUND
azabenzene
FEMA 2932
FEMA 2966
FEMA NUMBER 2966
PY
PYR
PYRIDINE
PYRIDINE FRACTION
ai3-01240
Azine | [EINECS(EC#)]
203-809-9 | [Molecular Formula]
C3H6O | [MDL Number]
MFCD00002920 | [Molecular Weight]
58.08 | [MOL File]
110-86-1.mol |
| Chemical Properties | Back Directory | [Appearance]
Pyridine is a colorless liquid. Nauseating,
sickening fish-like odor. The Odor Threshold is 0.17 ppm. | [Melting point ]
-42 °C | [Boiling point ]
96-98 °C(lit.)
| [density ]
0.983 g/mL at 20 °C
| [vapor density ]
2.72 (vs air)
| [vapor pressure ]
23.8 mm Hg ( 25 °C)
| [FEMA ]
2966 | [refractive index ]
n20/D 1.509(lit.)
| [Fp ]
68 °F
| [storage temp. ]
Store at RT. | [solubility ]
H2O: in accordance | [form ]
Liquid | [pka]
5.25(at 25℃) | [color ]
colorless | [Odor]
Nauseating odor detectable at 0.23 to 1.9 ppm (mean = 0.66 ppm) | [PH]
8.81 (H2O, 20℃) | [Relative polarity]
0.302 | [Stability:]
Stable. Flammable. Incompatible with strong oxidizing agents, strong acids. | [explosive limit]
12.4% | [Odor Threshold]
0.063ppm | [Odor Type]
fishy | [Water Solubility ]
Miscible | [FreezingPoint ]
-42℃ | [λmax]
λ: 305 nm Amax: 1.00
λ: 315 nm Amax: 0.15
λ: 335 nm Amax: 0.02
λ: 350-400 nm Amax: 0.01 | [Merck ]
14,7970 | [BRN ]
103233 | [Henry's Law Constant]
18.4 at 30 °C (headspace-GC, Chaintreau et al., 1995) | [Dielectric constant]
12.5（20℃） | [Exposure limits]
TLV-TWA 5 ppm (～15 mg/m3) (ACGIH,
MSHA,and OSHA); STEL 10 ppm (ACGIH),
IDLH 3600 ppm (NIOSH). | [Contact allergens]
Pyridine (110-86-1) and its derivative
(substituted pyridines) are widely used in chemistry.
Pyridine is a solvent used for many organic compounds
and anhydrous metallic salt chemicals. Contained in
Karl Fischer reagent, it induced contact dermatitis in a
laboratory technician. No cross-sensitivity is observed
between those different substances.
| [InChIKey]
JUJWROOIHBZHMG-UHFFFAOYSA-N | [LogP]
0.64 at 20℃ | [CAS DataBase Reference]
110-86-1(CAS DataBase Reference) | [IARC]
2B (Vol. 77, 119) 2019 | [NIST Chemistry Reference]
Pyridine(110-86-1) | [EPA Substance Registry System]
110-86-1(EPA Substance) |
| Hazard Information | Back Directory | [Definition]
ChEBI: An azaarene comprising a benzene core in which one -CH group is replaced by a nitrogen atom. It is the parent compound of the class pyridines. | [General Description]
A clear colorless to light yellow liquid with a penetrating nauseating odor. Density 0.978 g/cm3. Flash point 68°F. Vapors are heavier than air. Toxic by ingestion and inhalation. Combustion produces toxic oxides of nitrogen. | [Reactivity Profile]
PYRIDINE(110-86-1) is a base. Reacts exothermically with acids. During preparation of a complex of PYRIDINE(110-86-1) with chromium trioxide, an acid, the proportion of chromium trioxide was increased. Heating from this acid-base reaction led to an explosion and fire [MCA Case History 1284 1967]. A 0.1% solution of PYRIDINE(110-86-1) (or other tertiary amine) in maleic anhydride at 185°C gives an exothermic decomposition with rapid evolution of gas [Chem Eng. News 42(8); 41 1964]. Mixing PYRIDINE(110-86-1) in equal molar portions with any of the following substances in a closed container caused the temperature and pressure to increase: chlorosulfonic acid, nitric acid (70%), oleum, sulfuric acid (96%), or propiolactone [NFPA 1991]. The combination of iodine, PYRIDINE(110-86-1), sulfur trioxide, and formamide developed a gas over pressurization after several months. This arose from the slow formation of sulfuric acid from external water, or from dehydration of the formamide to hydrogen cyanide. Ethylene oxide and SO2 can react violently in PYRIDINE(110-86-1) solution with pressurization if ethylene oxide is in excess (Nolan, 1983, Case History 51). | [Air & Water Reactions]
Highly flammable. Soluble in water. | [Hazard]
Flammable, dangerous fire risk, explosive
limits in air 1.8–12.4%. Toxic by ingestion and inhalation. Skin irritant, liver and kidney damage.
