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53-394: Para - Methoxy ethyl amphetamine ( PMEA ), is a stimulant drug related to PMA . PMEA reputedly produces similar effects to PMA, but is considerably less potent and seems to have slightly less tendency to produce severe hyperthermia , at least at low doses. At higher doses however the side effects and danger of death approach those of PMA itself, and PMEA should still be considered

106-471: A C 5 N hexagon. Slight variations of the C−C and C−N distances as well as the bond angles are observed. Pyridine crystallizes in an orthorhombic crystal system with space group Pna2 1 and lattice parameters a  = 1752  pm , b  = 897 pm, c  = 1135 pm, and 16 formula units per unit cell (measured at 153 K). For comparison, crystalline benzene

159-472: A nitrogen atom (=N−) . It is a highly flammable, weakly alkaline , water-miscible liquid with a distinctive, unpleasant fish-like smell. Pyridine is colorless, but older or impure samples can appear yellow, due to the formation of extended, unsaturated polymeric chains, which show significant electrical conductivity . The pyridine ring occurs in many important compounds, including agrochemicals , pharmaceuticals , and vitamins . Historically, pyridine

212-500: A silver - or platinum -based catalyst. Yields of pyridine up to be 93% can be achieved with the nickel-based catalyst. Pyridine can also be produced by the decarboxylation of nicotinic acid with copper chromite . The trimerization of a part of a nitrile molecule and two parts of acetylene into pyridine is called Bönnemann cyclization . This modification of the Reppe synthesis can be activated either by heat or by light . While

265-477: A byproduct of coal gasification . The process is labor-consuming and inefficient: coal tar contains only about 0.1% pyridine, and therefore a multi-stage purification was required, which further reduced the output. Nowadays, most pyridines are synthesized from ammonia, aldehydes, and nitriles, a few combinations of which are suited for pyridine itself. Various name reactions are also known, but they are not practiced on scale. In 1989, 26,000 tonnes of pyridine

318-448: A fairly general method for generating substituted pyridines using pyridine itself as a reagent which does not become incorporated into the final product. The reaction of pyridine with bromomethyl ketones gives the related pyridinium salt, wherein the methylene group is highly acidic. This species undergoes a Michael-like addition to α,β-unsaturated carbonyls in the presence of ammonium acetate to undergo ring closure and formation of

371-406: A heteroaromatic compound. The first major synthesis of pyridine derivatives was described in 1881 by Arthur Rudolf Hantzsch . The Hantzsch pyridine synthesis typically uses a 2:1:1 mixture of a β- keto acid (often acetoacetate ), an aldehyde (often formaldehyde ), and ammonia or its salt as the nitrogen donor. First, a double hydrogenated pyridine is obtained, which is then oxidized to

424-465: A leaving group. So fluorine is the best leaving group for the substitution with organolithium compounds . The nucleophilic attack compounds may be alkoxides , thiolates, amines , and ammonia (at elevated pressures). In general, the hydride ion is a poor leaving group and occurs only in a few heterocyclic reactions. They include the Chichibabin reaction , which yields pyridine derivatives aminated at

477-425: A nucleophile to the triple bond has low selectivity, and the result is a mixture of the two possible adducts. Pyridine supports a series of radical reactions, which is used in its dimerization to bipyridines. Radical dimerization of pyridine with elemental sodium or Raney nickel selectively yields 4,4'-bipyridine , or 2,2'-bipyridine , which are important precursor reagents in the chemical industry. One of

530-537: A positive mesomeric effect . Many analogues of pyridine are known where N is replaced by other heteroatoms from the same column of the Periodic Table of Elements (see figure below). Substitution of one C–H in pyridine with a second N gives rise to the diazine heterocycles (C 4 H 4 N 2 ), with the names pyridazine , pyrimidine , and pyrazine . Impure pyridine was undoubtedly prepared by early alchemists by heating animal bones and other organic matter, but

583-477: A positive charge in the ring that increases the reactivity of pyridine to both oxidation and reduction. The Zincke reaction is used for the selective introduction of radicals in pyridinium compounds (it has no relation to the chemical element zinc ). Piperidine is produced by hydrogenation of pyridine with a nickel -, cobalt -, or ruthenium -based catalyst at elevated temperatures. The hydrogenation of pyridine to piperidine releases 193.8 kJ/mol, which

