Chloro methylation

The formaldehyde may be replaced by methylal CHjlOCH,), or by chloro-methyl ether CHjOCHjCl, produced from paraformaldehyde, hydrogen chloride and methyl alcohol ... 

Oxidative cleavage of the complex 549 with CuCri affords 2,3-bis(chloro-methyl)-1,3-butadiene (550) and regenerates PdCri. Thus the preparation of this interesting dimerization product 550 can be carried out with a catalytic amount of PdCl2 and two equivalents of CuCb in MeCN[495], Similarly, treatment of allene with PdBr2 affords the dimeric complex 551. Treatment of this complex with 2 equiv, of bromine yields the dibromide 552. The tetra-bromide 553 is obtained by the reaction of an excess of bromine[496]. Similarly,... 

Researchers at Du Pont used hydroquinone asymmetrically substituted with chloro, methyl, or phenyl substituents and swivel or nonlinear bent substituted phenyl molecules such as 3,4- or 4,4 -disubstituted diphenyl ether, sulfide, or ketone monomers. Eor example,... 

A simple fragmentation pattern is also characteristic for chloro-, methyl- and amino-pyridazines. Pyridazinone fragments by loss of carbon monoxide followed by loss of N2 (Scheme 2). 

Imidazo[4,5-c]pyridine, 2-(2-aminophenyl)-diazotization, 5, 620 Imidazo[4,5-c]pyridine, 6-chloro-methylation, 5, 620... 

Dichlorothiophene can also be used for the synthesis of 3-substituted thiophenes, since it can be smoothly acylated and chloro-methylated in the 3-position, and the halogens can then be readily removed at the appropriate stage. 3-Thenylsuccinic acid (28) has thus been obtained by treating 2,6-dichloro-3-thenylsuccinic acid with sodium amalgam. 2-Bromo-3-thenylbromide can be utilized in a similar way. ... 

Nafimidone (93), an anticonvulsant compound, also contains an imidazole moiety It seems to have been discovered by accident during a search for antifungal agents Its synthesis is straightforward involving displacement with imidazole of the activated chlorine atom of chloro-methyl-p-naphthylketone (92) [32]... 

The acetic acid mother liquor, containing the rest of the reaction product, was concentrated in vacuo. The residue was dissolved in methylene chloride and washed with ice cold sodium carbonate solution. The organic solution was dried, concentrated in vacuo to a small volume and diluted with ether and petroleum ether. Fine yellow needles of 2-chloro-methyl-4-phenyl-6-chloroquinazoline 3-oxide precipitated. The pure base was recrystallized from a mixture of methylene chloride, ether and petroleum ether, MP 133° to 134°C. 

B) The preparation of (cis-1,2-epoxypropyi)phosphonic acid [ (1 -chloroethoxy )chloro-methyl] phosphonic acid (1.0 g) is added with stirring to tetrahydrofuran (50 ml) to which has been added a crystal of iodine and a zinc-copper couple (15.0 g). The mixture is then heated under reflux for 24 hr and the resulting solution filtered to yield (cis-1,2-epoxy propyl )-phosphonic acid. 

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 synthesis of vinylaziridines through reactions between allylic carbenoid reagents and imines (i.e., Darzen-type reactions) was first reported by Mauze in 1980 [13]. Treatment of aldimines or ketimines 16 with gem-chloro(methyl)allyllithium (17) afforded N-substituted vinylaziridines 18 (Scheme 2.6). Similarly, 2,3-trans-N-diphenylphosphinyl-2-vinylaziridines 21 were prepared with good stereoselectivities (trans cis= 10 1 Scheme 2.7) by treatment of a-bromoallyllithium (20) with N-diphenylphosphinyl aldimines 19 in the presence of zinc chloride [14]. 

Scheme 2.6 Aza-Darzen-type reaction with chloro(methyl) allyllithium (17).

HHTs derived from AMPA diethyl ester 56 also reacted with acetyl chloride to generate glyphosate nitriles 58 following cyanide displacement with the resulting iV-acetyl-Af-chloro-methyl-AMPA diethyl ester 57. Subsequent acidic hydrolysis of 58 gave GLYH3 (58). 

Methyl chloroformate Formic acid, chloro-, methyl ester (8) Carbonochloridic acid, methyl ester (9) (79-22-1)... 

Bromomethyl-3,4-dibromo-3,4-dihydrocoumarin 1 (Fig. 11.4) and its chloro-methylated analogue 2b rapidly and progressively inactivate a-chymotrypsin and also the activities of a series of trypsin-like proteases. A benzyl substituent characteristic of good substrates of a-chymotrypsin was introduced at the 3-position to make inhibition more selective. This substituted dihydrocoumarin 3 irreversibly inhibited a-chymotrypsin and other proteases. These functionalized six-membered aromatic lactones, and their five- and seven-membered counterparts, 3//-benzofuran-2-ones 2a26 and 4,5-dihydro-3//-benzo[b]oxepin-2-ones 2c,27 were the first efficient suicide inhibitors of serine proteases. Their postulated mechanism of action is shown in Scheme 11.2. 

Selection of appropriate conditions to modify polymers is facilitated by preliminary studies with well designed model compounds. The work with model systems is critical when studying condensation polymers because the main chain linkages have proved to be remarkably labile under certain conditions. Condensation of 4-chlorophenyl phenyl sulfone with the disodium salt of blsphenol-A yields 2,2-bis[4 -(4"-phenylsulfonylphenoxyl)phenyl] propane, T, an excellent model for the poly(arylene ether sulfone) substrate. Conditions for quantitative bromination, nitration, chloro-methylation, and aminomethylation of the model compound were established. Comparable conditions were employed to modify the corresponding polymers. 

The title compound and its 4.4 -chloro-. methyl- and methoxy-derivatives all... 

Halogenalkyl-substituted furazanes were also used for functionalization of the compounds. Thus, 3,4-bis(chloro-methyl)-l,2,5-oxadiazole 92 and 2(R)- fS>[ 3,5-bis(trifluoromethyl)pheny I ethoxy -3f.V,)-pheny I morpholine 93 gave 2W-[lW-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-4-(4-dimethylaminomethyl-l,2,5-oxadiazol-3-yl)methyl-3( 3 Tphenyl-morpholine 94 (Equation 21) <1996W09629328>. 

O-Alkylation of 4-hydroxy-3-morpholino-l,2,5-thiadiazole 132 has been achieved with the chiral cyclic chloro-methyl sulfite 133 which subsequently suffers ring opening on treatment with simple alcohols <2001RCB436> or alkylamines <2002RJ0213> to afford the timolol analogues 134 with very little racemization (Scheme 20). This indicated an almost exclusive attack of the oxy anion on the exocyclic carbon atom and is a significant improvement on the previous oxirane method, which suffers from racemization. An alternative biocatalytic asymmetric synthesis of (A)- and (R)-timolol has also appeared <2004S1625>. 

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