Questionable carcinogen.
| [Health Hazard]
Vapor irritates eyes and nose. Liquid irritates skin and is absorbed through the skin. Overexposure causes nausea, headache, nervous symptoms, increased urinary frequency. | [Potential Exposure]
Pyridine is used as a solvent in
the chemical industry and as a denaturant for ethyl alco-
hol; as an intermediate in the production of pesticides;
in pharmaceuticals; in the manufacture of paints,
explosives, dyestuffs, rubber, vitamins, sulfa drugs; and
disinfectants. | [Fire Hazard]
Behavior in Fire: Vapor is heavier than air and may travel considerable distance to source of ignition and flash back. | [First aid]
If this chemical gets into the eyes, remove any
contact lenses at once and irrigate immediately for at least
15 minutes, occasionally lifting upper and lower lids. Seek
medical attention immediately. If this chemical contacts the
skin, remove contaminated clothing and wash immediately
with soap and water. Seek medical attention immediately.
If this chemical has been inhaled, remove from exposure,
begin rescue breathing (using universal precautions, includ-
ing resuscitation mask) if breathing has stopped and CPR
if heart action has stopped. Transfer promptly to a medical
facility. When this chemical has been swallowed, get
medical attention. Give large quantities of water and induce
vomiting. Do not make an unconscious person vomit. | [Shipping]
UN1992 Flammable liquids, toxic, n.o.s., Hazard
Class: 3; Labels: 3-Flammable liquid, 6.1-Poisonous mate-
rials, Technical Name Required. | [Incompatibilities]
Violent reaction with strong oxidizers;
strong acids; chlorosulfonic acid; maleic anhydride; oleum
iodine. | [Description]
Pyridine(110-86-1) is a solvent for many organic compounds and
anhydrous metallic salts chemicals. Contained in Karl
Fischer reagent, it induced contact dermatitis in a
laboratory technician.
| [Waste Disposal]
Controlled incineration
whereby nitrogen oxides are removed from the effluent gas
by scrubber, catalytic or thermal devices . | [Physical properties]
Clear, colorless to pale yellow, flammable liquid with a sharp, penetrating, nauseating fish-like
odor. Odor threshold concentrations in water and air were 2 ppm (Buttery et al., 1988) and 21 ppbv
(Leonardos et al., 1969), respectively. Detection odor threshold concentrations of 0.74 mg/m3 (2.3
ppmv) and 6 mg/m3 (1.9 ppmv) were experimentally determined by Katz and Talbert (1930) and
Dravnieks (1974), respectively. Cometto-Mu?iz and Cain (1990) reported an average nasal
pungency threshold concentration of 1,275 ppmv. | [Occurrence]
Pyridine was discovered by Anderson in coal tar in 1846 (Windholz et al 1983). It
is found in tobacco smoke (Vohl and Eulenberg 1871; Lehmann 1909) and roasted
coffee (Bertrand and Weisweiller 1913). Pyridine is found in wood oil and in the
leaves and roots of Atropa belladonna (HSDB 1988), and is also a component of
creosote oil (Krone et al 1986). | [Preparation]
Pyridine is produced either by isolation from natural sources such as coal, or through chemical synthesis (HSDB 1989). Pyridine is produced by the fractional distillation of coal-tar residues (HSDB 1989; NSC 1978; Santodonato et al. 1985) in which 1 ton of coal produces 0.07-0.21 pounds of pyridine bases of which 57% is pyridine (Santodonato et al, 1985). Synthetically produced pyridine is currently the more important source of pyridine for commercial uses (Santodonato et al. 1985). Small amounts of pyridine are synthesized from acetaldehyde, formaldehyde, and ammonia with a fluidized silica-alumina catalyst, followed by fractionation to isolate the pyridine (Harper et al. 1985; HSDB 1989; NSC 1978).
