Chloromethyl methyl ether alkylation

Alkylation. Ben2otrifluoride can also be alkylated, eg, chloromethyl methyl ether—chlorosulfonic acid forms 3-(trifluoromethyl)ben2yl chloride [705-29-3] (303,304), which can also be made from / -xylene by a chlorination—fluorination sequence (305). Exchange cyanation of this product in the presence of phase-transfer catalysts gives 3-(trifluoromethylphenyl)acetonitrile [2338-76-3] (304,305), a key intermediate to the herbicides flurtamone... 

The title compound has also been prepared by alkylations of (tributylstannyl)methanol with chloromethyl methyl ether (55% overall yield from paraformaldehyde) Sawyer, J. S. Kucerovy, A. Macdonald, T, L. McGarvey, G. J. J. Am. Chem. Soc. 1988, 110, 842. 

Methoxymethylation of alcohols is generally achieved through alkylation with chloromethyl methyl ether. The procedure described here for the preparation of Bu3SnCH20CH20CH3 avoids the use of the highly toxic chloromethyl ether by employing an acid-catalyzed acetal exchange reaction with dimethoxymethane for the... 

The latter was alkylated with chloromethyl methyl ether in the presence of triethylamine (89EUP315827). Aminomethylenemalonate... 

Chloromethyl methyl ether is an alkylating agent and very poisonous.Therefore this synthesis must be carried out with rubber gloves under a hood, preferentially in a glove box. 

I S-Cycloalkanediones.1 In the presence of a zinc reagent prepared from Zn-Cu and this alkyl iodide, chloromethyl methyl ether reacts with 1,2-bis(trimethyl-silyloxy)cycloalkenes (I) to form 2-hydroxy-2-methoxymcthylcycloalkanones (2) (cf 8, 415). Ring-enlarged 1,3-cycloalkanediones (3) are formed from (2) by treatment with acid. 

Chloromethyl methyl ether and bis-chloromethyl ether (CICH2 OCH2Cl) in common with several alkylating agents possess carcinogenic properties in experimental animals and have been listed as assumed human carcinogens similar hazardous properties associated with dichloromethyl methyl ether have not been reported but it would be prudent to handle this compound with due care. 

Based on these reactivities various derivatives of carbenes, such as the aminocarbene 238, are prepared by displacement of the OR group in 237 with amine via addition elimination, analogous to transesterification [74,75], As an example the carbanion 240, generated by deprotonation of 239, attacks ethylene oxide to give the lactone equivalent 241, which is further alkylated by chloromethyl methyl ether, again at the -position. Finally the oc-methylene-y-lactone 242 is obtained by oxidative demetallation with a Ce(TV) salt [76],... 

Examples of benzylic alkylation, aromatic ring deprotonation, and nucleophilic addition to a -position were used in a synthesis of (+)-20-methoxy-serrulat-14-en-7,8-diol. Deprotonation of the optically active complex (54) followed by reaction with chloromethyl methyl ether affords (55)... 

Certain diethers of the type ROCHaCH OR have been prepared by adding alkyl halides to a solution of sodium in excess ethylene glycol monoalkyl ether, as in the preparation of ethylene glycol dimethyl ether (78%). Chloromethyl methyl ether and alcohols react to give an acetal derivative of formaldehyde, CHjOCHjOR the reaction is carried out in the presence of pyridine. Aromatic diethers such as 2-methoxydiphenyl ether have been prepared by the Ullmann procedure. ... 

Melhoxymethylatwu off-kelo esters The sodium salts of fi-kcto esters on alkylation with chloromethyl methyl ether in HMPT give almost exclusively the product of O-alkylation (96-100%). Yields of O-alkylated products arc lower in less polar aprotic solvents. These enol ethers are reduced with lithium in liquid ammonia to the corresponding saturated esters (23-61 % yield). The method is most efficient for reduction of a relatively hindered keto group of a jS-keto ester. 

The kgjko isotope effect for the solvolysis of chloromethyl methyl ether in isopropyl alcohol at 0° is 1.24 + 0.08 per deuterium atom " . This is in the range of other unimolecular reactions. The values of and AS for the chloroether in isopropyl alcohol are 10.7 0.6 kcal.mole" and —28.8 + 1.6 eu, respectively. In contrast, the corresponding values for solvolysis of alkyl chlorides are in the range of about 20-25 kcal.mole and —4 to —12 eu. The lower values of A/f and AS for the solvolysis of chloromethyl methyl ether are tentatively attributed to the double bond character between oxygen and carbon at the transition state (see above) . 

The reaction of chloromethyl methyl ether (MOM-Cl, a carcinogen) with an alkoxide or with an alcohol in the presence of /-Pr2NEt (Hiinig s base) furnishes the corresponding formaldehyde acetal. Alkylation of 3°-alcohols requires the more reactive MOM-I, derived from MOM-Cl and Nal in the presence of /-ProNEt. ... 

Appropriate alkyl iodides or bromides were reacted with 57 and 2-epi-Sl in the presence of Ag20 in CH3CN with yields ranging from 36 to 77% (74, Scheme 10) [34, 51]. However, with these conditions preparation of branched alkyl ethers was unsuccessful [51]. Reacting 57 with chloromethyl methyl ether, diisopropylethy-lamine, and catalytic DMAP in CH2CI2 afforded 75 in a 72% yield and was the first 1 derivative reported to have increased affinity at the KOP receptor relative to 1. [41, 52]. Based on the successful increase in affinity of derivative 75, additional simple alkoxymethyl ethers were obtained using appropriate alkyoxymethyl chloride with diisopropylethylamine in DMF (76-78). However, more complex alkoxymethyl derivatives were synthesized from the common methylthiomethyl ether intermediate (79), which was obtained from reaction of 57 with acetic acid, acetic anhydride, and dimethylsulfoxide (DMSO) [52]. Compound 79 was then... 

More recently, Yamamoto and coworkers [36] have developed a new acyl anion equivalent based upon the ethoxyethyl-protected a-hydroxymalonodini-trile derivative shown in Scheme 13 and have applied it in the area of N-sulfonyl imine chemistry. Thus, the carbanion derived from the dinitrile was added to imine 60 to afford adduct 61 which was rather unstable. However, N-alkylation of 61 with chloromethyl methyl ether yielded the stable product 62. Removal of... 

Cyclohexadienones can be considered structurally as hemi-quinones and they have been synthesised in recent years by a variety of simple approaches in which invariably a substituent becomes attached to the 2- or 4- position and the structure becomes locked. 2,6-Dimethylphenol in hexane or benzene converted at 0°C to the anion with n-butyllithium in hexane, gradually warmed to ambient temperature, stirred for 1 hour, and then alkylated at 0 C with chloromethyl methyl ether afforded after 2-4 hours reaction 2,6-dimethyl-... 

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