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636-607: A potentially dangerous drug. Investigation of a drug-related death in Japan in 2005 showed PMEA to be present in the body and was thought to be responsible for the death. Stimulants: Phenylethanolamine Para isomer The toluidines serve as an example for these three types of substitution. Electron donating groups, for example amino , hydroxyl , alkyl , and phenyl groups tend to be ortho / para -directors, and electron withdrawing groups such as nitro , nitrile , and ketone groups, tend to be meta -directors. Although

689-458: A single line at 129 ppm. All shifts are quoted for the solvent-free substances. Pyridine is conventionally detected by the gas chromatography and mass spectrometry methods. Pyridine has a conjugated system of six π electrons that are delocalized over the ring. The molecule is planar and, thus, follows the Hückel criteria for aromatic systems. In contrast to benzene, the electron density

742-400: Is basic , having chemical properties similar to those of tertiary amines . Protonation gives pyridinium , C 5 H 5 NH .The p K a of the conjugate acid (the pyridinium cation) is 5.25. The structures of pyridine and pyridinium are almost identical. The pyridinium cation is isoelectronic with benzene. Pyridinium p - toluenesulfonate (PPTS) is an illustrative pyridinium salt; it

795-544: Is a sulfation agent used to convert alcohols to sulfate esters . Pyridine- borane ( C 5 H 5 NBH 3 , melting point 10–11 °C) is a mild reducing agent. Transition metal pyridine complexes are numerous. Typical octahedral complexes have the stoichiometry MCl 2 (py) 4 and MCl 3 (py) 3 . Octahedral homoleptic complexes of the type M(py) + 6 are rare or tend to dissociate pyridine. Numerous square planar complexes are known, such as Crabtree's catalyst . The pyridine ligand replaced during

848-426: Is also orthorhombic, with space group Pbca , a  = 729.2 pm, b  = 947.1 pm, c  = 674.2 pm (at 78 K), but the number of molecules per cell is only 4. This difference is partly related to the lower symmetry of the individual pyridine molecule (C 2v vs D 6h for benzene). A tri hydrate (pyridine·3H 2 O) is known; it also crystallizes in an orthorhombic system in

901-407: Is in an sp orbital, projecting outward from the ring in the same plane as the σ bonds . As a result, the lone pair does not contribute to the aromatic system but importantly influences the chemical properties of pyridine, as it easily supports bond formation via an electrophilic attack. However, because of the separation of the lone pair from the aromatic ring system, the nitrogen atom cannot exhibit

954-455: Is not evenly distributed over the ring, reflecting the negative inductive effect of the nitrogen atom. For this reason, pyridine has a dipole moment and a weaker resonant stabilization than benzene ( resonance energy 117 kJ/mol in pyridine vs. 150 kJ/mol in benzene). The ring atoms in the pyridine molecule are sp -hybridized . The nitrogen is involved in the π-bonding aromatic system using its unhybridized p orbital. The lone pair

1007-527: Is not fully understood, nicotinic acid (vitamin B 3 ) occurs in some bacteria , fungi , and mammals . Mammals synthesize nicotinic acid through oxidation of the amino acid tryptophan , where an intermediate product, the aniline derivative kynurenine , creates a pyridine derivative, quinolinate and then nicotinic acid. On the contrary, the bacteria Mycobacterium tuberculosis and Escherichia coli produce nicotinic acid by condensation of glyceraldehyde 3-phosphate and aspartic acid . Because of

1060-501: Is obtained by electrochemical reduction of pyridine. Birch reduction converts pyridine to dihydropyridines. Pyridine is a Lewis base , donating its pair of electrons to a Lewis acid. Its Lewis base properties are discussed in the ECW model . Its relative donor strength toward a series of acids, versus other Lewis bases, can be illustrated by C-B plots . One example is the sulfur trioxide pyridine complex (melting point 175 °C), which

1113-531: Is oxidized to pyridine. This process is carried out in a gas phase at 400–450 °C. Typical catalysts are modified forms of alumina and silica . The reaction has been tailored to produce various methylpyridines . 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

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1166-578: Is produced by treating pyridine with p -toluenesulfonic acid . In addition to protonation , pyridine undergoes N-centred alkylation , acylation , and N -oxidation . Pyridine and poly(4-vinyl) pyridine have been shown to form conducting molecular wires with remarkable polyenimine structure on UV irradiation , a process which accounts for at least some of the visible light absorption by aged pyridine samples. These wires have been theoretically predicted to be both highly efficient electron donors and acceptors, and yet are resistant to air oxidation. Owing to