Pyridine is produced from natural sources by Crowley Tar Products of Stow, Ohio, and Oklahoma City, Oklahoma (Harper et al. 1985; HSDB 1989; SRI 1986, 1987, 1988). Pyridine is synthetically produced by two companies, the Nepera Chemical Co. of Harriman, New York and the Reilly Tar and Chemical Corporation of Indianapolis, Indiana (Harper et al. 1985; SRI 1986, 1987, 1988).
| [Production Methods]
Pyridine is produced from the gases obtained by the coking of coal and by direct
synthesis. The light-oil fraction of coal tar is treated with sulfuric acid to produce
water-soluble pyridine salts and then the pyridine bases are recovered from the
aqueous phase by sodium hydroxide or ammonia (Jori et al 1983). The majority of
U.S. production is through synthetic means. This process uses a vapor-phase
reaction of acetaldehyde, formaldehyde and ammonia, which yields a mixture of
pyridine and 3-methylpyridine (Santodonato et al 1985). The product ratio depends
on the relative amounts of acetaldehyde and formaldehyde. Added methanol
increases the yield. The U.S. production of pyridine was estimated at 32 to 47
million pounds in 1975 (Reinhardt and Brittelli 1981). Pyridine is commercially
available in technical, 2° and 1° grades, the latter two referring to their boiling
ranges. Major impurities are higher boiling homologues, such as picolines, lutidines
and collidines, which are mono-, di-, and trimethylpyridines (Santodonato et al
1985; Jori et al 1983). | [Aroma threshold values]
Detection: 0.079 to 790 ppb; recognition: 7.9 to 40 ppm | [Flammability and Explosibility]
Pyridine is a highly flammable liquid (NFPA rating = 3), and its vapor can travel a
considerable distance and "flash back." Pyridine vapor forms explosive mixtures
with air at concentrations of 1.8 to 12.4% (by volume). Carbon dioxide or dry
chemical extinguishers should be used for pyridine fires. | [Industrial uses]
Pyridine(110-86-1) is a good solvent for a large number of compounds, both organic and inorganic (Windholz et al 1983). About 50% of pyridine used in the U.S. is for the production of agricultural chemicals, such as the herbicides paraquat, diquat and triclopyr and the insecticide chlorpyrifos. Other uses are in the production of piperidine; the manufacture of pharmaceuticals, such as steroids, vitamins and antihistamines; and as a solvent. Solvent uses are found in both the pharmaceutical and polycarbonate resin industries. It is particularly useful as a solvent in processes where HC1 is evolved (Santodonato et al 1985). Minor uses for pyridine are for the denaturation of alcohol and antifreeze mixtures, as a dyeing assistant in textiles and as a flavoring agent (Jori et al 1983; Furia 1968; HSDB 1988). | [Carcinogenicity]
Pyridine was not carcinogenic in
several chronic subcutaneous studies.
F344 rats were given pyridine orally in drinking water at
doses of 0, 7, 14, or 33 mg/kg for 2 years. The top dose
produced a decrease in body weights and water consumption.
Increased renal tubular adenoma or carcinoma and tubular
hyperplasia were observed in males at 33 mg/kg. Increased
mononuclear cell leukemia was observed in females at 14
and 33 mg/kg, which was considered equivocal in terms of
the relationship to pyridine exposure, since this is a common
finding in this strain of rat. Concentration-related nonneoplastic
change in the liver was seen at 33 mg/kg. Male
Wistar rats were similarly treated with doses of 0, 8, 17, or
36 mg/kg for 2 years. Decreased survival and body weights
were seen at 17 and 36 mg/kg. Increased testicular cell
adenomas were seen at 36 mg/kg. No changes in survival
or neoplasm rates in other tissues, including the kidney, were
reported although increased nephropathy and hepatic centrilobular
degeneration/necrosis was observed in some pyridine-
treated rats. | [Source]
Pyridine occurs naturally in potatoes, anabasis, henbane leaves, peppermint (0 to 1 ppb),
tea leaves, and tobacco leaves (Duke, 1992). Identified as one of 140 volatile constituents in used
soybean oils collected from a processing plant that fried various beef, chicken, and veal products
(Takeoka et al., 1996). | [Environmental Fate]
Biological. Heukelekian and Rand (1955) reported a 5-d BOD value of 1.31 g/g which is 58.7%
of the ThOD value of 2.23 g/g. A Nocardia sp. isolated from soil was capable of transforming
pyridine, in the presence of semicarbazide, into an intermediate product identified as succinic acid
semialdehyde (Shukla and Kaul, 1986). 1,4-Dihydropyridine, glutaric dialdehyde, glutaric acid
semialdehyde, and glutaric acid were identified as intermediate products when pyridine was
degraded by Nocardia strain Z1 (Watson and Cain, 1975).
