A-Chloro chloroformates

Phosgene, diphosgene, and triphosgene react readily with a variety of aldehyde substrates under mild conditions thereby affording the corresponding a-chloro chloroformates in good yields [48-51],... 

A method for the preparation of a-chloro chloroformates using triphosgene was developed by Coghlan (Table 4.4) [51],... 

Typical procedure. Cyclohexyl a-chloro chloroformate [51] To a mechanically stirred solution of cyclohexane carboxaldehyde (4.05 g, 36.1 mmol) and pyridine (300 mg, 3.79 mmol) in CCI4 (40 mL) under a nitrogen atmosphere at -20 °C, solid triphosgene (5.37 g, 18.1 mmol) was added at such a rate that the reaction temperature remained between —20 and —10 °C ( 5 min). The resulting viscous slurry was allowed to warm to room temperature over 90 min, and then heated to 40 °C for 1 h. The reaction mixture was allowed to cool and stirred overnight at room temperature. Filtration of the pyridinium salts followed by removal of the solvent in vacuo gave 8 g of crude product, which was purified by distillation (bp 90-91 °C at 10 Torr), thereby affording the desired cyclohexyl a-chloro chloroformate (6.80 g, 89%). 

In an attempt to effect a chloroformate-mediated dealkylation of aziridine lactone 119 (Scheme 3.41), Dodd and co-workers observed aziridine ring-opening, a-Chloro lactone 120 was obtained in 72% yield [32]. 

ChT.ORODTTSOPROPYLPHOSPHINE, 48, 47 a-Chloro ethers as intermediates in de-methylation of anisoles, 47, 24 Chloroform, condensation with benz-aldehyde, 48, 27... 

In order to construct the L-asparagine derivative of per-O-acetylated 0-(2-acetamido-2-deoxy-/ -D-glucopyranosyl( 1 — 4)-2-acetamido-2-deoxy-D-glucose (7), Spinola and Jeanloz (13) used (the sensitive) silver azide for conversion of the a-chloro anomer of the chitobiose derivative 8 into the / -azido derivative 9. Kunz and associates (14,15) have accomplished the conversion of the a-chloro anomer of 8 into 9 using sodium azide in the presence of tri-n-octyl-methylammonium chloride as a phase-transfer catalyst in chloroform water. 

B) Examination of the Solvents insoluble in Water. These may be carbon disulphide, chloroform, carbon tetrachloride, a chloro-derivative of ethane or ethylene, a chlorohydrin, amyl alcohol, amyl acetate, ether, benzene or a homologue, oil of turpentine, pinewood oil, light mineral oil, resin oil, tar oil, shale oil, or camphor oil. 

Nitrosation of 4-hydroxythiocouTnarin leads to the 3-oxiniino-4-keto derivative (45). Replacement of the 4-hydroxy group by a chloro (46), arylamino (47), or phenylhydrazino group (48) is readily accomplished by heating the compound with phosphorus pentachloride in chloroform, aniline, or phenylhydrazine, respectively. ... 

Even more surprising, we discovered that 2,2-dichlorovi-nyl chloroformate is isolated in 50% distilled yield when chloral is treated with phosgene and zinc dust in methyl acetate (Ref. 167). Efforts were made to generalize this process by extending the reaction to other a-chloro and a-bromo aldehydes and ketones as shown in table 3-18 (Ref. 167). 

B. Alkylation of (LIX) with halo carboxylic acids or esters (preferably chloroformic acid or a-chloro carboxylic acids) followed by treatment of the intermediate (LXVII) with alkali which causes a mercapto carboxylic acid to be split off. The 2-(hydroxyalkyl) isothiocyanate (LXVI) formed cyclizes into (LXI) 314, 328). 

A 1 4 mixture of methyl o-nitromandelate (116 R1 = OH, R2 = H) and thionyl chloride at room temperature yields not the expected a-chloro compound (116 R1 = Cl, R2 = H), but the 5-chloroanthranil-3-carboxylate (118 R = H).144 Reaction conditions are, however, critical for example, neat thionyl chloride at room temperature produces only the sulfite ester of 116, whereas in pyridine at — 80°C the a-chloro compound (116 R1 = Cl, R2 = H) is obtained. The chloromandelate (116 R1 = OH, R2 = Cl) is inert to boiling thionyl chloride, but on prolonged (12 h) treatment with thionyl chloride in chloroform it yields the dichloroanthranil 118 (R = Cl). A mechanistic rationale (Scheme 16) involving the sulfinyl chloride 117 is proposed. 

Nitrile oxides are conveniently generated in situ by dehydration of primary nitro compounds (with phenylisocyanate or ethyl chloroformate or di-tert-butyl dicarbonate) or from a-chloro-oximes (by treatment with a base). The nitrile oxide reacts with an alkene to form an isoxazoUne or with an alkyne to give a heteroaromatic isoxazole (3.131). Nitrile oxides are prone to undergo dimerization, although this can be minimized by maintaining alow concentration of the dipole in the presence of the dipolarophile. 

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