Methoxymethyl bromide

Bromomethyl methyl ether (Methoxymethyl bromide), BrCH2OCH3. Mol. wt. 124.97, b.p. 87°. Supplier Aldrich. 

The synthesis of the naphthoquinone 116 is shown in Scheme 3.24. Bromination of juglone (118) afforded the dibromojuglone derivative 134. Protection of the phenol group as its methoxymethyl ether formed the product 135 (50 % yield over two steps). Finally, the C-3 bromide substituent was regioselectively substituted with methoxide by heating 135 in methanol in the presence of sodium carbonate (96 %). The methoxy group was installed to impart electronic bias to the naphthoquinone in the TASF(Et) coupling (vide infra). 

Preparation of tetra(p-methoxymethyl) phenylphosphonium bromide — Preparation of a tetraarylphosphonium salt precursor to a pentaarylphosphorane... 

A solution of tri(p-methoxymethyl)phenylphosphine (0.500 g, 1.26 mmol) in dry methanol (5 ml) was placed in a pressure tube with a Teflon needle valve along with p-(methoxymethyl)bromoben-zene (0.255 g, 1.26 mmol) and anhydrous nickel(II) bromide (0.007 g, 0.032 mmol). The tube was flushed with dry nitrogen and closed. The tube was maintained in an oil bath heated at 180°C for 48 h. After cooling to room temperature, the solvent was evaporated under reduced pressure to give the crude product, which was purified by flash chromatography on silica gel (50 g) using 1 1 acetonitrile ethanol as eluent. In this manner was isolated pure tetra(p-methoxymethyl)phenylphosphonium bromide (0.050 g, 7%), which exhibited spectra and analyses in accord with the proposed structure. 

Analog laBt sich beispielsweise durch Kondensation von Benzaldehyd mit (5)-2-Amino-l-hydroxy-3-methyl-butan und Reaktion des so erhaltenen Imins mit Ethyl-magnesium-bromid ein Gemisch von zwei diastereoisomeren l-( l-Methoxymethyl-2-methyl-propyl-amino)-l-phenyl-propanen in 81 %iger Ausbeute erhalten3. 

Benzyl bromide can be converted into ethylbenzene (731) by the reaction of Me4Sn. The use of HMPA as a solvent is important. Overall inversion of configuration takes place at the chiral center of deuterated benzyl bro-mide[598]. The cyanomethylation[599] and methoxymethylation[600] of aromatic rings are carried out by the reaction of cyanomethyltributyltin (732) and methoxymethyltributyltin. 

Fig. 13 6-Methyl-2-[( )-(oxo-2-phenyl-l,3-oxazol-5(47/-ylidene)methyl]furo[2,3-fc] pyrrole-5-carboxylate 233b, 6-methoxymethyl-2-[( )-(oxo-2-phenyl-l,3-oxazol-5(4//-ylidene) methyl] furo[2,3-fc]pyrrole-5-carboxylate 233d [22] 3-benzyl-2-[( )-2-[5-(methoxycarbonyl)-6-methoxymethylfuro[2,3-fe]pyrrol-2-yl]vinyl -l,3-benzotiazolium bromide 234 [23]...

Starting from optically resolved carboxylic acid 215, the synthesis of bromide 218 encompassed three steps including performic acid treatment to 216, reductive fission of the lactone moiety to obtain 217, and double bromination. A three-step sequence involving mono-debromination, deacetylation and selective 2,3-O-isopropylidene protection converted 218 into exo-methylene precursor 219, on which C4 inversion to 220 was performed via mesylate. Changing the acetyl groups for methoxymethyl... 

The benzyl ether is prepared in a similar manner to the methoxymethyl ether, that is, by reaction of the conjugate base of the alcohol with benzyl bromide in an SN2 reaction. An example of a sequence that employs a benzyl ether protecting group is illustrated in the following sequence ... 

The next step was the introduction of the methylene acetal residue in 6 and 7 (Scheme 5). The initial plan was to effect this transformation in a single step, by exposure of the methoxymethyl derivatives 6 and 7 to dimethylboron bromide, following the conditions developed by Roush and co-workers (38). However, this reaction was not successful for either substrate, presumably due to competing cleavage of the acetonide residue. More promising results were obtained with triol 29 (obtainable from controlled hydrolysis of 7). Thus,... 

One of the mildest methods for preparing methylene acetals involves reaction of a diol with dimethoxymethane in the presence of a suitable activating agent such as phosphorus pentoxide,176 trimethylsilyl Inflate.177 or lithium bromide and p-toluenesulfonic acid.178 The reaction is also used to make methoxymethyl ethers (see section 4.4,1) from alcohols. Scheme 3,95 illustrates the simultaneous formation of a methoxymethyl ether and a methylene acetal from Shikimic Acid.169 The reaction was adapted to the synthesis of the methylene acetal moiety of the marine antitumour agent Mycalamide B [Scheme 3.96],179... 

ALDOL CONDENSATION (+)-(R)-l-Amino-2- methoxymethyl)pyrrolidine. Boron trichloride. Dialkylboron tri-fluoromethanesulfonates. Dibenzyl-ammonium trifluoroacetate. Di- -butylboryl trifluoromethanesulfonate. Dichlorodiethylaminoborane. Diiso-propylaluminum phenoxide. Diisopropyl-aminomagnesium bromide. Lithium diisopropylamide. Morpholine-Camphoric acid. Proline. 

Acetal esters such as methoxymethyl (Mom),P9 (2-methoxyethoxy)methyl (Mem),t l benzyloxymethyl (Bom),P l tetrahydropyranyl,P l 2-(trimethylsilyl)ethoxymethyl (SEM)t l and (methylsulfanyl)methyl (hltm) are sensitive to noild aqueous acids in THE as well as to mild Lewis acids such as magnesium bromide in diethyl ether (2 equiv, rt, l-24h).t l In addition. Bom esters may be cleaved by catalytic hydrogenation.P l In the absence of acid, acetal esters display reactivities typical for unhindered alkyl esters. Surprisingly, these esters... 

The reaction with halides such as methyl iodide, allyl bromide, benzyl bromide, bromomethyl acetate, or methoxymethyl chloride, to give the C-alkylated product, can be carried out in HMPT or without solvent.114... 

A similar well-defined graft copolymer consisting of polystyrene main chain and branches (G-7) can be prepared simply via repetition of copper-catalyzed living radical polymerizations.209 Thus, the synthesis starts with the copolymerization of styrene and />(acetoxymethy 1)styrene or />(methoxymethyl)sty-rene, followed by bromination of the substituent into the benzyl bromide moiety, which then initiates the copper-catalyzed radical polymerization of styrene to give graft polymers with 8—14 branches. 

Several extensions of this approach have been attempted, but none was successful. Only a faint odor results from the attempted synthesis of cyclopropa[Z)]naphthalene and none of the expected cyclopropa[a]naphthalene or cyclopropa[/]phenanthrene were generated in the corresponding reactions.- The same difficulties have been experienced with other benzyl derivatives. The reaction of 2-bromobenzyl bromide, 2-bromobenzyl chloride and 2-iodobenzyl bromide with butyllithium gave (partially) reduced bibenzyls or 9,10-dihydroanthracene, but no benzocyclopropene. Similarly, lithiation of 2-bromobcnzylsulfonates afforded only trace amounts (< 5%) of bcnzocyclopropene, while only methoxymethylbenzene was isolated on treatment of l-methoxymethyl-2-trimethylsiIylbenzene with fluoride ions. ... 

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