Photolytic. Irradiation of an aqueous solution at 50 °C for 24 h resulted in a 23.06% yield of
carbon dioxide (Knoevenagel and Himmelreich, 1976).
Chemical/Physical. The gas-phase reaction of ozone with pyridine in synthetic air at 23 °C
yielded a nitrated salt having the formula: [C6H5NH]+NO3
- (Atkinson et al., 1987). Ozonation of
pyridine in aqueous solutions at 25 °C was studied with and without the addition of tert-butyl
alcohol (20 mM) as a radical scavenger. With tert-butyl alcohol, ozonation of pyridine yielded
mainly pyridine N-oxide (80% yield), which was very stable towards ozone. Without tert-butyl
alcohol, the heterocyclic ring is rapidly cleaved forming ammonia, nitrate, and the amidic
compound N-formyl oxamic acid (Andreozzi et al., 1991). | [Metabolism]
Pyridine is absorbed through the gastrointestinal tract, skin and lungs and is
eliminated via the urine, feces, skin and lungs, both as metabolites and as the
parent compound (Jori et al 1983). Uptake by tissues increases with dose and the
elimination is biphasic in nature (Zharikov and Titov 1982; HSDB 1988). Elimination
is rapid and there appears to be no tissue accumulation (Jori et al 1983). The
observation by His (1887) of the urinary excretion of Af-methylpyridine by
pyridine-dosed animals was the first example of Af-methylation. Known urinary
metabolites of pyridine in mammals now include pyridine N-oxide, N-methyl
pyridine, 4-pyridone, 2-pyridone and 3-hydroxypyridine. Some metabolites still
remain to be identified (Damani et al 1982). The relative amounts of the metabolites
are highly dependent on the species and dose (Gorrod and Damani 1980). For
example, the rat has been shown to excrete 70% of a 1 mg/kg dose in the urine in
the first 24 h after dosing, but that figure drops to only 5.8% for a 500 mg/kg dose
(D'Souza et al 1980). Although urinary excretion of pyridine and its metabolites
appears to be a major route for elimination, non-urinary excretion has not been
extensively studied (Santodonato et al 1985). In rabbits, the pyridine N-methyltransferase
activity has been shown to be highest in lung cytosol and it has been
found to utilize 5-adenosyl methionine as the methyl donor (Damani et al 1986).
This pathway is saturable in both the rat and the guinea pig (D'Souza et al 1980).
The product of this reaction, N-methyl pyridine, is less chronically toxic but more
acutely toxic than pyridine (Williams 1959). Pyridine N-oxide is produced by the
cytochrome P-450 system and the activity is induced by phenobarbital or pyridine
pretreatment but not by 3-methylcholanthrene (Gorrod and Damani 1979; Kaul
and Novak 1987). In the rabbit, the alcohol-inducible (and pyridine inducible)
P-450 LM3A appears to be the low Km isozyme which catalyzes pyridine Af-oxide
production (Kim and Novak 1989). The N-oxidation of pyridine may represent a
pathway for bioactivation (Santodonato et al 1985) and this pathway becomes
more important as the pyridine dose is increased (Damani et al 1982). | [storage]
Pyridine 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. | [Purification Methods]
Likely impurities are H2O and amines such as the picolines and lutidines. Pyridine is hygroscopic and is miscible with H2O and organic solvents. It can be dried with solid KOH, NaOH, CaO, BaO or sodium, followed by fractional distillation. Other methods of drying include standing with Linde type 4A molecular sieves, CaH2 or LiAlH4, azeotropic distillation of the H2O with toluene or *benzene, or treated with phenylmagnesium bromide in ether, followed by evaporation of the ether and distillation of the pyridine. A recommended [Lindauer & Mukherjee Pure Appl Chem 27 267 1971] method dries pyridine over solid KOH (20g/Kg) for 2weeks and fractionally distils the supernatant over Linde type 5A molecular sieves and solid KOH. The product is stored under CO2-free nitrogen. Pyridine can be stored in contact with BaO, CaH2 or molecular sieves. Non-basic materials can be removed by steam distilling a solution containing 1.2 equivalents