Ethers alkyl chloromethyl

The above explains the key roles of (a) the nucleophilicity of the nucleophile (b) the substituent(s) (c) the polarity of the reaction medium and (d) the the bulkiness of the nucleophile, in determining the regio- and stereo-specificity of the reaction. The reaction of alkyl chloromethyl ethers with thiirane oxides to give sulfenic esters128 appears to be mechanistically analogous. 

A mechanism analogous in many ways to that of the acid-catalyzed ring opening reaction was advanced for the reaction of the thiirane oxide with alkyl chloromethyl ethers S . The first step is the displacement of the chloride by the sulfoxy oxygen (equation 24). In view of the above mechanistic interpretation, it is quite surprising that the parent thiirane oxide (16a) was found to be protonated on sulfur and not at oxygen in FSOjH-SbFfi at — 78 °C, according to NMR studies s . 

Caution. The sodium tetrahydroborate should be added slowly to prevent foaming of the reaction mixture from the reaction vessel. Alkyl chloromethyl ethers are potent carcinogens13 and should be handled and disposed of with appropriate precautions. 

Hydroxymethylation of carbonyl compounds.3 Alkyl chloromethyl ethers react in the presence of Sml2 (2 equiv.) with ketones in THF to give adducts in 50-80% yield. The reaction with aldehydes is conducted in tetraethylene glycol dimethyl ether, which suppresses pinacol reduction. Hydroxymethylation of carbonyl compounds can be effected by use of benzyl chloromethyl ether followed by hydrogenolysis of the adduct. 

A number of other miscellaneous systems that bear some relationship to Reissert compounds have also been reported but will not be covered in depth here. Thus, for example, the reaction of isoquinoline, potassium cyanide, and alkyl chloromethyl ethers give 116. A similar compound was also prepared from quinoline. Compounds of type 117 have been reported to undergo rearrangements similar to Reissert compounds. A... 

An interesting, different type of Grignard compound, the (alkoxymethyl)-magnesium chlorides, can be obtained from alkyl chloromethyl ethers. These products decompose very easily thus ... 

Alkyl chloromethyl ethers react with thiiran 1-oxide to give sulphenic esters (26), probably by way of an intermediate sulphoxonium salt (27). Thiiran oxide in FSOsH-SbF at — 78 C was protonated at sulphur and not at oxygen, according to n.m.r. studies. ... 

The hydroxyl groups can be alkylated in the usual manner. Hydroxyalkyl ethers may be prepared with alkylene oxides and chloromethyl ethers by reaction with formaldehyde and hydrogen chloride (86). The terminal chlorides can be easily converted to additional ether groups. 

Alkylation involving formaldehyde in the presence of hydrogen chloride is known as chloromethylation (eq. 3). The reagent may be a mixture of formalin and hydrochloric acid, paraformaldehyde and hydrochloric acid, a chloromethyl ether, or a formal. Zinc chloride is commonly employed as a catalyst, although many other Lewis acids can be used. Chloromethylation of sahcyhc acids yields primarily the 5-substituted product 5-chlotomethylsahcyhc acid [10192-87-7] (4). 

Etherification. The reaction of alkyl haUdes with sugar polyols in the presence of aqueous alkaline reagents generally results in partial etherification. Thus, a tetraaHyl ether is formed on reaction of D-mannitol with aHyl bromide in the presence of 20% sodium hydroxide at 75°C (124). Treatment of this partial ether with metallic sodium to form an alcoholate, followed by reaction with additional aHyl bromide, leads to hexaaHyl D-mannitol (125). Complete methylation of D-mannitol occurs, however, by the action of dimethyl sulfate and sodium hydroxide (126). A mixture of tetra- and pentabutyloxymethyl ethers of D-mannitol results from the action of butyl chloromethyl ether (127). Completely substituted trimethylsilyl derivatives of polyols, distillable in vacuo, are prepared by interaction with trim ethyl chi oro s il an e in the presence of pyridine (128). Hexavinylmannitol is obtained from D-mannitol and acetylene at 25.31 MPa (250 atm) and 160°C (129). 

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... 

Several other alkylation reactions of benzyl chloromethyl ether have been reported using phosphorus compounds as nucleophiles. Hydrolysis and alcoholysis reactions of the reagent have been investigated along with the addition of the chloroether to propylene in the presence of zinc chloride. The alkylation of enamines with benzyl bromomethyl ether has been reported. ... 

Alkylation, of acids, 50,61 with benzyl chloromethyl ether, 52,... 

Small samples may readily be distilled with little decomposition, while large samples decompose significantly during (list, nation. The undistilled material may be satisfactory for use in alkylation reactions without purification. The checkers have (bund that 200 g. quantities of the product can reprodticibly lie distilled at approximately 1 mm. The reported physical constants for benzyl chloromethyl ether are b.p. 96-98° (9.5 imn.)2, n n 1.5264-1.5292. i2... 

More recently Franck et a/.331 prepared the pyrrolo[l,2-a]indolyl anion (247) by a similar method as part of a total synthesis of the mitomycin antibiotics (Section VI,A) Alkylation of (247) with methyl chloromethyl ether followed by photooxidation gave a product 248 with the basic mitomycin skeleton. 

Alkyl chloroformates, R0C(=0)C1, might be expected to hydrolyse rapidly by an SNl-type process, reminiscent of the hydrolysis of alkoxy ethers such as chloromethyl ether. Similarly, carbamates would be expected to react by a similar mechanism because of the possible stabilisation of the acylium ion formed, viz. 

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. 

Alkyl ethers of sucrose have been prepared by reaction with long-chain alkyl halides to provide mixtures of regioisomers and products of different degree of substitution.82,83 A similar reaction with chloromethyl ethers of fatty alcohols provides formaldehyde acetals.84,85 Alkenyl ethers of various carbohydrates, and notably of sucrose, can also be obtained by palladium-catalyzed telomerization of butadiene (Scheme 6).86 88 Despite a low-selectivity control, this simple and clean alternative to other reactions can be carried out in aqueous medium when sulfonated phosphines are used as water-soluble ligands. 

The generation of ion pairs from NH-unsubstituted tetrazoles has also been performed using sodium salts and sodium hydroxide. Tetrazole alkylation with benzyl chloromethyl ether in tetrahydrofuran (THF) in the presence of sodium hexamethyldisilazane (NaHMDS) has been reported < 1995J(P 1) 1747, 1998SL528>. Regioisomers 240 and 241 formed under these conditions in comparable amounts (Scheme 24) <1998SL528>. 

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