A-chloroethyl

Deall lation. Chloroformates such as vinyl chloroformates (40) are used to dealkylate tertiary amines. Chloroformates are superior to the typical Von Braun reagent, cyanogen bromide, because of increased selectivity producing cleaner products. Other chloroformates such as aHyl, methyl, phenyl, and trichloroethyl have also been used in dealkylation reactions. Although the dealkylation reaction using chloroformates is mostiy carried out on tertiary amines, dealkylation of oxygen or sulfur centers, ie, ethers or thioethers, can also be achieved. a-Chloroethyl chloroformate [50893-53-3] (ACE-Cl) (41,42) is superior to all previously used chloroformates for the dealkylation reaction. ACE-Cl has the advantage that the conditions requked for ACE... 

A. ot-Chloroelhyl ethyl ether. A mixture of 200 g. (201 ml.) of redistilled paraldehyde, b.p. 121-122.5° (equivalent to 4.54 moles of acetaldehyde), and 200 g. (254 ml., 4.34 moles) of absolute ethanol is placed in a 1-1. three-necked flask fitted with a mechanical stirrer and a gas inlet tube reaching to the bottom of the flask. The mixture is cooled to —5° in a mixture of Dry Ice and acetone, and dry hydrogen chloride (Note 1) is passed into the stirred reaction mixture maintained at about —5° until 200 g. (5.48 moles) has been absorbed. During this operation, which requires about 2 hours, the reaction mixture separates into two layers. The upper layer of crude a-chloroethyl ethyl ether is re-... 

Benzoquinone a-Chloropropionic [Propanoic acid, 2-chloro ] 2-(a-Chloroethyl) [2,5-Cyclohexadiene-1,4-dione, 2-( 1 -chloroethyl) -] 45" 2... 

Tertiary aliphatic amines are also cleaved by HI, but useful products are seldom obtained. Tertiary amines can be cleaved by reaction with phenyl chloroformate R3N -h ClCOOPh —> RCl 4- R2NCOOPh. a-Chloroethyl chloroformate behaves similarly.Alkyl halides may be formed when quaternary ammonium salts are heated R4N+X" R3N -)- RX. ... 

Reaction of 256 with phosphorous oxychloride and DMF involves first formylation at the 6-position opening of the ketal to the enol ether by the HC1 produced in the Vilsmeier reaction would afford a hydroxyethyl side chain at C-3. This is no doubt converted to a chloroethyl group by excess oxychloride. There is thus obtained the antiinflammatory agent formocortal (257). 77... 

A new and interesting chioroformate reagent, a-chloroethyl chioroformate, was recently introduced for selective N-dealkylation of tertiary amines (106). When it was applied to the demethylation of 3a-acetoxytropane (2), the corresponding nor salt (198) was obtained in 97% yield (Scheme 20). 

Chloroethyl benzoate, 30,11 a-Chloroethyl ethyl ether, 36, 60 Chlorohydroquinone, 35, 27 -Chloromandelic acid, 35,14 Chloromethylation, 30, 68 2-Chloro-2-methylcyclohexanone, 37, 8... 

The reaction of nitrones of the 3-imidazoline series (295) with bromine and amyl nitrite, in the presence of base, gives a-tribromomethyl-(296) and a-hydroxyaminomethyl derivatives (297) (538). Bromination of nitrones (295) with N -bromosuccinimide (NBS) in CCI4 or bromine in methanol leads to the formation of a-bromoalkyl (298 a,b, Hal = Br) and a-dibromomethyl (299) nitrones (539-541). The reaction with iodine in methanol gives the mono iodo derivative (300) (541). The reaction with A-chlorosuccinimide (NCS) in CCI4 leads to a-chloroethyl nitrones (298b, Hal = Cl) and a,a-dichloromethyl nitrones (301) (Scheme 2.118) (225). 

There are cases where racemisation takes place under the influence of heat. Under such conditions there is homolytic fission of the bond between the asymmetric carbon atom and one of the substituents. The radical formed may assume either of the two enantiomeric configurations with equal possibility of recombination, giving a racemate. For example a chloroethyl benzene during distillation undergoes thermal racemisation, but in presence of lewis acids it undergoes racemisation with the intermediate formation of a carbocation. 

Ion-Formation from a-Chloroethyl Ethyl Ether and Antimony Pentachloride, P.H. Plesch and V.T. Stannett, Journal of Macromolecular Science Chemistry, 1982, A18, 425-430. 

Hex- and hept-2-en-4-yn-l-ol gave hexa-3,4-dienol and hepta-3,4-dienol, respectively. The absolute configuration of ( + )-hexa-3,4-dienol was determined to be S by thermal conversion of (- )-(S)-a-chloroethyl l-methylprop-2-ynyl ether (18) to an allenic aldehyde 19, which was reduced with LAH to (+ )-hexa-3,4-dienol (17, R = Me). (See Scheme 2.)... 

Chemical/Physical. Chlorination of 2-chloroethyl vinyl ether to a-chloroethyl ethyl ether or P-chloroethyl ethyl ether may occur in water treatment facilities. The alpha compound is very unstable in water and decomposes almost as fast as it is formed (Summers, 1955). Although stable in NaOH solutions, in dilute acid solutions hydrolysis yields acetaldehyde and chlorohydrin (Windholz et al., 1983). At pH 7 and 25 °C, the hydrolysis half-life is 175 d (Jones and Wood, 1964). 

A,r-Benzyl groups can be removed by reaction of amines with chloroformates. This can be a useful method for protecting-group manipulation if the resulting carbamate is also easily cleaved. A particularly effective reagent is a-chloroethyl chloroformate, which can be removed by subsequent solvolysis.78... 

Similarly, methyl a-chloroethyl ketone, a, -dichloroacetone and a,a,/3-trichlorobutyraldehyde have been converted phytochemically and in good yield to the corresponding primary or secondary halogenated alcohols. Since all these alcohols show optical rotation, it seems established that the phytochemical reduction generally takes an asymmetric course. (See pp. 80, 81, 88 and 92.)... 

The above mentioned reactions are widely used in alkaloid modification. A good example of alkaloid modifications for clinical curation purposes are opioides. Morphine and codeine are natural products of Papaver somniferum. However, the codeine is naturally produced in small amounts. This is one reason why it is produced synthetically from morphine by modification. As codeine is the 3-0-methyl ether of morphine, the mono-O-methylation occurs in the acidic phenolic hydroxyl. Pholcodine is obtained by modification of morphine through alkylation with A-(chloroethyl)morpholine. Moreover, dihydrocodeine, hydro-morphone and heroine are also obtained from morphine through modifications. 

By treating dyes that contain a chloroethyl group with thiourea, the cationic charge may be introduced in the form of an isothiouronium residue (e.g., 55) [150],... 

Ketone, methyl a-chloroethyl, phytochemical reduction of, IV, 81 —, methyl ethyl, phytoohemical reduction of, IV, 83... 

The synthesis of a number of radiolabelled apomorphine derivatives has been described.59-62 A full paper has appeared on the preparation of (—)-2,10,11-trihydroxy-/V-(n-propyl)noraporphine, a dopaminergic compound with anticonvulsant activity.63 The potential dopamine-inhibiting properties of (—)-N-(2-chloroethyl)norapomorphine and related compounds have been assessed. A-Chloroethylation in the aporphine series can abolish dopamine agonist action, and can confer a long-lasting dopamine antagonist potential.64... 

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