of 20% H2SO4 or 17% HCl until about 10% of the base has been carried over along with the non-basic impurities. The residue is then made alkaline, and the base is separated, dried with NaOH and fractionally distilled. Alternatively, pyridine can be treated with oxidising agents. Thus pyridine (800mL) has been stirred for 24hours with a mixture of ceric sulfate (20g) and anhydrous K2CO3 (15g), then filtered and fractionally distilled. Hurd and Simon [J Am Chem Soc 84 4519 1962] stirred pyridine (135mL), water (2.5L) and KMnO4 (90g) for 2hours at 100o, then stood for 15hours before filtering off the precipitated manganese oxides. Addition of solid KOH (ca 500g) caused pyridine to separate. It was decanted, refluxed with CaO for 3hours and distilled. Separation of pyridine from some of its homologues can be achieved by crystallisation of the oxalates. Pyridine is precipitated as its oxalate by adding it to the stirred solution of oxalic acid in acetone. The precipitate is filtered, washed with cold acetone, and pyridine is regenerated and isolated. Other methods are based on complex formation with ZnCl2 or HgCl2. Heap, Jones and Speakman [J Am Chem Soc 43 1936 1921] added crude pyridine (1L) to a solution of ZnCl2 (848g) in 730mL of water, 346mL of conc HCl and 690mL of 95% EtOH. The crystalline precipitate of ZnCl2.(pyridine)2 was filtered off, recrystallised twice from absolute EtOH, then treated with a conc NaOH solution, using 26.7g of solid NaOH to 100g of the complex. The precipitate was filtered off, and the pyridine was dried with NaOH pellets and distilled. Similarly, Kyte, Jeffery and Vogel [J Chem Soc 4454 1960] added pyridine (60mL) in 300mL of 10% (v/v) HCl to a solution of HgCl2 (405g) in hot water (2.3L). On cooling, crystals of pyridine-HgCl2 (1:1) complex separated and were filtered off, crystallised from 1% HCl (to m 178.5-179o), washed with a little EtOH and dried at 110o. The free base was liberated by addition of excess aqueous NaOH and separated by steam distillation. The distillate was saturated with solid KOH, and the upper layer was removed, dried further with KOH, then BaO and distilled. Another possible purification step is fractional crystallisation by partial freezing. Small amounts of pyridine have been purified by vapour-phase chromatography, using a 180-cm column of polyethyleneglycol-400 (Shell 5%) on Embacel at 100o, with argon as carrier gas. The Karl Fischer titration can be used for determining water content. A colour test for pyrrole as a contaminant is described by Biddiscombe et al. [J Chem Soc 1957 1954]. The 1:1-hydrochloride crystallises from EtOH with m 144o, b 218-219o/760mm (see below) and is hygroscopic. The 1:2-hydrochloride has m 46o [58888-58-7] and the picrate has m 165-166o [1152-90-5]. [Beilstein 20 H 181, 20 I 54, 20 II 96, 20 III/IV 2205, 20/5 V 160.] § Polystyrene-supported pyridine is commercially available. |
| Safety Data | Back Directory | [Hazard Codes ]
T,N,F,Xn | [Risk Statements ]
R11:Highly Flammable.
R20/21/22:Harmful by inhalation, in contact with skin and if swallowed .
R39/23/24/25:Toxic: danger of very serious irreversible effects through inhalation, in contact with skin and if swallowed .
R23/24/25:Toxic by inhalation, in contact with skin and if swallowed . | [Safety Statements ]
S36/37/39:Wear suitable protective clothing, gloves and eye/face protection .
S38:In case of insufficient ventilation, wear suitable respiratory equipment .
S45:In case of accident or if you feel unwell, seek medical advice immediately (show label where possible) .
S61:Avoid release to the environment. Refer to special instructions safety data sheet .
S26:In case of contact with eyes, rinse immediately with plenty of water and seek medical advice .
S28:After contact with skin, wash immediately with plenty of ... (to be specified by the manufacturer) .
S24/25:Avoid contact with skin and eyes .
S22:Do not breathe dust .
S36/37:Wear suitable protective clothing and gloves .
S16:Keep away from sources of ignition-No smoking .
