Dichloromethyl methyl ester

If the pKa of the corresponding acid R1 - H from the stabilized carbanion is smaller than 35, the migration of R1 fails in (dichloromethyl)borate complexes. Failure to convert pinanediol [(phenylthio)methyl]boronate to an a-chloro boronic ester has been reported15. Reaction of (dichloromethyl)lithium with an acetylenic boronic ester resulted in loss of the acetylenic group to form the (dichloromethyl)boronate, and various attempts to react (dichloromethyl)boronic esters with lithium enolates have failed17. Dissociation of the carbanion is suspected as the cause, but in most cases the products have not been rigorously identified. 

Treatment of the dichloromethyl derivative 472 with sodium cyanide gave290 an almost quantitative yield of the epimeric nitriles (480, 481). The mixture could not he separated by chromatographic methods, but differences in reactivity of the stereoisomers towards methanolic hydrogen chloride allowed isolation of only one ester, namely, 482 the trails cyanide underwent ready conversion into the methyl ester, whereas the cis compound gave a rather complicated mixture of products, with amide 483 being identified as the major component. Reduction of the ester group in 482, followed hydrolysis of the dichloromethyl group, afforded DL-t/ireo-DL- Y/o-octose, characterized as the heptaacetate, and identified as threo-ido-octito by comparison with an authentic sample. 

Chiral ketones.3 Asymmetric hydroboration of a prochiral alkene with monoisocampheylborane followed by a second hydroboration of a nonprochiral alkene provides a chiral mixed trialkylborane. This product reacts with acetaldehyde with elimination of a-pinene to give a chiral borinic acid ester in 73-100% ee. Treatment of this intermediate with a,a-dichloromethyl methyl ether (2,120 5, 200-203) and lithium triethylcarboxide followed by oxidation results in an optically active ketone in 60-90% ee. 

Asymmetric hydroboration 2171 of prochiral alkenes with monoisopinocampheyl-borane in the molar ratio of 1 1, followed by a second hydroboration of non-prochiral alkenes with the intermediate dialkylboranes, provides the chiral mixed trialkylbo-ranes. Treatment of these trialkylboranes with acetaldehyde results in the selective, facile elimination of the 3-pinanyl group, providing the corresponding chiral borinic acid esters with high enantiomeric purities. The reaction of these intermediates with base and dichloromethyl methyl ether provides the chiral ketones (Eq. 130)2l8>. A simple synthesis of secondary homoallylic alcohols with excellent enantiomeric purities via B-allyldiisopinocampheylborane has been also reported 219),... 

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. 

Chiral boronic esters react with organolithium reagents to form diorganylalkoxyboranes (borinic esters). Subsequent reaction with the anion of dichloromethyl methyl ether then yields chiral ketones by rearrangement of both of the groups on boron (Scheme 42). No racemization is observed in this sequence and alkyl-, aryl- or alkynyl-lithium reagents can be used. 

Alkylborinic esters, obtained from alkylboronic esters and an organometallic reagent, are converted into the corresponding ketones by the reaction with dichloromethyl methyl ether in the presence of a hindered base, followed by oxidation with hydrogen peroxide in pH 8 buffer or with anhydrous trimethylamine Ar-oxide18. 

The electrophilic substitution of indoxazene-3-acetic acid and its derivatives has been investigated extensively. Chlorination with chlorine in acetic acid or with a slight excess of N-chlorosuccinimide produces a mixture of the a-chloroacetic acid (30 R1 = Cl, R2 = H) (48.6%) and 3-(dichloromethyl)-indoxazene (5%), whereas with a large excess of N-chlorosuccinimide a mixture of 3-(dichloromethyl)- and 3-(trichloromethyl)indoxazene results 47 Iodination with iodine monochloride in acetic acid, or bromination with an equivalent of bromine in the same medium, yields only the monohalogeno acids (30 R2 = H, R1 = I and Br, respectively).47-49 With an excess of bromine, 3-(tribromomethyl)indoxazene is formed.48 49 Surprisingly, bromination of the methyl ester (30 R1 = H, R2 = Me), even with an excess of... 

