Halomethyl ethers

WO07895, 20010L1689>. Adenine-fused oxadiazepinium salts were prepared similarly from adenine and bis(halomethyl) ethers <1989HCA1495>. 

G. R. Ames, H. M. Blackmore, and T. A. King., Reaction of sugars with halomethyl ethers,... 

The most frequentiy used halo alkylating agents are aldehydes and hydrogen haUdes, haloalkyl ethers, haloalkyl sulfides, acetals and hydrogen haUdes, di- and polyhaloalkanes, haloalkenes, haloalcohols, haloalkyl sulfates, haloalkyl -tosylates, and miscellaneous further haloalkyl esters. Haloalkylations include halomethylation, haloethylation, and miscellaneous higher haloalkylations. Under specific conditions, bis- and polyhaloalkylation can also be achieved. 

Heating 6-bromo- and 6-chloro-2-halomethyl- (99JHC1065) and 6-bromo-, 6-chloro- and 6-fluoro-2-phenyl-4/f-pyrido[l, 2-u]pyrimidin-4-ones (00JMC2814) in phenyl ether at 220 °C for 10 min yielded the appropriate 7-halo-1,8-naphthyridin-4-ols. 6-Amino-2-trifluoromethyl-4//-pyrido[l, 2-a]-pyrimidin-4-one was transformed into 7-amino-2-trifluoromethyl-l,4-dihy-dro-l,8-naphthyridin-4-one in 90% yield (98EJM383). 

The chemical modification of poly(arylene ether sulfone)s has already been described in numerous papers. They relate to sulfonation, fluorination, and halomethylation. These derivatives are particularly suitable for the preparation of hydrolysis- and temperature-resistant separation membranes. They are used already for sea water desalination, and also for the separation of gas mixtures. 

Examples of the preparation of cyclopropanes by intramolecular nucleophilic substitution are illustrated in Scheme9.17. The first example is a synthesis of [l.l.ljpro-pellane, which yields the product in acceptable yields, despite the high strain and poor stability of this compound [66]. The second and third examples illustrate the remarkable ease with which 3-halopropyl ketones cyclize to yield cyclopropanes instead of cyclic, five-membered enol ethers or ketones. Similarly, carbamates of 2-haloethylglycine esters do not undergo intramolecular N- or O-alkylation on treatment with bases, but yield cyclopropanes instead [67, 68]. Some nucleophiles can undergo Michael addition to 3-halomethyl acrylates faster than direct Sn2 reaction, to yield cyclopropanes by cyclization of the intermediate enolates (fourth example, Scheme9.17) [69]. 

When a solution of tellurium dioxide in concentrated hydrochloric or hydrobromic acid was added to a solution of allyl cinnamate in diethyl ether cooled to — 30°, only the allyl-double bond reacted3. The allyl group rearranged during the addition of X3Te—X forming l-halomethyl-2-trihalotelluro-l-ethyl cinnamates. 

Denmark et al. studied the effect of zinc iodide on the catalytic, enantioselective cyclopropanation of allylic alcohols with bis(iodomethyl)-zinc as the reagent and a bismethanesulfonamide as the catalyst 17]. They found significant rate enhancement and an increased enantiomeric excess of the product cyclopropane upon addition of 1 equivalent zinc iodide. Their studies and spectroscopic investigations showed that the Schlenk equilibrium appears to lie far on the left (IZnCHjI). Charette et al. used low temperature - C-NMR spectroscopy to differentiate several zinc-carbenoid species [18]. They also found evidence that in the presence of zinc iodide, bis(iodomethyl)zinc is rapidly converted to (io-domethyOzinc iodide. Solid-state structures of (halomethyl)zinc species have been described by Denmark for a bis(iodomethyl)zinc ether complex (6a) [19] and Charette for an (iodo-methyl)zinc iodide as a complex with 18-crown-6 (6b) [20] (Fig. 2). 

The ether 153 was the result of attempts to convert 1-hydroxy-methylphenothiazine (152) into the corresponding halomethyl derivatives by means of halogen acids. ... 

Allowing hydrogen halides to react with aliphatic aldehydes under the above conditions but in absence of an alcohol leads to bis-(a-haloalkyl) ethers (c) for example, bis-(l-chloroethyl) ether1000,1001 and bis(halomethyl) ethers1002 are thus obtained. 

Nowadays, phase-transfer catalysis has proved to be particularly effective in the generation of carbenes by a-ehmination. The halomethyl anion is transported as an ion-pair with a tetraalkylammonium ion, or a crown ether-complexed alkah-metal ion, from a strongly basic aqueous solution into an organic phase, where ehmination takes place and the resulting carbene reacts with the substrate in organic phase to give halocyclopropanes (Scheme 5.11). 

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