S7:Keep container tightly closed . | [RIDADR ]
UN 1282 3/PG 2
| [WGK Germany ]
2
| [RTECS ]
UR8400000
| [F ]
3-10 | [Autoignition Temperature]
482 °C | [Hazard Note ]
Highly Flammable/Harmful | [TSCA ]
Yes | [HazardClass ]
3 | [PackingGroup ]
II | [HS Code ]
29333100 | [Safety Profile]
Poison by intraperitoneal route. Moderately toxic by ingestion, skin contact, intravenous, and subcutaneous routes. Mildly toxic by inhalation. A skin and severe eye irritant. Mutation data reported. Can cause central nervous system depression, gastrointestinal
upset, and liver and kidney damage. A flammable liquid and dangerous fire hazard when exposed to heat, flame, or oxidizers. Severe explosion hazard in the form of vapor when exposed to flame or spark. Reacts violently with chlorosulfonic acid, chromium trioxide, dinitrogen tetraoxide, HNO3, oleum, perchromates, ppropiolactone, AgClO4, H2SO4. Incandescent reaction with fluorine. Reacts to form pyrophoric or explosive products with bromine trifluoride, trifluoromethyl hypofluorite. Mixtures with formamide + iodine + sulfur trioxide are storage hazards, releasing carbon dioxide and sulfuric acid. Incompatible with oxidizing materials. Reacts with maleic anhydride (above 150°C) evolving carbon dioxide. To fight fire, use alcohol foam. When heated to decomposition it emits highly toxic fumes of NOx. | [Hazardous Substances Data]
110-86-1(Hazardous Substances Data) | [Toxicity]
LD50 orally in rats: 1.58 g/kg (Smyth) | [IDLA]
1,000 ppm |
| Raw materials And Preparation Products | Back Directory | [Raw materials]
Sulfuric acid-->Ammonia-->Benzene-->COAL TAR-->3-Picoline-->COKEOVENGAS-->1,5-DIAMINOPENTANE DIHYDROCHLORIDE | [Preparation Products]
Methyl 2-Fluoroisonicotinate-->2-ACETYL-5-CYANOTHIOPHENE-->5-BROMO-2-FLUOROCINNAMIC ACID-->4-NITROISOPHTHALIC ACID-->3,5-DIMETHOXYCINNAMIC ACID-->2-(2-Butoxyethoxy)ethyl acetate-->2,4-MESITYLENEDISULFONYL DICHLORIDE-->(4-FLUORO-BENZYL)-METHYL-AMINE-->1-Phenacylpyridinium bromide-->3-(TRIFLUOROMETHOXY)CINNAMIC ACID-->trans-Ferulic acid-->3-(Trifluoromethyl)pyrazole-->4-Fluorocinnamic acid-->Indigosol Green Blue IBC-->2-Amino-4-methyl-5-acetylthiazole-->Benzyl 2-chloroacetate-->5-ACETAMIDONICOTINIC ACID-->7-ACETOXYCOUMARIN-->2-AMINO-4-METHYL-QUINOLINE-3-CARBONITRILE-->N-PHENYLISONICOTINAMIDE-->Allyl methyl carbonate-->Pyridine-3-sulfonyl chloride hydrochloride-->Syringaldehyde-->2,4,5,6-TETRAMETHYLBENZENEDISULFONYL DICHLORIDE-->3-(3-METHYL-2-THIENYL)ACRYLIC ACID-->Vat Grey M-->17beta-Hydroxy-17-methylandrosta-4,9(11)-dien-3-one-->butyl N-phenylcarbamate-->3-Methoxycinnamic acid-->1-CHLORO-2-METHYLPROPYL CHLOROFORMATE-->Pyrazinecarbonitrile-->2-AMINO-6-CHLORO-3,5-DICYANOPYRIDINE-->4-BROMO-TETRAHYDROPYRAN-->Phenylcarbamic acid propyl ester-->Hydrocortisone acetate-->5-METHYLPICOLINIC ACID-->4-Acetamido-2-chloropyridine-->Pyridinium p-Toluenesulfonate-->1,2,4-Triazolo[4,3-a]pyridin-3(2H)-one-->Paraquat dichloride |
| Questions And Answer | Back Directory | [Chemical Structure]
Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one methine group (=CH−) replaced by a nitrogen atom. The pyridine ring occurs in many important compounds, including azines and the vitamins niacin and pyridoxine.
Pyridine Lewis structure | [Chemical properties]
Pyridine is a colourless flammable liquid with a strong and unpleasant fish-like odour.
