Alkylation of alkenes, alkynes and Ar
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(1) Chloromethylation of benzene and toluene.
Kinetics and spectroscopy of the chloromethylation of benzene and toluene with chloromethyl methyl ether and AlCl3 in nitromethane or SnCl4 in dichloromethane have been studied.[DeHaan, 1997]
See also: [Yan, 2002], [Zimmermann, 2002]
Chloromethyl-(2-phenyl)ethyl ether cyclizes spontaneously to isochromane in more than 90 % yield. Other isochromane have been prepared in a similar way.[Untherhalt, 1996]
(3) Addition of allyl chloromethyl to methyl pirilate.
TiCl4 addition of allyl chloromethyl ether to methyl pirillate 1 gave the compound 2 with could be transformed into (+)-sirenin.[Preez, 1980]
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(4) Addition of chloromethylmethallyl ether to isoprene.
Electrophilic addition of chloromethyl methallyl ether to isoprene, followed by a Wittig rearrangement resulted in the formation of a C4-oxygenated acyclic terpenoid.[Garbers, 1976]
(5) Alkylation of ferrocene by chloromethyl methyl ether.
The alkylation of ferrocene by chloromethyl methyl ether in the presence of aluminum chloride and sodium borohydride occurs both at position 1 and at positions 1, 1'. Under the reaction conditions the initial alkylation products (methoxymethyl derivatives of ferrocene) are converted into chloromethyl derivatives and are partly reduced by sodium borohydride to 1-methyl- and 1,1'-dimethylferrocenes.[Tverdokhlebov, 1980]
(6) Chloromethylation of 5-nitrosalicylaldedhyde.
Chloromethylation of 5-nitrosalicylaldehyde can be accomplished in 90 % yield by employing 4 equivalents of aluminum chloride (one for each oxygen atom) plus a 10 % catalytic excess and by carrying out the reaction in pure chloromethyl methyl ether.[Taylor, 1963]
See also: [Hirano, 2002]
(7) Addition of chloromethyl methyl ether to trialkylalkenylsilanes.
1-Methoxy-2-propene and hexamethyldisiloxane were isolated in the reaction of TMSsilane and chloromethyl methyl ether in the presence of ZnCl2.[Shikhmamedbekova, 1970]
(8) Chloromethylation of 1,2-diphenylethanes.
Chloromethylation of 1,2-diphenylethanes with chloromethyl methyl ether and TiCl4, gave substituted dibenzo[a,d]cycloheptenes.[Yamato, 1997]
(9) Addition of chloromethyl ethers to 1-methoxy-2-methylprop-1-ene.
The addition of chloromethyl ethers to 1-methoxy-2-methylprop-1-ene is catalyzed by HgCl2. Hydrolysis of the resulting chloroethers gives 3-alkoxy-2,2-dialkylpropanals.[McCrindle, 1981]
(10) Coupling of ribofuranosyl fluoride and indoles.
The coupling reaction of a D-ribofuranosyl fluoride with indoles in the presence of boron trifluoride gives the corresponding C-nucleosides in a stereoselective manner depending upon reaction temperatures and solvents: the b-anomer is preferred under such conditions as - 15 to - 40 o C in nitroethane while the a-anomer is preferred at - 78 o C in propiononitrile.[Yokoyama, 1996]
(11) Formation of benzo- and naphtho-dihydrofuran derivatives.
Benzo- and naphtho-dihydrofuran derivatives were obtained by the reaction of glycosyl fluorides with phenol and naphthol derivatives in the presence of Cp2MCl2(AgOTf ( M = Hf, Zr). This process includes a glycosylation, an 1,2-migration and an intramolecular cyclization.[Matheu, 1996]
(12) Chloromethylation in the presence of KF
Perfluoro-2-methyl-2-pentene was successfully converted to perfluoro-(1,1-dimethylbutyl)methyl ethers by vic-oxymethyl fluorination with chloromethyl ethers in the presence of KF in aprotic polar solvents such as DMF and N-methyl pyrrolidone.[Ikeda, 1994]
(13) Halomethyl octyl ethers: Convenient halomethylation reagents
BCME-free halomethyl octyl ethers have been used in halomethylation of aromatic substrates.[Warshawsky, 1984]
(14) Chloromethyl ethers in the hydroxymethylation of olefines
Allyl chloromethyl ether and benzyl chloromethyl ether add to olefines. Subsequent cleavage of the resulting allyl and benzyl ethers result in hydroxymethylated olefines.[Garbers, 1975]
(15) Chloromethylation of thiophenes
2,5-Bis(chloromethyl)thiophene was prepared by reaction of thiophene with chloromethyl methyl ether in a mixture of phosphoric acid and acetic acid. [Takeshita, 1991]
The 2,4-bis(chloromethyl)-3,5-dibromothiophene 2 can be prepared by chloromethylation of 2,4-dibromothiophene. Interestingly, compound 2 can also be prepared by chloromethylation of 2,5-dibromothiophene 1.[Takeshita, 1992]
See also: [Liu, 2002]
(16) Lewis acid catalyzed addition reactions of a-chloroalkyl ethers to carbon-carbon double bonds.
The Friedel-Crafts alkylation of aromatic compounds is a reaction of very broad scope.[Roberts, 1984] The corresponding reaction with alkenes seems to be of more limited value, because Lewis acid polymerization of the alkene is often observed with simple alkyl halides.[Kennedy, 1982] With reactive alkyl halides like a-monohalo ethers, however, good yields of 1:1 addition products with alkenes can be obtained. 2-Methylpropene 1 adds for instance the a-chloro ether 2 to give the 1:1 adduct 3 in an excellent yield.[Mayr, 1983]
(17) Alkylation of ferrocenyl alkenes
In the alkylation of simple alkenes the intermediate carbocations cannot be isolated, but are trapped in situ by the halogenide. In the ferrocenyl alkenes, however, the initially formed carbocation is in many cases stable and can be reacted with a nucleophile in a subsequent step.[Ketter, 1990] Reaction of the ferrocenyl alkenes 2-4 with the a-chloro ether 5 or 6 gave the corresponding cations, which was trapped by LiN3 to give the addition compounds 7-8. The Lewis acid used is very important for a clean reaction and the acid of choice is TiCl2(Oi-Pr)2. The reaction is not without limitations; for instance vinylferrocene 1 does not give a monomeric product.