1219-464: Is slightly less than the energy of the hydrogenation of benzene (205.3 kJ/mol). Partially hydrogenated derivatives are obtained under milder conditions. For example, reduction with lithium aluminium hydride yields a mixture of 1,4-dihydropyridine, 1,2-dihydropyridine, and 2,5-dihydropyridine. Selective synthesis of 1,4-dihydropyridine is achieved in the presence of organometallic complexes of magnesium and zinc , and (Δ3,4)-tetrahydropyridine

1272-451: Is sluggish. Pyridine derivatives wherein the nitrogen atom is screened sterically and/or electronically can be obtained by nitration with nitronium tetrafluoroborate (NO 2 BF 4 ). In this way, 3-nitropyridine can be obtained via the synthesis of 2,6-dibromopyridine followed by nitration and debromination. Sulfonation of pyridine is even more difficult than nitration. However, pyridine-3-sulfonic acid can be obtained. Reaction with

1325-730: The electronegative nitrogen in the pyridine ring, pyridine enters less readily into electrophilic aromatic substitution reactions than benzene derivatives. Instead, in terms of its reactivity, pyridine resembles nitrobenzene . Correspondingly pyridine is more prone to nucleophilic substitution , as evidenced by the ease of metalation by strong organometallic bases. The reactivity of pyridine can be distinguished for three chemical groups. With electrophiles , electrophilic substitution takes place where pyridine expresses aromatic properties. With nucleophiles , pyridine reacts at positions 2 and 4 and thus behaves similar to imines and carbonyls . The reaction with many Lewis acids results in

1378-453: The name reactions involving free radicals is the Minisci reaction . It can produce 2- tert -butylpyridine upon reacting pyridine with pivalic acid , silver nitrate and ammonium in sulfuric acid with a yield of 97%. Lewis acids easily add to the nitrogen atom of pyridine, forming pyridinium salts. The reaction with alkyl halides leads to alkylation of the nitrogen atom. This creates

1431-427: The nitrogen atom is considered one of the substituents. For example, nicotinamide and niacin , shown meta substitutions on a pyridine ring, while the cation of pralidoxime is an ortho isomer. Pyridine Pyridine is a basic heterocyclic organic compound with the chemical formula C 5 H 5 N . It is structurally related to benzene , with one methine group (=CH−) replaced by

1484-431: The ortho isomer catechol , the meta isomer resorcinol , and the para isomer hydroquinone : There are three arene substitution isomers of benzenedicarboxylic acid (C 6 H 4 (COOH) 2 ) – the ortho isomer phthalic acid , the meta isomer isophthalic acid , and the para isomer terephthalic acid : These terms can also be used in six-membered heterocyclic aromatic systems such as pyridine , where

1537-460: The racemic form of tartaric acid "paratartaric acid" (another obsolete term: racemic acid ) in 1830. The use of the prefixes ortho , meta and para to distinguish isomers of disubstituted aromatic rings starts with Wilhelm Körner in 1867, although he applied the ortho prefix to a 1,4-isomer and the meta prefix to a 1,2-isomer. It was the German chemist Karl Gräbe who, in 1869, first used

1590-470: The thermal activation requires high pressures and temperatures, the photoinduced cycloaddition proceeds at ambient conditions with CoCp 2 (cod) (Cp = cyclopentadienyl, cod = 1,5-cyclooctadiene ) as a catalyst, and can be performed even in water. A series of pyridine derivatives can be produced in this way. When using acetonitrile as the nitrile, 2-methylpyridine is obtained, which can be dealkylated to pyridine. The Kröhnke pyridine synthesis provides

1643-458: The volatile organic compounds that are produced in roasting and canning processes, e.g. in fried chicken, sukiyaki , roasted coffee, potato chips, and fried bacon . Traces of pyridine can be found in Beaufort cheese , vaginal secretions , black tea , saliva of those suffering from gingivitis , and sunflower honey . Historically, pyridine was extracted from coal tar or obtained as

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1696-525: The 2-position. Here, sodium amide is used as the nucleophile yielding 2-aminopyridine. The hydride ion released in this reaction combines with a proton of an available amino group, forming a hydrogen molecule. Analogous to benzene, nucleophilic substitutions to pyridine can result in the formation of pyridyne intermediates as hetero aryne . For this purpose, pyridine derivatives can be eliminated with good leaving groups using strong bases such as sodium and potassium tert-butoxide . The subsequent addition of