Pyridine
| [Productions]
2.1 Separation from Tar
Pyridine bases are a constituent of tars. They were isolated from coal tar or coal gas before synthetic manufacturing processes became established. The amounts contained in coal tar and coal gas is small, and the pyridine bases isolated from them are a mixture of many components. Thus, with a few exceptions, isolation of pure pyridine bases was expensive. Today, almost all pyridine bases are produced by synthesis.2.2 Chichibabin synthesis
Fig. 2-1 Formation of acrolein from acetaldehyde and formaldehyde
Fig. 2-2 Condensation of pyridine from acrolein and acetaldehyde
The Chichibabin pyridine synthesis was reported in 1924 and is still in use in industry. Acetaldehyde and formaldehyde react with ammonia to give mainly pyridine. First, acrolein is formed in a Knoevenagel condensation from the acetaldehyde and formaldehyde. It is then condensed with acetaldehyde and ammonia into dihydropyridine, and then oxidized with a solid-state catalyst to pyridine. The reaction is usually carried out at 350-550°C and a space velocity of 500-1000 h -1 in the presence of a solid acid catalyst (e.g., silica-alumina). The product consists of a mixture of pyridine, simple methylated pyridines (picoline), and lutidine. The recovered pyridine is separated from byproducts in a multistage process.
Fig. 2-3 Flow sheet of pyridine and methylpyridine production from acetaldehyde and formaldehyde with ammonia. A) Reactor; b) Collector; c) Extraction; d) Solvent distillation; e) Distillation
2.3 Dealkylation of Alkylpyridines
Pyridine can be prepared by dealkylation of alkylated pyridines, which are obtained as byproducts in the syntheses of other pyridines. The oxidative dealkylation is carried out either using air over vanadium(V) oxide catalyst, by vapor-dealkylation on nickel-based catalyst, or hydrodealkylation with a silver- or platinum-based catalyst. Yields of pyridine up to be 93% can be achieved with the nickel-based catalyst.
2.4 Synthesis from Nitriles and Acetylene
Liquid-phase reaction of nitriles with acetylene is carried out at 120-180 ?C and 0.8-2.5 MPa in the presence of an organocobalt catalyst and gives 2-substituted pyridines:
Fig. 2-4 Synthesis of 2-methylpyridine from nitriles and acetylene
The trimerization of a part of a nitrile molecule and two parts of acetylene into pyridine is called Bönnemann cyclization. When using acetonitrile as the nitrile, 2-methylpyridine is obtained, which can be dealkylated to pyridine.
2.5 Synthesis from Acrylonitrile and Ketones
Fig. 2-5 Synthesis of 2-methylpyridine from acrylonitrile and acetone
Synthesis from acrylonitrile and acetone gives 2-methylpyridine selectively, which can be dealkylated to pyridine. First, the reaction of acrylonitrile and acetone, catalyzed by a primary aliphatic amine such as isopropylamine and a weak acid such as benzoic acid, occurs in the liquid phase at 180 ?C and 2.2 MPa to give 5-oxohexanenitrile, with 91% selectivity. The acrylonitrile conversion is 86%. Then cyclization and dehydration of the initial product are carried out in the gas phase in the presence of hydrogen over a palladium, nickel, or cobalt-containing catalyst at 240?C to give 2-methylpyridine in 84% yield.
2.6 Synthesis from Dinitriles
In a vapor-phase reaction over a nickel-containing catalyst in the presence of hydrogen, 2-methylglutaronitrile gives 3-methylpiperidine, which then undergoes dehydrogenation over palladium –alumina to give 3-methylpyridine. And 3-methylpyridine also can be dealkylated to pyridine.
Fig. 2-6 Synthesis of 2-methylpyridine from Dinitriles
A one-step gas-phase reaction over a palladium-containing catalyst is reported to give 3-methylpyridine in 50% yield.
2.7 Biosynthesis
Several pyridine derivatives play important roles in biological systems. While its biosynthesis is not fully understood, nicotinic acid (vitamin B3) occurs in some bacteria, fungi, and mammals. Mammals synthesize nicotinic acid through oxidation of the amino acid tryptophan, where an intermediate product, aniline, creates a pyridine derivative, kynurenine. On the contrary, the bacteria Mycobacterium tuberculosis and Escherichia coli produce nicotinic acid by condensation of glyceraldehyde 3-phosphate and aspartic acid.
2.8 Other methods
Ethylene and ammonia react in the presence of a palladium complex catalyst to give 2-methylpyridine and MEP. Pyridine can be prepared from cyclopentadiene by ammoxidation, or from 2-pentenenitrile by cyclization and dehydrogenation. Furfuryl alcohol or furfural reacts with ammonia in the gas phase to give pyridine. 2-Methylpyridine is also prepared from aniline. | [Uses]
3.1 Solvent
Pyridine(110-86-1) is a polar, basic, low-reactive solvent, especially for dehydrochlorination reactions and extraction of antibiotics. In elimination reaction, pyridine acts as the base of the elimination reaction and bonds the resulting hydrogen halide to form a pyridinium salt. In esterifications and acylations, pyridine activates the carboxylic acid halides or anhydrides.
