ANISOLE

Anisole = Methoxybenzene

CAS Number: 100-66-3 
IUPAC Name: Anisole
EC Number: 202-876-1
Molecular Formula: C7H8O
Molecular Weight: 108.14 g/mol

Description:
Anisole is a flavouring agent.
Anisole is a precursor to perfumes, insect pheromones, and pharmaceuticals. 
For example, synthetic anethole is prepared from anisole. 
Anisole undergoes electrophilic aromatic substitution reaction more quickly than does 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, moreso than the inductive effect of the electronegative oxygen.
Anisole is a colorless to yellowish liquid with an agreeable, aromatic, spicy-sweet odor.
Anisole has a characteristic pleasant, anise-like, agreeable aromatic odor.
Anisole is used in perfumery.
Anisole, or methoxybenzene, is an organic compound with the formula CH3OC6H5. 
Anisole 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. 
Anisole is mainly made synthetically and is a precursor to other synthetic compounds. 
Anisole is an ether. 
Anisole is a standard reagent of both practical and pedagogical value.
Anisole can be prepared by the Williamson ether synthesis; sodium phenoxide is reacted with a methyl halide to yield anisole.
Anisole is a monomethoxybenzene that is benzene substituted by a methoxy group. 
Anisole has a role as a plant metabolite.
Anisole can also convert to o-cresol as a relatively slow monomolecular rearrangement reaction in which the alkyl group transfers from the O site to the (2) position on the aromatic ring.
Anisole is a starting raw material to be chemically transformed by Pharmaceuticals Industries (technical grade). 
Anisole's appearance is a clear liquid. 
Anisole presents a wide range of applications: solvent for chemical reactions, synthesis intermediates and solvent for electronics.
Anisole, or methoxybenzene, is an organic compound with the formula CH3OC6H5. 
Anisole 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. 
Anisole is mainly made synthetically and is a precursor to other synthetic compounds.
Anisole, also known as anise ether, methoxybenzene methyl phenyl ether, is a colorless liquid with an odor of anise, sweet, naturally present in the tarragon oil.
Anisole is insoluble in water, soluble in alcohol, ether, acetone, soluble in benzene. 
Anisole is obtained originally from distilled methyl salicylate or methoxybenzoate, is now mainly produced through the reaction of methylating agent of dimethyl sulfate with phenol in alkaline aqueous solution. 
Anisole is prone to start Electrophilic substitution reaction in aromatic nucleus, and condensed with formaldehyde to produce viscous oil or resin material.
Anisole reacts with phosphorus trichloride to produce chlorine anisole and a small amount of o-chloro product, reacts with thionyl chloride to produce 2,4,6-trichloroanisole. 
Anisole is heated to react with hydrobromic or hydroiodic, carbon-oxygen bond cleaves, phenol and halogenated methane is produced, which is an important method for determining methoxy group of benzene ring.
A colorless liquid ether C6H5OCH3 of pleasant odor obtained by distilling anisic acid or by the action of dimethyl sulfate and alkali on phenol.
And used chiefly in perfumery; methyl phenyl ether.
If the substrate is a very reactive benzene derivative, such as anisole, carboxylic esters or acids may be the source of the acylating electrophile.
A common characteristic of the halogenation, nitration, sulfonation and acylation reactions is that they introduce a deactivating substituent on the benzene ring.
Anisole, also known as anise ether, methoxybenzene methyl phenyl ether.
Anisole is a colorless liquid with an odor of anise, sweet, naturally present in the tarragon oil.
Anisole is insoluble in water, soluble in alcohol, ether, acetone.
Anisole is soluble in benzene.
Anisole is a reactive aromatic substrate and undergoes Friedel–Crafts acylations under a diverse range of conditions to give p-ketone(the o-isomer is sometimes observed, e.g., <83CB1195>).
The remaining dichloromethane layer now only contains the neutral compound anisole.
Anisole, also known as anise ether, methoxybenzene methyl phenyl ether, is a colorless liquid with an odor of anise.
Anisole is sweet, naturally present in the tarragon oil.
Anisole is insoluble in water, soluble in alcohol, ether, acetone, soluble in benzene.

