Anisole

Last updated
Anisole
Anisol.svg
Anisole-3D-balls.png
Anisole.jpg
Names
Preferred IUPAC name
Anisole [1]
Systematic IUPAC name
Methoxybenzene [1]
Other names
Methyl phenyl ether [1]
Phenoxymethane
Identifiers
3D model (JSmol)
506892
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.002.615 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 202-876-1
2964
KEGG
PubChem CID
RTECS number
  • BZ8050000
UNII
UN number 2222
  • InChI=1S/C7H8O/c1-8-7-5-3-2-4-6-7/h2-6H,1H3 Yes check.svgY
    Key: RDOXTESZEPMUJZ-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C7H8O/c1-8-7-5-3-2-4-6-7/h2-6H,1H3
    Key: RDOXTESZEPMUJZ-UHFFFAOYAP
  • COc1ccccc1
Properties
C7H8O
Molar mass 108.140 g·mol−1
AppearanceColorless liquid
Density 0.995 g/cm3
Melting point −37 °C (−35 °F; 236 K)
Boiling point 154 °C (309 °F; 427 K)
Solubility Insoluble
−72.79×10−6 cm3/mol
Hazards
GHS labelling:
GHS-pictogram-flamme.svg GHS-pictogram-exclam.svg
Warning
H226, H315, H319
P210, P233, P240, P241, P242, P243, P264, P280, P302+P352, P303+P361+P353, P305+P351+P338, P321, P332+P313, P337+P313, P362, P370+P378, P403+P235, P501
NFPA 704 (fire diamond)
NFPA 704.svgHealth 1: Exposure would cause irritation but only minor residual injury. E.g. turpentineFlammability 2: Must be moderately heated or exposed to relatively high ambient temperature before ignition can occur. Flash point between 38 and 93 °C (100 and 200 °F). E.g. diesel fuelInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
1
2
0
Lethal dose or concentration (LD, LC):
3700 mg/kg (rat, oral)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Anisole, or methoxybenzene, is an organic compound with the formula CH3OC6H5. It is a colorless liquid with a smell reminiscent of anise seed, and in fact many of its derivatives are found in natural and artificial fragrances. The compound is mainly made synthetically and is a precursor to other synthetic compounds. Structurally, it is an ether (−O−) with a methyl (−CH3) and phenyl (−C6H5) group attached. Anisole is a standard reagent of both practical and pedagogical value. [2]

Contents

Reactivity

Anisole undergoes electrophilic aromatic substitution reaction at a faster speed than benzene, which in turn reacts more quickly than nitrobenzene. The methoxy group is an ortho/para directing group, which means that electrophilic substitution preferentially occurs at these three sites. The enhanced nucleophilicity of anisole vs. benzene reflects the influence of the methoxy group, which renders the ring more electron-rich. The methoxy group strongly affects the pi cloud of the ring as a mesomeric electron donor, more so than as an inductive electron withdrawing group despite the electronegativity of the oxygen. Stated more quantitatively, the Hammett constant for para-substitution of anisole is –0.27.

Illustrative of its nucleophilicity, anisole reacts with acetic anhydride to give 4-methoxyacetophenone:

CH3OC6H5 + (CH3CO)2O → CH3OC6H4C(O)CH3 + CH3CO2H

Unlike most acetophenones, but reflecting the influence of the methoxy group, methoxyacetophenone undergoes a second acetylation. Many related reactions have been demonstrated. For example, phosphorus pentasulfide (P4S10) converts anisole to Lawesson's reagent, [(CH3OC6H4)PS2]2. [3]

Also indicating an electron-rich ring, anisole readily forms π-complexes with metal carbonyls, e.g. Cr(η6-anisole)(CO)3. [4]

The ether linkage is highly stable, but the methyl group can be removed with strong acids, such as hydroiodic acid or boron trichloride: [5] :565–566

CH3OC6H5 + HIHOC6H5 + CH3I

Birch reduction of anisole gives 1-methoxycyclohexa-1,4-diene. [6]

Synthesis

Anisole was first synthesized in 1841 by Auguste Cahours by barium anisate decarboxylation while heating p-anisic acid he made earlier from the anise essence with barium oxide: [7] [8]

2 CH3OC6H4COOH + BaO → (CH3OC6H4COO)2Ba + H2O

(CH3OC6H4COO)2Ba → 2 CH3OC6H5 + BaCO3

It can be prepared by the Williamson ether synthesis from sodium phenoxide and dimethyl sulfate or methyl chloride: [9] [5]

2 C6H5O Na+ + (CH3O)2SO2 → 2 C6H5OCH3 + Na2SO4

Applications

Anisole is a precursor to perfumes, insect pheromones, and pharmaceuticals. [5] For example, synthetic anethole is prepared from anisole.