1749-468: The SO 3 group also facilitates addition of sulfur to the nitrogen atom, especially in the presence of a mercury(II) sulfate catalyst. In contrast to the sluggish nitrations and sulfonations, the bromination and chlorination of pyridine proceed well. Oxidation of pyridine occurs at nitrogen to give pyridine N -oxide . The oxidation can be achieved with peracids : Some electrophilic substitutions on

1802-518: The above, in ammonia or ammonia derivatives . Application of the Chichibabin pyridine synthesis suffer from low yields, often about 30%, however the precursors are inexpensive. In particular, unsubstituted pyridine is produced from formaldehyde and acetaldehyde . First, acrolein is formed in a Knoevenagel condensation from the acetaldehyde and formaldehyde. The acrolein then condenses with acetaldehyde and ammonia to give dihydropyridine , which

1855-399: The addition to the nitrogen atom of pyridine, which is similar to the reactivity of tertiary amines. The ability of pyridine and its derivatives to oxidize, forming amine oxides ( N -oxides), is also a feature of tertiary amines. The nitrogen center of pyridine features a basic lone pair of electrons . This lone pair does not overlap with the aromatic π-system ring, consequently pyridine

1908-413: The carbon atoms of the ring. These reactions include substitutions with elimination of a hydride ion and elimination-additions with formation of an intermediate aryne configuration, and usually proceed at the 2- or 4-position. Many nucleophilic substitutions occur more easily not with bare pyridine but with pyridine modified with bromine, chlorine, fluorine, or sulfonic acid fragments that then become

1961-483: The corresponding pyridine derivative. Emil Knoevenagel showed that asymmetrically substituted pyridine derivatives can be produced with this process. The contemporary methods of pyridine production had a low yield, and the increasing demand for the new compound urged to search for more efficient routes. A breakthrough came in 1924 when the Russian chemist Aleksei Chichibabin invented a pyridine synthesis reaction , which

2014-431: The current meaning is perhaps not obvious. The ortho description was historically used to designate the original compound, and an isomer was often called the meta compound. For instance, the trivial names orthophosphoric acid and trimetaphosphoric acid have nothing to do with aromatics at all. Likewise, the description para was reserved for just closely related compounds. Thus Jöns Jakob Berzelius originally called

2067-463: The decreased electron density in the aromatic system, electrophilic substitutions are suppressed in pyridine and its derivatives. Friedel–Crafts alkylation or acylation , usually fail for pyridine because they lead only to the addition at the nitrogen atom. Substitutions usually occur at the 3-position, which is the most electron-rich carbon atom in the ring and is, therefore, more susceptible to an electrophilic addition. Direct nitration of pyridine

2120-588: The earliest documented reference is attributed to the Scottish scientist Thomas Anderson . In 1849, Anderson examined the contents of the oil obtained through high-temperature heating of animal bones . Among other substances, he separated from the oil a colorless liquid with unpleasant odor, from which he isolated pure pyridine two years later. He described it as highly soluble in water, readily soluble in concentrated acids and salts upon heating, and only slightly soluble in oils. Owing to its flammability, Anderson named

2173-467: The early 2000s, with an annual production capacity of 30,000 tonnes in mainland China alone. The US–Chinese joint venture Vertellus is currently the world leader in pyridine production. The Chichibabin pyridine synthesis was reported in 1924 and the basic approach underpins several industrial routes. In its general form, the reaction involves the condensation reaction of aldehydes , ketones , α,β-unsaturated carbonyl compounds , or any combination of

para-Methoxy-N-ethylamphetamine - Misplaced Pages Continue

2226-433: The new substance pyridine , after Greek : πῦρ (pyr) meaning fire . The suffix idine was added in compliance with the chemical nomenclature, as in toluidine , to indicate a cyclic compound containing a nitrogen atom. The chemical structure of pyridine was determined decades after its discovery. Wilhelm Körner (1869) and James Dewar (1871) suggested that, in analogy between quinoline and naphthalene ,

2279-591: The prefixes ortho -, meta -, para - to denote specific relative locations of the substituents on a disubstituted aromatic ring (namely naphthalene ). In 1870, the German chemist Viktor Meyer first applied Gräbe's nomenclature to benzene . The current nomenclature was introduced by the Chemical Society in 1879. Examples of the use of this nomenclature are given for isomers of cresol , C 6 H 4 (OH)(CH 3 ): There are three arene substitution isomers of dihydroxybenzene (C 6 H 4 (OH) 2 ) –