Uses of Anisole:
Anisole is used in the production of perfumes, dyes, drugs, pesticides and as solvents.
Anisole can be used as analytical reagents, solvents, perfumes and pesticide preparations.
Anisole is used as a spice for food. 
Anisole is mainly used to prepare vanilla, fennel and beer flavors.
Anisole is used in organic synthesis, solvent, perfume and insect repellent.
Anisole is used as recrystallization solvent, constant temperature filler, refractive index, perfume, organic synthesis intermediate.
Anisole is widely used as a solvent for the synthesis of various organic compounds, anethole, nonylphenol isomer 4-(3',6'-dimethyl-3-heptyl)phenol, perfumes, insect pheromones and pharmaceuticals. 
Anisole finds application in the preparation of inorganic complexes and materials such as tin-core/tin oxide nanoparticles.
Anisole is used in perfumery, in organic syntheses.
Anisole is a biochemical for proteomics research.
Anisole is mainly used for the preparation of vanilla, fennel and beer flavor.
Anisole is used for analyzing the reagents, solvents, and used for preparing perfumery and enteral pesticides.
Anisole is used for the production of perfumes, dyes, pharmaceuticals, pesticides, also used as a solvent.
Anisole is used in organic synthesis, also used as solvents, perfume and insect repellent.
Anisole is used as solvents for recrystallization, fillers of thermostat, and used for measuring refractive index, as spices and organic synthesis intermediates.
Anisole is a precursor to perfumes, insect pheromones, and pharmaceuticals.
For example, synthetic anethole is prepared from anisole.
Anisole is a starting raw material to be chemically transformed by Pharmaceuticals Industries (technical grade). 
The appearance of anisole is a clear liquid. 
Anisole presents a wide range of applications: solvent for chemical reactions, synthesis intermediates and solvent for electronics.
Anisole is used to make perfumes, flavorings and as a solvent. 
Anisole is a flavouring agent Anisole is a precursor to perfumes, insect pheromones, and pharmaceuticals. For example, synthetic anethole is prepared from anisole.

Reactivity Profile  and Reactions of Anisole:
Anisole is produced through the reaction of methylating agent of dimethyl sulfate with phenol in alkaline aqueous solution. 
Phenol was mixed with sodium hydroxide solution, dimethyl sulfate was slowly added at below 10 ℃. 
And then heat to 40 ℃, reflux for 18h, then stand for separation of the oil and dried with anhydrous calcium chloride, vacuum distillation to obtain anisole.
Anisole is derived by introducing the methyl chloride into the sodium phenol of liquid ammonia to react.
Anisole is generated from heating phenol and methanol.
By reacting phenol and dimethyl sulfate in the presence of aqueous NaOH; by passing methyl chloride into a suspension of sodium phenolate in liquid ammonia.
Anisole is prepared by methyl
ation of sodium phenoxide with dimethyl sulfate or methyl chloride:
2 C6H5O−Na+ + (CH3O)2SO2 → 2 C6H5OCH3 + Na2SO4
Anisole can be prepared from phenol or its salts by the use of the following methylating agents: 
-methyl chloride
-sodium methyl sulfate
-methyl alcohol in the presence of thorium oxide
-methyl alcohol
-β-naphthalenesulfonic acid
-potassium hydrogen sulfate
-boron fluoride
-dimethyl sulfate and methyl
Mixture of Phenol and Sodium Hydroxide is dissolved in cold-water bath with continuous stirring.
To this mixture (still kept in cold water bath), Dimethyl Sulfate is added and it is kept in water bath for 60 minutes.
Mixture is heated for 30 minutes.
Anisole can be derived from benzene by replacing one of the hydrogen atoms with a methoxy group. 
Anisole has been reported that the log P of anisole is 2.11 and that of benzene is 2.13.
Phenol to anisole: First let us see the structures of phenol and anisole. 
In this what we need to do is replace the H atom from –OH group to CH3. 
This can be done by first reacting phenol with a base NaOH and then treating it with an alkyl halide like CH3−Br .
Ethers, such as Anisole can act as bases. 
Anisole forms salts with strong acids and addition complexes with Lewis acids. 
The complex between diethyl ether and boron trifluoride is an example. 
Anisole may reacts violently with strong oxidizing agents. 
In other reactions, which typically involve the breaking of the carbon-oxygen bond, ethers are relatively inert.
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, P4S10 converts anisole to Lawesson's reagent, [(CH3OC6H4)PS2]2.
Also indicating an electron-rich ring, anisole readily forms π-complexes with metal carbonyls, e.g. Cr(η6-anisole)(CO)3.
The ether linkage is highly stable, but the methyl group can be removed with hydroiodic acid:
CH3OC6H5 + HI → HOC6H5 + CH3I
Birch reduction of anisole gives 1-methoxycyclohexa-1,4-diene.
In anisole the resonace stabilisation from the lone pair of electrons on the oxygen atom is somewhat disturbed through a hyperconjugation. 
This effect is however absent in phenol and hence the aromatic ring is more electron rich thereby phenol is more reactive than anisole towards electrophilic aromatic substitution.
Anisole is less reactive than phenol towards electrophilic substitution reactions.
Anisole is because of this extra stability of structures, II-IV through loss of a proton which is responsible for greater reactivity of phenol over anisole.
Anisole is flammable. 
Ethers tend to form unstable peroxides when exposed to oxygen. 
Ethyl, isobutyl, ethyl tert-butyl, and ethyl tert-pentyl ether are particularly hazardous in this respect. 
Ether peroxides can sometimes be observed as clear crystals deposited on containers or along the surface of the liquid. 
Anisole is insoluble in water.
Shake anisole with half its volume of 2M NaOH, and the emulsion is allowed to separate. 
Repeat three times, then wash twice with water, dry over CaCl2, filter, dry over sodium wire.
Finally distil anisole from fresh sodium under N2 using a Dean-Stark trap (samples in the trap being rejected until free from turbidity).
Alternatively dry anise with CaSO4 or CaCl2, or by refluxing with sodium or BaO with crystalline FeSO4 or by passage through an alumina column. 
Traces of phenols are removed by prior shaking with 2M NaOH, followed by washing with water. 
Anisole has been be purified by zone refining. 

