Dichloromethyl methyl ether reaction

Tertiary alkyl groups cannot be transferred readily in the carbonylation reaction or the cyanoborate process. In contrast, transfer of tertiary alkyl groups occurs smoothly in the dichloromethyl methyl ether reaction (Equation B3.16). 

Migration of tertiary alkyl groups in the dichloromethyl methyl ether reaction does however mean that ketones cannot be synthesized using thexylborane and the approach adopted in the carbonylation and cyanidation processes. In order to obtain ketones by this route, boranes bearing chloro or alkoxy groups, i.e. groups of very low migratory aptitude, have to be used as substrates (Equation B3.17). 

Frontier orbital theory predicts that electrophilic substitution of pyrroles with soft electrophiles will be frontier controlled and occur at the 2-position, whereas electrophilic substitution with hard electrophiles will be charge controlled and occur at the 3-position. These predictions may be illustrated by the substitution behaviour of 1-benzenesulfonylpyr-role. Nitration and Friedel-Crafts acylation of this substrate occurs at the 3-position, whereas the softer electrophiles generated in the Mannich reaction (R2N=CH2), in formylation under Vilsmeier conditions (R2N=CHC1) or in formylation with dichloromethyl methyl ether and aluminum chloride (MeO=CHCl) effect substitution mainly in the 2-position (81TL4899, 81TL4901). Formylation of 2-methoxycarbonyl-l-methylpyrrole with... 

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... 

Phosphorus pentachlonde, for conver sion of d l 10 camphorsulfomc acid to acid chloride, 46,14 reaction with methyl formate to yield dichloromethyl methyl ether, 47, 47... 

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. 

Titanium tetrachloride induces reaction with dichloromethyl methyl ether to give a, (3-unsaturated aldehydes.127... 

Scheme 9.1 describes reactions with several lithiated compounds, including dichloromethane, dichloromethyl methyl ether, phenylthiomethyl methyl ether, and phenylthioacetals. Compare the structure of these reagents and the final products for these reactions. Develop a mechanistic outline that encompasses these reactions. Discuss the features that these reagents have in common with one another and with carbon monoxide. 

This reactivity enables t/tro-substitution to be carried out at a specific position in the ring, irrespective of the presence of other contra-directing groups, and it allows the reaction to be carried out under mild conditions, or with weak electrophiles such as diazonium ions.2 Recent additions to the extensive list of electrophiles that have been used are toluene />-sulfonylisocyanate and ethoxycarbonyl isocyanate (Equation (53)),176 sulfonyl chloride,177 arene178 and silane sulfonyl chlorides,179 and dichloromethyl methyl ether (Equation (54)).1... 

Few data are available on the electrophilic substitution of dibenzofurans containing more than one substituent. 1,4-Dimethyldibenzofuran affords, as expected, the 2-aldehyde on reaction with dichloromethyl methyl ether and tin(IV) chloride. " The nitration of 2,4-dimethyldibenzofuran has also been studied. Acetylation of 4-methoxy-7-nitro- and 8-nitrodibenzofuran occurs exclusively at the 1-position. Similarly, both 4,6- and 3,4-dimethoxydi-benzofuran undergo bromination and acetylation at the 1-position. The acetylation of 1,3-dimethyl-, 1,4-dimethyl-, and 2,4-dimethyl-7-methoxydibenzofuran have been studied the acetyl group enters the 8-position. The chlorination of 3,7-dichlorodibenzofuran has also been studied. ... 

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 ... 

Besides 1-15 to 1-17, several other formylation methods are known.302 In one of these, dichloromethyl methyl ether formylates aromatic rings with Friedel-Crafts catalysts.303 ArCHClOMe is probably an intermediate. Orthoformates have also been used.304 In another method, aromatic rings are formylated with formyl fluoride HCOF and BF3.305 Unlike formyl chloride, formyl fluoride is stable enough for this purpose. This reaction was successful for benzene, alkylbenzenes, PhCl, PhBr, and naphthalene. Phenols can be regioselectively formylated in the ortho position in high yields by treatment with two equivalents of paraformaldehyde in aprotic solvents in the presence of SnCL and a tertiary amine.306 Phenols... 