2332-528: The proton signal for benzene is found at δ7.27. The larger chemical shifts of the α- and γ-protons in comparison to benzene result from the lower electron density in the α- and γ-positions, which can be derived from the resonance structures. The situation is rather similar for the C ;NMR spectra of pyridine and benzene: pyridine shows a triplet at δ (α-C) = 150 ppm, δ(β-C) = 124 ppm and δ(γ-C) = 136 ppm, whereas benzene has

2385-420: The pyridine are usefully effected using pyridine N -oxide followed by deoxygenation. Addition of oxygen suppresses further reactions at nitrogen atom and promotes substitution at the 2- and 4-carbons. The oxygen atom can then be removed, e.g., using zinc dust. In contrast to benzene ring, pyridine efficiently supports several nucleophilic substitutions. The reason for this is relatively lower electron density of

2438-405: The reaction is restored after its completion. The η coordination mode, as occurs in η benzene complexes, is observed only in sterically encumbered derivatives that block the nitrogen center. 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

2491-684: The space group Pbca , lattice parameters a  = 1244 pm, b  = 1783 pm, c  = 679 pm and eight formula units per unit cell (measured at 223 K). The optical absorption spectrum of pyridine in hexane consists of bands at the wavelengths of 195, 251, and 270 nm. With respective extinction coefficients ( ε ) of 7500, 2000, and 450 L·mol ·cm , these bands are assigned to π → π*, π → π*, and n → π* transitions. The compound displays very low fluorescence . The H nuclear magnetic resonance (NMR) spectrum shows signals for α-( δ 8.5), γ-(δ7.5) and β-protons (δ7). By contrast,

2544-629: The specifics vary depending on the compound, in simple disubstituted arenes, the three isomers tend to have rather similar boiling points. However, the para isomer usually has the highest melting point, and the lowest solubility in a given solvent, of the three isomers. Because electron donating groups are both ortho and para directors, separation of these isomers is a common problem in synthetic chemistry. Several methods exist in order to separate these isomers: The prefixes ortho , meta , and para are all derived from Greek, meaning correct , following , and beside , respectively. The relationship to

2597-400: The structure of pyridine is derived from benzene by substituting one C–H unit with a nitrogen atom. The suggestion by Körner and Dewar was later confirmed in an experiment where pyridine was reduced to piperidine with sodium in ethanol . In 1876, William Ramsay combined acetylene and hydrogen cyanide into pyridine in a red-hot iron-tube furnace. This was the first synthesis of

2650-613: The targeted substituted pyridine as well as pyridinium bromide. The Ciamician–Dennstedt rearrangement entails the ring-expansion of pyrrole with dichlorocarbene to 3-chloropyridine . In the Gattermann–Skita synthesis, a malonate ester salt reacts with dichloro methylamine . Other methods include the Boger pyridine synthesis and Diels–Alder reaction of an alkene and an oxazole . Several pyridine derivatives play important roles in biological systems. While its biosynthesis

2703-405: Was based on inexpensive reagents. This method is still used for the industrial production of pyridine. Pyridine is not abundant in nature, except for the leaves and roots of belladonna ( Atropa belladonna ) and in marshmallow ( Althaea officinalis ). Pyridine derivatives, however, are often part of biomolecules such as alkaloids . In daily life, trace amounts of pyridine are components of

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2756-553: Was produced from coal tar . As of 2016, it is synthesized on the scale of about 20,000 tons per year worldwide. Pyridine is diamagnetic . Its critical parameters are: pressure 5.63 MPa, temperature 619 K and volume 248 cm /mol. In the temperature range 340–426 °C its vapor pressure p can be described with the Antoine equation where T is temperature, A  = 4.16272, B  = 1371.358 K and C  = −58.496 K. Pyridine ring forms

2809-542: Was produced worldwide. Other major derivatives are 2- , 3- , 4-methylpyridines and 5-ethyl-2-methylpyridine . The combined scale of these alkylpyridines matches that of pyridine itself. Among the largest 25 production sites for pyridine, eleven are located in Europe (as of 1999). The major producers of pyridine include Evonik Industries , Rütgers Chemicals, Jubilant Life Sciences, Imperial Chemical Industries , and Koei Chemical. Pyridine production significantly increased in

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