3.2 Medicines
Pyridine's chemical structure can be found in various medications that are synthesized thanks in part to pyridine. One example is a medication called esomeprazole, the generic name for Nexium. This is a medication that's used to treat GERD, or gastroesophageal reflux disease. Another example of a pyridine containing medication is loratadine, more commonly known by its brand name of Claritin. Loratadine helps in the treatment of allergies.
3.3 Pesticides
The main use of pyridine is as a precursor to the herbicides paraquat and diquat. The first synthesis step of insecticide chlorpyrifos consists of the chlorination of pyridine. Pyridine is also the starting compound for the preparation of pyrithione-based fungicides. Cetylpyridinium and laurylpyridinium, which can be produced from pyridine with a Zincke reaction, are used as antiseptic in oral and dental care products. Pyridine is easily attacked by alkylating agents to give N-alkylpyridinium salts. One example is cetylpyridinium chloride.
Fig 3-1 Synthesis of paraquat
3.4 Synthesis of piperidine
Piperidine, a fundamental nitrogen heterocycle, is important synthetic building-block. Piperidines are produced by hydrogenation of pyridine with a nickel-, cobalt-, or ruthenium-based catalyst at elevated temperatures.
C5H5N + 3 H2 → C5H10NH3.5 Ligand and Lewis base
Pyridine is widely used as a ligand in coordination chemistry. As a ligand of metal complex, it can be easily replaced by a stronger Lewis base, which can be used in the catalysis of polymerization and hydrogenation reactions. After the completion of reaction, pyridine ligand replaced during the reaction can be restored again. Pyridine is also used as a base in condensation reactions. As a base, pyridine can be used as the Karl Fischer reagent, but it is usually replaced by alternatives with a more pleasant odor, such as imidazole.
3.6 Others
Except for above uses, Pyridine is also used to product polycarbonate resins, vitamins, food flavorings, paints, dyes, rubber products, adhesives, and waterproofing for fabrics. Pyridine is added to ethanol to make it unsuitable for drinking. It is also used in the in vitro synthesis of DNA.
| [Toxicity information]
4.1 Toxicity Level
Low Toxicity
4.2 Acute Toxicity
LD501580mg/kg (Large mice, oral); 1121mg/kg (Rabbit, through skin); inhaled by human 25mg/m3×20 min, irritation of conjunctiva and upper respiratory tract mucosa. Subacute and chronic toxicity: inhaled by large mice 32.3mg/m3×7 hours/day x5 days/week x6 months, increase in liver weight; inhaled by humans 20～40mg/m3 (long term), nerve damage, unsteady walking, digital tremors, low blood pressure, over-sweating, occasional liver and kidney damage.
| [Hazards]
5.1 Health hazards
Pyridine is extremely toxic by ingestion and inhalation. Vapors are heavier than air. its combustion produces toxic oxides of nitrogen. Pyridine is highly flammable (its flash point is just 17 ºC). Pyridine also could have neurotoxic and genotoxic effects.
5.2 Fire Hazards
Behavior in Fire: Vapor is heavier than air and may travel considerable distance to source of ignition and flash back.
| [References]
- https://en.wikipedia.org/wiki/Pyridine#Occurrence
- http://www.zwbk.org/MyLemmaShow.aspx?zh=zh-tw&lid=169038
- http://www.softschools.com/formulas/chemistry/pyridine_formula/378/
- http://www.hmdb.ca/metabolites/HMDB0000926
- https://study.com/academy/lesson/pyridine-in-medicine-uses-synthesis.html#partialRegFormModal
- http://www.toxipedia.org/display/toxipedia/Pyridine
- https://www.chemicalbook.com/ProductChemicalPropertiesCB8852825_EN.htm
- https://pubchem.ncbi.nlm.nih.gov/compound/pyridine#section=Top
- http://www.ebi.ac.uk/chebi/searchId.do;jsessionid=E7088896622D62FC650863C2AD197CAA?chebiId=CHEBI:16227
- https://www.britannica.com/science/pyridine
- Shimizu, S.; Watanabe, N.; Kataoka, T.; Shoji, T.; Abe, N.; Morishita, S.; Ichimura, H. (2005), "Pyridine and Pyridine Derivatives", Ullmann's Encyclopedia of Industrial Chemistry, Weinheim: Wiley-VCH, doi:10.1002/14356007.a22_399
|
|
|