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... 

Dihalo ethers also give orthocarboxylic esters readily, by reaction with alkali alkoxides 890 e.g., mixed esters of orthoformic acid are formed on treatment of dichloromethyl methyl ether with various alkoxides,891 and esters of orthooxalic acid are obtained by heating l,l,2,2-tetrachloro-l,2-diethoxyethanes with sodium alkoxides in an autoclave 892... 

Other reactions forming sulphonyl halides from sulphonic acid derivatives include sulphonyl chlorides from esters with PC13647, sulphonyl fluorides from anhydrides with fluoride salts627 and sulphonyl chlorides from trimethylsilyl derivatives of sulphonic acids by reaction with dichloromethyl methyl ether648. 

Disubstituted pyrroles lacking substituents at the 3- and S-positions are often required in porphyrin synthesis, and these can now be prepared from pyrrole itself. Thus, trichloroacetylation or trifluoroacetylation of pyrrole affords the 2-trihaloacetylpyrrole 8, which can be converted into the corresponding esters 9, carboxylic acids, or amides. The amides have been acetylated, or formylated, at the 4-position specifically, and the resulting acyl pyrroles (10) have been reduced to the alkyl pyrroles (11). This general procedure has now been improved by direct Friedel-Crafts formylation of the trichloroacetylpyrrole (8a) with dichloromethyl methyl ether (aluminium chloride) to the diacylpyrroles... 

To that end they converted dichloroacetonitrile to 2-(dichloromethyl)-4-oxazo-line carboxylic acid methyl ester 355 in 88% yield. Treatment of 355 with one equivalent of sodium methoxide produced 356 via an internal transfer of oxidation state through a molecular framework. The synthesis was completed by acid-catalyzed elimination of methanol to afford 357 in 48% overall yield from dichloroacetonitrile. 

Cl Hi6N2O3S2, Epidithiopiperazinedione antibiotic A26771A, 40B, 477 C14H20N2O2S, N-Acetylthienamycin methyl ester, 44B, 461 Cl4H2iBrCl2N206 2 H2O, 2-Amino-N-(3-dichloromethyl-3,4,4a,5,6,7-hexahydro-5,6,8-tr ihydroxy-3-methyl-1-0x0-1H-2-benzopyran-4-yl)pro-... 

Pyrrole-3,5-dicarboxylic acid, 2-dichloromethyl-4-methyl-diethyl ester... 

This topic has been reviewed [2, pp 94, 100-111, 130-134] All of the standard approaches to the synthesis of a compound like methyl 2-fluorostearate from methyl 2-bromostearate result mall yield of the 2-fluoro ester and the unsaturated esters. Although silver fluoride is not a new reagent, its use moist in wet acetonitrile to convert methyl 2-bromostearate to its fluoro ester is a departure from the traditional set of anhydrous conditions (Procedure 6, p 194) [71] In contrast, silver tetrafluoroborate converts a-chloroketones to their respective fluoroketones under anhydrous conditions. The displacement of less activated halogen groups by silver tetrafluoroborate to form their respective fluorides is novel Although silver tetrafluoroborate could not be used to convert an aliphatic terminal dichloromethyl or trichloromethyl group to its corresponding fluoro derivative, it is an effective fluorine source in other situations [72] (Table 8)... 

Precedents for these reactions include insertion of a CHC1 group from (dichloromethyl)-lithium into the triarylborane C - B bond6 7, the preparation and reactions of achiral (dichloro-methyl)boronic esterss, and reactions of achiral boronic esters with (dichloromethyl)lithium9,10. 

Reaction with carboxylic adds. A surprising finding is that phenyl(bromodichIoro-methyl)mercury reacts with carboxylic acids in benzene at 60-80° in about 45 min. to give dichloromethyl esters in high yield phenylmercuric bromide is produced in virtually quantitative yield ... 

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