Safety

Anisole is relatively nontoxic with an LD50 of 3700 mg/kg in rats. [10] Its main hazard is its flammability. [10]

In the board game Scrabble , the word "anisole" is the 39th-most-likely word (out of over 25,000 possibilities) for a "bingo"/"bonus", i.e. the deployment of all seven letters in one's own hand simultaneously. [11]

See also

Related Research Articles

<span class="mw-page-title-main">Ether</span> Organic compounds made of alkyl/aryl groups bound to oxygen (R–O–R)

In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom bonded to two organyl groups. They have the general formula R−O−R′, where R and R′ represent the organyl groups. Ethers can again be classified into two varieties: if the organyl groups are the same on both sides of the oxygen atom, then it is a simple or symmetrical ether, whereas if they are different, the ethers are called mixed or unsymmetrical ethers. A typical example of the first group is the solvent and anaesthetic diethyl ether, commonly referred to simply as "ether". Ethers are common in organic chemistry and even more prevalent in biochemistry, as they are common linkages in carbohydrates and lignin.

<span class="mw-page-title-main">Ketone</span> Organic compounds of the form >C=O

In organic chemistry, a ketone is an organic compound with the structure R−C(=O)−R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group −C(=O)−. The simplest ketone is acetone, with the formula (CH3)2CO. Many ketones are of great importance in biology and industry. Examples include many sugars (ketoses), many steroids, and the solvent acetone.

Methylation, in the chemical sciences, is the addition of a methyl group on a substrate, or the substitution of an atom by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These terms are commonly used in chemistry, biochemistry, soil science, and biology.

Demethylation is the chemical process resulting in the removal of a methyl group (CH3) from a molecule. A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen atoms.

<span class="mw-page-title-main">Diazomethane</span> Simplest diazo compound and methylating agent

Diazomethane is an organic chemical compound with the formula CH2N2, discovered by German chemist Hans von Pechmann in 1894. It is the simplest diazo compound. In the pure form at room temperature, it is an extremely sensitive explosive yellow gas; thus, it is almost universally used as a solution in diethyl ether. The compound is a popular methylating agent in the laboratory, but it is too hazardous to be employed on an industrial scale without special precautions. Use of diazomethane has been significantly reduced by the introduction of the safer and equivalent reagent trimethylsilyldiazomethane.

<span class="mw-page-title-main">Methoxy group</span> Chemical group (–OCH3)

In organic chemistry, a methoxy group is the functional group consisting of a methyl group bound to oxygen. This alkoxy group has the formula R−O−CH3.

<span class="mw-page-title-main">Trimethylaluminium</span> Chemical compound

Trimethylaluminium is one of the simplest examples of an organoaluminium compound. Despite its name it has the formula Al2(CH3)6 (abbreviated as Al2Me6 or TMA), as it exists as a dimer. This colorless liquid is pyrophoric. It is an industrially important compound, closely related to triethylaluminium.

<span class="mw-page-title-main">Amidine</span> Organic compounds

Amidines are organic compounds with the functional group RC(NR)NR2, where the R groups can be the same or different. They are the imine derivatives of amides (RC(O)NR2). The simplest amidine is formamidine, HC(=NH)NH2.

The Ullmann condensation or Ullmann-type reaction is the copper-promoted conversion of aryl halides to aryl ethers, aryl thioethers, aryl nitriles, and aryl amines. These reactions are examples of cross-coupling reactions.

<span class="mw-page-title-main">Iron pentacarbonyl</span> Chemical compound

Iron pentacarbonyl, also known as iron carbonyl, is the compound with formula Fe(CO)5. Under standard conditions Fe(CO)5 is a free-flowing, straw-colored liquid with a pungent odour. Older samples appear darker. This compound is a common precursor to diverse iron compounds, including many that are useful in small scale organic synthesis.

<span class="mw-page-title-main">Lawesson's reagent</span> Chemical compound

Lawesson's reagent (LR) is a chemical compound used in organic synthesis as a thiation agent. Lawesson's reagent was first made popular by Sven-Olov Lawesson, who did not, however, invent it. Lawesson's reagent was first made in 1956 during a systematic study of the reactions of arenes with P4S10.

Tetrahydropyran (THP) is the organic compound consisting of a saturated six-membered ring containing five carbon atoms and one oxygen atom. It is named by reference to pyran, which contains two double bonds, and may be produced from it by adding four hydrogens. In 2013, its preferred IUPAC name was established as oxane. The compound is a colourless volatile liquid. Derivatives of tetrahydropyran are, however, more common. 2-Tetrahydropyranyl (THP-) ethers derived from the reaction of alcohols and 3,4-dihydropyran are commonly used as protecting groups in organic synthesis. Furthermore, a tetrahydropyran ring system, i.e., five carbon atoms and an oxygen, is the core of pyranose sugars, such as glucose.

<i>p</i>-Anisic acid Chemical compound

p-Anisic acid, also known as 4-methoxybenzoic acid or draconic acid, is one of the isomers of anisic acid. The term "anisic acid" often refers to this form specifically. It is a white crystalline solid which is insoluble in water, highly soluble in alcohols, and soluble in ether and ethyl acetate.

<i>tert</i>-Butyllithium Chemical compound

tert-Butyllithium is a chemical compound with the formula (CH3)3CLi. As an organolithium compound, it has applications in organic synthesis since it is a strong base, capable of deprotonating many carbon molecules, including benzene. tert-Butyllithium is available commercially as solutions in hydrocarbons (such as pentane); it is not usually prepared in the laboratory.