Storage and Handling of Anisole:
Store in a properly labeled and tightly closed container in a cool and well-ventilated area. 
Keep the container away from heat and other possible sources of ignition. 
Handle in accordance with good industrial hygiene and safety practices. 
Containers that are opened must be carefully resealed and kept upright to prevent leakage. 
Wear suitable protective clothing and personal protective equipment (PPE). 
In case of insufficient ventilation, wear suitable respiratory equipment. 
Avoid contact with skin and eyes. 

Chemical and Physical Properties:
ChEBI: CHEBI:16579
ChEMBL: ChEMBL278024 
ChemSpider: 7238 
ECHA InfoCard: 100.002.615 
Gmelin Reference    2964
KEGG: C01403 
PubChem CID: 7519
RTECS number: BZ8050000
UNII: B3W693GAZH 
UN number: 2222
CompTox Dashboard (EPA): DTXSID4041608     
XLogP3: 2.1    
Hydrogen Bond Donor Count: 0    
Hydrogen Bond Acceptor Count: 1    
Rotatable Bond Count: 1    
Exact Mass: 108.057514874    
Monoisotopic Mass    108.057514874    
Topological Polar Surface Area: 9.2 Ų    
Heavy Atom Count: 8    
Formal Charge: 0    
Complexity: 55.4    
Isotope Atom Count: 0    
Defined Atom Stereocenter Count: 0    
Undefined Atom Stereocenter Count: 0    
Defined Bond Stereocenter Count: 0    
Undefined Bond Stereocenter Count: 0    
Covalently-Bonded Unit Count: 1    
Compound Is Canonicalized: Yes

Synonyms:
Anisole
Methoxybenzene
100-66-3
Benzene, methoxy-
Methyl phenyl ether
Anisol
Phenyl methyl ether
Phenoxymethane
Anizol
Phenol methyl ether
Methoxy-Benzene
4-methoxybenzene
HSDB 44
UNII-B3W693GAZH
NSC 7920
Ether, methyl phenyl-
MFCD00008354
B3W693GAZH
CHEBI:16579
4-methoxy-benzene
Anisole, 99%, pure
Benzene, methoxy
Ether, methyl phenyl
FEMA Number 2097
Anisole, 99%, Extra Dry, AcroSeal(R)
FEMA No. 2097
EINECS 202-876-1
UN2222
Anisloe
anisole-
AI3-00042
methylphenyl ether
4-methoxy benzene
Anethole,(S)
Methyl phenyl-Ether
Anisole, 8CI
Anisole Methoxybenzene
Methoxy-Benzeneanisole
154492-88-3
Anisole-[13C]
PubChem12830
Methoxy-benzene (anisol)
bmse010217
EC 202-876-1
SCHEMBL1205
WLN: 1OR
Anisole, analytical standard
ACMC-1C6S9
Anisole, anhydrous, 99.7%
SCHEMBL497674
AQUALINE STANDARD 1.0
Aqualine&trade; Standard 1.1
CHEMBL278024
DTXSID4041608
SCHEMBL12015260
FEMA 2097
Anisole, ReagentPlus(R), 99%
NSC7920
METHOXY-BENZENE (ANISOL)
Anisole, >=99%, FCC, FG
LABOTEST-BB LTBB002265
ZINC897131
AMY38503
NSC-7920
ANW-14338
BDBM50386177
CE0043
EpiMediuM BreviconuM P.E.(Icariin)
STL263485
AKOS000120161
ZINC329788065
ZINC329788108
AS04310
CCG-266043
MCULE-2691526560
UN 2222
Anisole [UN2222] [Flammable liquid]
I767
LS-13275
DB-003588
A0492
FT-0628309
FT-0652964
FT-0662229
A14924
C01403
M03556
14387-EP2272822A1
14387-EP2316836A1
19606-EP2269986A1
19606-EP2269995A1
19606-EP2270000A1
19606-EP2272517A1
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19606-EP2308926A1
19606-EP2308960A1
19606-EP2309564A1
19606-EP2311827A1
19606-EP2314558A1
19606-EP2314576A1
19606-EP2314587A1
19606-EP2314590A1
19606-EP2314591A1
37374-EP2311802A1
37374-EP2311803A1
56738-EP2277868A1
56738-EP2277869A1
56738-EP2277870A1
56738-EP2292608A1
56738-EP2295422A2
56738-EP2298305A1
56738-EP2298746A1
56738-EP2298769A1
56738-EP2308878A2
56738-EP2371806A1
56738-EP2371807A1
56738-EP2380568A1
187286-EP2272849A1
Q312244
J-000194
F1908-0172
Anisole, United States Pharmacopeia (USP) Reference Standard
Anisole, Pharmaceutical Secondary Standard; Certified Reference Material