Dichloromethyl methyl ether preparation

Dichloromethyl methyl ether has been prepared by the chlorination of chlorodimethyl ether in the liquid5-4 or gas phase,5 by the reaction of chlorodimethyl ether with sulfuryl chloride and benzoyl peroxide,6 7 and by the treatment of methyl formate with phosphorus pentachloride.8-10... 

Dichloromethyl methyl ether may be employed preparatively in various ways. Thus it effects the replacement of carbonyl and hydroxyl oxygens by chlorine,11 and may be used in the preparation of a-acetochlorosugars 12 and acid chlorides, particularly those derived from acetylated monocarboxylic acid sugars 12 13... 

Dichloromethyl methyl ether, 47, 47 in preparation of aromatic aldehydes,... 

Several chlorophyll derivatives have been prepared by electrophilic substitution, inter alia by formylation reactions. Adopting methods from corrin chemistry.50 alkylation with chloro-methyl methyl ether (caution toxic),32k chloromethyl methyl sulfide,51 and dichloromethyl methyl ether (caution toxic)52 in the presence of Lewis acids are the methods of choice to introduce carbon residues into the chlorin frame work. The compounds listed below have been prepared by these methods. 

The base-induced reaction of dichloromethyl methyl ether with trialkyl- and triarylboranes also provides a powerful method for the preparation of the corresponding tertiary carbinols.1617 fn this case, all three groups transfer readily from horon to carbon under mild conditions, and oxidation with alkaline hydrogen peroxide provides the tertiary alcohol ... 

Alkyl- or aryl-dibenzothiophenes are conveniently prepared from the 2-arylthio-cyclohexanones, which are readily cyclized and dehydrogenated to yield the respective 1-, 2-, 3- or 4-substituted dibenzothiophenes (382 equation 9 Section 3.15.2.3.2). More complex polycyclic systems are available, using suitable aryenethiols, such as naph-thalenethiols, and 2-bromo-l-tetralone to synthesize the appropriate 2-arylthio ketones. Diaryl sulfides can be converted to dibenzothiophene derivatives in satisfactory yields by photolysis in the presence of iodine (equation 10) (75S532). Several alkyldibenzothiophenes with substituents in the 2- and/or 3-positions were prepared in satisfactory yield by the condensation of dichloromethyl methyl ether with substituted allylbenzo[6]thiophenes (equation 11) (74JCS(P1)1744). 

Treatment of diaryl ethers with dichloromethyl methyl ether in the presence of tin(lV) chloride leads to xanthylium salts (Scheme 268) (73JCS(Pl)ll04). It is necessary that the diaryl ether is so designed that electrophilic attack occurs ortho to the potential heteroatom. The thienopyrylium salts (673) and (674) have been prepared in the same manner. 

Minkwitz et al.604 have prepared the hexafluorometalates of cations 308. The reaction of a,a-dichloromethyl methyl ether in HF-Lewis acid solution at —78°C leads to the formation of chloro cation 308-C1, whereas at -65°C fluoro derivative 308-F is isolated as a result of chlorine-fluorine exchange [Eq. (3.80)]. Interestingly, the chlorine atom and the methyl group are trans in the hexafluoroantimonate salt of cation 308-C1, whereas the fluorine atom and the methyl group are cis in cation 308-F. The arrangement of the C—O—C—H atoms is nearly planar with F/Cl—C—O—C torsion angles of 2.84° (308-F) and 179.0° (308-C1). The C Obond distances (1.224 and 1.479 A for cation 308-F, and 1.252 and 1.517 A for cation 308-C1) reveal dominant oxonium ion character. 

The synthesis of dichloromethyl methyl ether has been included because of its usefulness as a reagent for the preparation of aromatic aldehydes (Expt 6.115). It is readily obtained by the reaction of phosphorus pentachloride in admixture with phosphorus oxychloride with methyl formate (Expt 5.71). 

Fully acetylated aldonyl chlorides have been prepared by treatment of acetylated aldonic acids with phosphorus pentachloride87 or thionyl chloride.88 Dichloromethyl methyl ether was later shown to afford the derivative of D-gluconic acid in almost quantitative yield.89... 

The preparation of 2-methoxy-l,3-dithiolane (292) is based on the reaction of dichloromethyl methyl ether with the disodium salt of ethanedithiol in acetonitrile (72HCA75). 

Formylation of unsaturated silanes. a, -Unsaturated aldehydes can be prepared by reaction of vinylsilanes with dichloromethyl methyl ether in the presence of 1 equiv. of TiCl, (equation 1). The enals have the (E)-conflguration, regardless of... 