To a solution of 2-(trimethylsilyl)ethyl (methyl 5-acetamido-4,7,8,9-tetra-0-acetyl-3,4-di-deoxy-D-gfycero-a-D-gafacto-2-nonulopyranosylonate)-(2— 3)-2,4,6-tri-0-benzoyl-p-D-galactopyranoside 30 (210 mg, 0.18 mmol) and zinc chloride (30 mg, 0.220 mmol) in dichloromethane (2 mL) was added a,a-dichloromethyl methyl ether (40 jj,L, 0.434 mmol) at 0°C. The reaction mixture was stirred at room temperature for 4 h, then diluted with dichloromethane, and washed successively with cold dilute aqueous sodium carbonate solution and water, dried over NajSOj, and concentrated to give the title product (187 mg, 96%) mp 75°C, [a]D +42.36° (c 1.015, CHC13). 

Acetylation and formylation are classical reactions in porphyrin chemistry. H. Fischer s synthesis of hemin, for which he was awarded the 1930 Nobel prize, required treatment of deuterohemin (49) with acetic anhydride (or acetyl chloride) in the presence of tin(IV) chloride as a Friedel-Crafts catalyst the product, 3,8-diacetyldeuterohemin-IX (50), was obtained in high yield. Fischer also accomplished formylation of iron porphyrins using dichloromethyl methyl ether and a Friedel-Crafts catalyst (B-37MI30700). Both of Fischer s examples resulted in peripheral substitution of unsubstituted iron porphyrins. However,... 

Allyl- and benzyl-thiophenes may be cyclized by a direct Bradsher reaction, using dichloromethyl methyl ether or related dichloroalkyl methyl ethers and tin(IV) chloride catalysis to give the corresponding benzo- or dibenzo-thiophenes in 55-60% yield (73JCS(P1)1099). Thus substituted thiophenes having a benzyl group at either the 2- or 3-position, e.g. (349), when treated with a 1,1-dichloroalkyl methyl ether and tin(IV)... 

To 40 mL dry CHjCL, there was added 6.07 g 2,5-dimethoxythioanisole, and this was cooled to 0 °C under N2. To this well stirred solution there was added 13.02 g stannic chloride over the course of 2 min. This was followed by the drop-wise addition of dichloromethyl methyl ether over 5 min, and the reaction mixture... 

To a vigorously stirred solution of 40.7 g 2,5-dimethoxyfluorobenzene in 215 mL CH,C12 cooled with an external ice bath, there was added 135 g of anhydrous stannic chloride. There was then added, dropwise, 26 g of dichloromethyl methyl ether at a rate that precluded excessive heating. The reaction mixture was allowed to come to room temperature over the course of 0.5 h, and then quenched by... 

Nakajima has shown that a-cyclopropyl acyl silane (23) results from reaction of 1-trimethylsilyl cyclopropyl lithium with dichloromethyl methyl ether at low temperature in THF solution, in a reaction said to involve a carbene intermediate and a 1,2-silicon shift (Scheme 56)147. 

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). 

Vilsmeier reaction), CICHOMe (from dichloromethyl methyl ether/titanium(iv) chloride), CC12 (from chloroform/sodium hydroxide, Reimer-Tiemann reaction), and 1,3-dithiane. 

A generally applicable method of formylation involves the reaction of an aromatic hydrocarbon and dichloromethyl methyl ether under Friedel-Crafts conditions (cf. Section 6.11.1, p. 1006). The intermediate chloroacetal (1) thus formed is readily hydrolysed to the corresponding aldehyde (e.g. p-t-butylbenzaldehyde, Expt 6.115). 

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