<span class="mw-page-title-main">4-Bromoanisole</span> Chemical compound

4-Bromoanisole is the organobromine compound with the formula CH3OC6H4Br. It is colorless liquid with a pleasant smell similar to that of anise seed. It is one of three isomers of bromoanisole, the others being 3-bromoanisole and 2-bromoanisole. It is the precursor to many 4-anisyl derivatives.

<span class="mw-page-title-main">2,6-Lutidine</span> Chemical compound

2,6-Lutidine is a natural heterocyclic aromatic organic compound with the formula (CH3)2C5H3N. It is one of several dimethyl-substituted derivative of pyridine, all of which are referred to as lutidines. It is a colorless liquid with mildly basic properties and a pungent, noxious odor.

<span class="mw-page-title-main">Bis(cyclooctadiene)nickel(0)</span> Chemical compound

Bis(cyclooctadiene)nickel(0) is the organonickel compound with the formula Ni(C8H12)2, also written Ni(cod)2. It is a diamagnetic coordination complex featuring tetrahedral nickel(0) bound to the alkene groups in two 1,5-cyclooctadiene ligands. This highly air-sensitive yellow solid is a common source of Ni(0) in chemical synthesis.

<span class="mw-page-title-main">Dichlorophenylphosphine</span> Chemical compound

Dichlorophenylphosphine is an organophosphorus compound with the formula C6H5PCl2. This colourless viscous liquid is commonly used in the synthesis of organophosphines.

Silylation is the introduction of one or more (usually) substituted silyl groups (R3Si) to a molecule. Silylations are core methods for production of organosilicon chemistry. Silanization involves similar methods but usually refers to attachment of silyl groups to solids.

<span class="mw-page-title-main">Hexamethylbenzene</span> Chemical compound

Hexamethylbenzene, also known as mellitene, is a hydrocarbon with the molecular formula C12H18 and the condensed structural formula C6(CH3)6. It is an aromatic compound and a derivative of benzene, where benzene's six hydrogen atoms have each been replaced by a methyl group. In 1929, Kathleen Lonsdale reported the crystal structure of hexamethylbenzene, demonstrating that the central ring is hexagonal and flat and thereby ending an ongoing debate about the physical parameters of the benzene system. This was a historically significant result, both for the field of X-ray crystallography and for understanding aromaticity.

References

  1. 1 2 3 Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. pp. 702–703. doi:10.1039/9781849733069-00648. ISBN   978-0-85404-182-4. Anisole, C6H5−O−CH3, is the only name in the class of ethers which is retained both as a preferred IUPAC name and for use in general nomenclature. For preferred IUPAC names, no substitution is allowed; for general nomenclature substitution is allowed on the ring and on the side chain under certain conditions (see P-34.1.1.4).
  2. Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York: Wiley-Interscience, ISBN   978-0-471-72091-1
  3. I. Thomsen; K. Clausen; S. Scheibye; S.-O. Lawesson (1984). "Thiation with 2,4-Bis(4-Methoxyphenyl)-1,3,2,4-Dithiadiphosphetane 2,4-Disulfide: N-Methylthiopyrrolidone". Organic Syntheses. 62: 158. doi:10.15227/orgsyn.062.0158.
  4. E. Peter Kündig (2004). "Synthesis of Transition Metal η6-Arene Complexes". Topics Organomet Chem. Topics in Organometallic Chemistry. 7: 3–20. doi:10.1007/b94489. ISBN   978-3-540-01604-5.
  5. 1 2 3 Helmut Fiege; Heinz-Werner Voges; Toshikazu Hamamoto; Sumio Umemura; Tadao Iwata; Hisaya Miki; Yasuhiro Fujita; Hans-Josef Buysch; Dorothea Garbe; Wilfried Paulus. "Phenol Derivatives". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a19_313. ISBN   978-3527306732.
  6. A. J. Birch and K. B. Chamberlain (1977). "Tricarbonyl[(2,3,4,5-η)-2,4-Cyclohexadien-1-one]Iron and Tricarbonyl[(1,2,3,4,5-η)-2-Methoxy-2,4-Cyclohexadien-1-yl]Iron(1+) Hexafluorophosphate(1−) from Anisole". Organic Syntheses. 57: 107. doi:10.15227/orgsyn.057.0107.
  7. Wisniak, Jaime (2013-10-01). "Auguste André Thomas Cahours". Educación Química. 24 (4): 451–460. doi: 10.1016/S0187-893X(13)72500-X . ISSN   0187-893X.
  8. Crochard (París); Arago, François; Gay-Lussac, Joseph Louis (1841). Annales de chimie et de physique (in French). Chez Crochard.
  9. G. S. Hiers and F. D. Hager (1929). "Anisole". Organic Syntheses . 9: 12. doi:10.15227/orgsyn.009.0012 .
  10. 1 2 MSDS Archived July 1, 2010, at the Wayback Machine
  11. "Fun with analytics: Probabilities and Scrabble". www.illumine8.com. Retrieved 2023-12-08.