Summary Methoxy-bis[tris(trimethylsilyl)silyl]methane (4), the first geminal di(hyper-silyl) compound with a central carbon atom, was prepared by the reaction of tris(tri-methylsilyl)silyl lithium with dichloromethyl methyl ether. The structure of 4, which is characterized by considerable distortions due to the spatial demand of the two (MesS aSi groups, is discussed on the basis of an X-ray crystal structure analysis. 

A method for converting carboxylic acids under neutral conditions to the corresponding acid chlorides is available with a-halogenated ethers as reagents. Thus it has been shown that 2-chlorodioxin can give acid chlorides of a variety of acids in good yield. The method, however, has not received wide application. Instead a,a-dichloromethyl methyl ether, which can be prepared easily, has replaced other a-ha-loethers as reagents. In Table 3 some examples are listed. 

Sometimes the addition of a small amount of ZnCh as a catalyst is recommended, e.g. succinic acid is transformed to the dichloride only in the presence of this catalyst. It has to be noticed, however, that under these conditions hydrogen chloride is evolved and, therefore, acid sensitive compounds cannot be taken. Af-acylamino acid chlorides and chlorides of fully acetylated sugar acids are also obtainable in yields of 70% or more. Whereas most reagents seem to be unsuited to the preparation of acid halides of a-keto acids, dichloromethyl methyl ether is successful in this reaction (equation 10). Pyruvyl chloride can now be made in ca. 50% yield. In some examples the corresponding a,a-dibromomethyl methyl ether has also been tested. ... 

If carboxylic acid esters are readily available, they provide a convenient basis for the preparation of acid halides. Modified phosphorus halides, like 2,2,2-trichloro-l,3,2-benzodioxaphosphole can be applied successfully. This reagent forms first a 1,1-dichloroalkyl ether, which decomposes to the acid chloride (equation 16). The reaction conditions are rather drastic. For instance -butyl benzoate has to be heated for 4 h at 180 °C in order to get a 90% yield of benzoyl chloride. The only stable and isolable 1,1-dichloro ether is a,a-dichloromethyl methyl ether, which, as described above, is used as a mild reagent for the conversion of carboxylic acids to their chlorides. Similarly severe conditions are required if the chlorine or bromine adduct of triphenylphosphine is selected. This reaction may be catalyzed by BF3. It has been applied successfully to unsaturated esters and to the cleavage of lactones. 

There are certain disadvantages to the carbonylation reaction, such as high temperature and pressure. An alternative preparation of trialkylmethanols is the use of the anion of dichloromethyl methyl ether. Addition of this anion to a trialkylborane is followed by three successive migrations to yield the trial-kylmethanol on oxidation. The reaction takes place at room temperature, and tertiary groups migrate without difficulty (Scheme 32). ... 

A 100-mL round-bottom flask containing a magnetic stirrer is capped with a rubber septum and charged with 15 mmol of borinate. 15 mL of diethyl ether arc added and the reaction is cooled to 0°C. 2.04 mL (22.5 mmol) of dichloromethyl methyl ether are added followed by 16.2 mL (30 mmol) of lithium lert-bu-toxide. The ice bath is removed and the mixture stirred at r.t. for 1 h. A slightly exothermic reaction develops and a white precipitate forms. The reaction mixture is cooled to 03C and 18 mL (45 mmol) of pH 8 phosphate buffer arc added, followed by 5.1 mL (45 mmol) of 30% hydrogen peroxide. The ice bath is removed and the mixture stirred for 12 h. The phases are separated, the aqueous phase extracted with two 15-mL portions of diethyl ether, the combined extracts washed with two 15-mL portions of water, then aq NaCl, dried over MgS04 and filtered. The volatiles are removed under reduced pressure and the residual oil is purified by bulb-to-bulb distillation. The chemical purity of the ketones is determined by GC using a 5% SP 2100 on Chromosorb W column and is usually >95%. The chiral ketones are further purified by preparative GC. For further examples, see Table 2. 

Dichloromethyl methyl ether, CH30CHC12, which can be regarded as the ester dichloride of orthoformic acid, does not give homogeneous products from alcohols and is thus, in general, unsuitable for preparation of alkyl chlorides.927... 

A very reactive agent for the preparation of acid chlorides is provided by (dichloromethyl)dimethylamine, (CHC12)N(CH3)2, which, analogously to dichloromethyl methyl ether, is to be regarded as the dichloride dimethylamide of orthoformic acid and is formulated as a salt (A).1104... 

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