The stereochemical course of the this reaction involves "exo" attack of the a-chloro ether at the b-carbon of the double bond relative to the ferrocene, and subsequent "exo" attack of the nucleophile at the carbocationic center formed in the first step.
(18) Friedel-Crafts type alkylation of an iron complex of cyclooctatriene.
Reaction of 1 with an excess methoxymethyl chloride in the presence of AlCl3 gave the cationic complex 2, which furnished the 1,4-cis-disubstituted diene complex 3 in the reaction with dimethyl sodiomalonate.[Pearson, 1992]
In the reaction of a-halo ethers with dienes weak Lewis acid like ZnCl2 give a mixture of 1,2-addition and 1,4-addition. When stronger Lewis acids as SnCl4 are used, only 1,4-addition is observed.[Mayr, 1983]
a-Halo ethers also react with acetylenes in the presence of a Lewis acid catalyst to give 1:1 adducts.[Gross, 1967], [Marcuzzi, 1987] Reaction of acetylene itself with methoxymethyl chloride in the presence of AlCl3, gave the 1:1 adduct 1 in 60 % yield. [Jäger, 1977] If AlBr3 is used as catalyst, the halogen atom from the a-halo ether as well as a halogen atom from the catalyst can be added to the acetylene.[Bindácz, 1960]
(21) Addition of ethoxymethyl chloride to phenyl substituted alkenes.
ZnCl2 catalyzed addition of ethoxymethyl chloride to some phenyl substituted alkynes afforded mixtures of the ethoxymethylated addition product and the chloromethylated addition product.[Marcuzzi, 1987]
(22) Chloromethylation of deactivated aromatic compounds.
Chloromethylation of deactivated aromatic compounds under standard conditions i.e. formaldehyde and hydrochloric acid in the presence of a Lewis acid, gives mainly unchanged starting materials. [Suzuki, 1970] Using an excess of methoxymethyl chloride and 60 % fuming sulfuric acid, however, deactivated aromatic compounds can be chloromethylated. 23-Nitro-2,4,6-trimethylbenzyl chloride 1 was thus obtained in 75 % yield.
(23) Bromomethylation of aromatic compounds
Bromomethylation of aromatic compounds can be done with methoxymethyl bromide.[Vavon, 1939] Zinc bromide was used as a catalyst in the mono-bromomethylation of a number of aromatic compounds.[Olah,1974] If di-bromomethylation is wanted, aluminium chloride seems to be the preferred Lewis acid catalyst.[Kundu,1982]
(24) Iodomethylation of aromatic compounds
Iodomethylation of aromatic compounds has been carried out using either methoxymethyl chloride and hydroiodic acid, [Sandin, 1940] or pure methoxymethyl iodide.[Rogozhin, 1966] Methoxymethyl iodide is conveniently prepared by treatment of dimethoxymethane with TMSI at room temperature.[Jung, 1978] Other iodomethyl ethers have been prepared by the same method.
(25) Friedel-Crafts alkylation wiht glycosyl halides
In a Friedel-Crafts approach to C-aryl glycosides, a number of glycosyl halides have been reacted with aromatic compounds.[Jaramillo, 1994] When strong Lewis acids like AlCl3 are used as catalyst, low yields are obtained due to side reactions.[Hurd, 1945] With activated aromatic compounds like 1, milder Lewis acids can be used, giving good yields of C-aryl glycosides.[Eade, 1979] The reaction is stereoselective, giving only the b-isomer 2.
(26) Reaction of vinylsilanes with chlorometyl methyl ether
Trans 1,2-Bis(trimethylsilyl)ethene reacts with chloromethyl methyl ether in the presence of aluminum chloride to give the corresponding trans propene 1.[Pillot, 1975]
(27) Electrophilic accition of a-fluoroalkyl ethers to olefins
a-Fluoro ethers enter into electrophilic addition with methylenecyclobutane, cyclohexene, cyclopentene and 1-hexene at room temperature in the absence of catalysts. [Lebedev, 1989]
(28) Chloromethylation of 3-iodoanisole
When the 3-iodoanisole is reacted with chloro(methoxy)methane at room temperature for four days, the bis-chloromethylated product is obtained in 68% yield .[Kuroda, 2000]
(29) Chloromethylation of an allylsilane
The allylsilane reacted cleanly with chloro(methoxy)methane using stannic chloride as Lewis acid. Other Lewis acids, such as aluminium chloride, boron trifluoride and titanium tetrachloride gave inferior yields and mixtures of unidentified products. [Fleming, 1981]
(30) Synthesis of homoallyl ethers
Iodotrimethylsilane and trimethylsilyl triflate activate selectively the C-Cl bond rather than the C-O bond in a-chloro ethers and catalyze the allylation with allylsilane to give the corresponding homoallyl ethers in good yields. [Sakurai, 1983]
(31) Chloromethylation of tribenzotriquinacenes [Zhou, 2007]
(32) Choromethylation of thiophenes II. [Hossain, 2005]
(33) Synthesis of propargylic methyl ethers
The treatment of propargylic alcohols with n-BuLi and MOMCl afforded the corresponding propargylic methyl ethers.[Li, 2009]
