ATROPALDEHYDE

I-Dichloro-2-phenylcyclopropane. In a 1-L, three-necked, round-bottomed Morton flask (Note I) equipped with a me- 

The temperature is allowed to rise to 40°C and then kept between 40°C and 45°C by cooling with water (Note 3). After about an hour evolution of heat subsides, and the dark reaction mixture is heated to 55-60°C for an additional hour. The products are transferred to a 1-L separatory funnel with 250 mL of water and shaken. The organic layer is separated and the aqueous phase extracted with 25 mL of petroleum ether (Note 4). The organic fractions are combined, dried over anhydrous magnesium sulfate powder, filtered, concentrated in vacuo, and distilled through a 20-cm Vigreux column. A forerun at about 50°C (16 mm) consists mainly of styrene. Distillation of the remainder affords 80-82 g (86-88%) of dichlo-rophenylcyclopropane, bp 118-120°C (16 mm) (Note 5). 

Atropaldehyde diethyl acetal. A mixture of 18.7 g (0.100 mol) of l,l-dichloro-2-phenylcyclopropane, 16 g (0.40 mol) of sodium hydroxide, and 160 mL of ethanol is placed in a 250-mL flask fitted with a reflux condenser. The mixture is heated under reflux for 24 hr. Some bumping may occur. Water (200 mL) is added, and the mixture is extracted with three 30-mL portions of petroleum ether. The extracts are combined, dried as above with magnesium sulfate, concentrated in vacuo, and distilled through a 20-cm Vigreux column. The acetal begins to distil at about 70°C (0.5 mm), and the product is collected until the temperature reaches about 100°C. The yield is 14-15 g (68-73%). Gas chromatographic analysis of the product shows it to be about 85% pure (Note 6). 

Atropaldehyde. The acetal (15 g), placed in a 100-mL flask fitted with a magnetic stirrer and a thermometer, is cooled to about 4°C in an ice bath. A mixture of 15 mL of formic acid and 4 mL of water is similarly cooled and added in one lot with stirring to the acetal. The temperature drops to about -4°C. The homogenous mixture is stirred for 60 sec and then quenched by adding 15 mL of petroleum ether and 25 mL of water. The mixture is transferred to a separatory funnel and thoroughly shaken. The aqueous phase is extracted with two additional 15-mL portions of petroleum ether, and the combined extracts are dried as above with magnesium sulfate and concentrated in vacuo (Note 7). A mixture of 10 mL 

The submitters used Merck styrene 99%, stabilized with 4-te/7-butylpyrocatechol. Triethylbenzylammonium chloride was prepared by refluxing equimolar amounts of triethylamine and benzyl chloride in ethanol for 2 hr and removing the solvent in vacuo. The salt is commercially available. The other reagents were technical grade. 

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Bismuth molybdate catalysts can also cause other allylic oxidations such as the conversion of 2-methylpropene to methacrolein and a-methylstyrene to atropaldehyde, and ammoxidations such as the conversion of 2-methylpropene to methacrylonitrile and a-methylstyrene to atroponitrile.309... 

The present method is fast and affords labile aldehyde that is pure enough to allow crystallization. None of the conditions suggested by Gorgues for hydrolysis of acetals are satisfactory for the preparation of atropaldehyde.15143... 

Atropaldehyde diethyl acetal (8) 1-Propene, 3,3-diethoxy-2-phenyl-... 

The method presented here is a simple procedure for the preparation of pure atropaldehyde via its stable acetal, starting from inexpensive chemicals. 

Syntheses of acetals of atropaldehyde have been reported previously, but all required either multistep sequences or difficultly accessible starting materials.5,6 Thus the ethylene glycol acetal has been prepared from 2-phenylpropanal in a three-step procedure.5 Ring openings of dihalocyclopropanes to give acetals are well known.7-10 The reaction of l,l-dichloro-2-phenylcyclopropane with methanolic sodium methoxide has been shown to give 1-phenyl-2,2-dimethoxycyclopropane. u... 

The only described preparatively useful route to atropaldehyde is the hydrolysis of the ethylene glycol acetal mentioned above.5... 

ATROPALDEHYDE, 60, 6 Atropaldehyde diethyl acetal, 60, 7 13-Azabicyclo[7.3.1 ]tridecan-5-ol, stereoisomer [61714-12-3], 61, 103 2-Azido-2-phenyladamantane, 60, 104... 

Because felbamate-induced aplastic anemia might be linked to the formation of atropaldehyde, a urine screening test has been developed that indirectly assesses the formation of this toxic metabolite (8). The risk of serious toxicity may also be related to HLA status, and HLA typing is being performed in patients entered in the manufacturer s felbamate registry. The potential value of these tests in reducing the risk of toxicity remains to be established. 

Thompson CD, Gulden PH, Macdonald TL. Identification of modified atropaldehyde mercapturic acids in rat and human urine after felbamate administration. Chem Res Toxicol 1997 10 457-462. 

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