B. Synthesis of other alpha-aryl ketonesExperimentalPreparation of other alpha-aryl ketones and N-(beta-aralkyl)-hydroxylamines. - By treating the corresponding nitroolefins with a 20% excess of the amount of LAH necessary for the reduction of the double bond via reverse addition at -40 to -50°C, followed by hydrolysis by means of the rapid introduction of 400 mL of 6 N HCl, and steam distillation of the aqueous phase, the ketones, listed in Table I
(cf original text), were prepared. The corresponding N-(beta-aralkyl)-hydroxylamines were isolated in low yields by making the aqueous acidic solution through which the steam had been passed, alkaline and extracting with ether.
1-o-Chlorophenyl-2-nitropropene-1. -
A. Modified Knoevenagel-Walter Synthesis. There were refluxed together for 8 hours, 28.1 g (0.2 mole) of o-chlorobenzaldehyde, 15.0 g (0.2 mole) of nitroethane, 1.74 g (0.02 mole) of n-amylamine and 30 mL of absolute alcohol. On cooling, the mixture was stored in the refrigerator until the precipitation was complete. The mixture was filtered and the precipitate washed with a few mL of absolute alcohol. There were thus obtained 20.0 g of 1-o-chlorophenyl-2-nitropropene-1. An additional amount of 2.0 g was obtained by concentration of the filtrate and washings, bringing the total yield to 56%.
B. Knoevenagel-Walter synthesis. 21 - When the same quantities of the above reagents were mixed and allowed to stand at room temperature for 2 weeks, and the product was isolated in the same manner, there was obtained a total yield of 24.1 g (61%) of 1-o-chlorophenyl-2-nitropropene-1. Recrystallization from absolute ethanol produced bright yellow crystals, mp 40°C. Anal.: Calcd for C9H8ClNO: C, 55.00; H, 4.08. Found: C, 54.98; H, 3.88.
2-Thienylacetoxime. - When 2-thienylacetone was treated in the usual manner
22 for the preparation of an oxime there was obtained, on recrystallization from petroleum ether (bp 60-75°C), a white crystalline product, mp 91-92°C, which was not depressed when mixed with a sample prepared according to the method of Bouveault and Wahl
2e by the action of aluminium amalgam on 1-(2-thienyl)-2-nitropropene-1.
DiscussionThe preparation of the ketones listed in Table I demonstrated the general applicability of this method of synthesizng carbonyl compounds from beta-arylnitroölefins. In general, the yields were good, the lowest (43%) being obtained from the relatively unstable 1-(2-thienyl)-2-nitropropene-1. The ketones are assumed to arise via the same mechanism as did phenylacetone in the previous experiment, i.e. by a modified Nef reaction after the selective reduction of the double bond of the nitroalkene.
The substituted hydroxylamines listed in Table I all readily reduced Tollens reagent at room temperature.
The experiments on the synthesis of the previously unreported 1-o-chlorophenyl-2-nitropropene-1 showed a slightly higher yield for the Knoevenagel-Walter synthesis (61% vs 56%) as compared to the much shorter reaction time of the modified Knoevenagel-Walter synthesis (8 hours vs 14 days).
The authenticity of the oxime prepared from 2-thienylacetone was proven by means of the mixed melting point determination with the sample obtained by the reduction of 1-(2-thienyl)-2-nitropropene-1 with aluminum amalgam.
C. Reduction of omega-nitrostyreneExperimentalReduction of omega-nitrostyrene to beta-phenylethylamine, N-(beta-phenylethyl)-hydroxylamine and phenylacetaldoxime. - When 2.13 g (0.056 mole, half the amount necessary for the reduction of the nitro group) of LAH dissolved in 100 mL of absolute ether, was added to 11.2 g (0.075 mole) of omega-nitrostyrene at -30 to -40°C as before and after hydrolysis with 20% aqueous sodium potassium tartrate, a mixture of products was obtained. Upon distillation, there was isolated 0.5 g (6%) of beta-phenylethylamine, bp 72-77°C (6.0 mm). The residue
11b in the distilling flask was dissolved in ether and extracted with an excess of 1 N HCl. After removal of the ether by distillation there was obtained 1.6 g (16%) of phenylacetaldoxime which melted at 97-98°C after recrystallization from petroleum ether (bp 60-75°C). The recorded
23 mp is 97-99°C. Anal.: Calcd for C8H9NO: C, 71.09; H, 6.71. Found: C, 71.03; H, 6.45. Neutralization of the acidic washings with dilute aqueous sodium carbonate afforded 3.4 g (33%) of N-(beta-phenylethyl)-hydroxylamine. After recrystallization from light petroleum ether, it melted at 83-84°C. Anal.: Calcd for C8H11NO: C, 70.04; H, 6.71. Found: C, 70.12; H, 7.93.
Phenylthioureide of beta-phenylethylamine. - This white crystalline substance was synthesized according to the previously utilized procedure
4. Its mp was 110-110.5°C. The mp was previously reported
24 as 111°C. Anal.: Calcd for C15H16N2S: C, 70.27; H, 6.29. Found: C, 70.38; H, 6.10.
beta-Phenylethylamine hydrochloride. - This compound was prepared by the previously described procedure. It was recrystallized from an absolute alcohol-ether combination. It mp was 215-217°C. Literature
25 records the mp as 217°C.
Action of 2,4-dinitrophenylhydrazine sulfate on phenylacetaldoxime. - When 0.5 g of phenylacetaldoxime was treated according to the prveiously utilized procedure for the preparation of a 2,4-dinitrophenylhydrazone, there was obtained an orange crystalline solid, mp 121-121.5°C, which did not depress the mp of an authentic sample of the 2,4-dinitrophenylhydrazone of phenylacetaldehyde.
N-(beta-phenylethyl)-p-nitrophenylnitrone. - When 2.7 g (0.02 mole) of N-(beta-phenylethyl)-hydroxylamine dissolved in 6 mL of absolute alcohol, and 0.3 g (0.02 mole) of p-nitrobenzaldehyde dissolved in 10 mL of absolute alcohol had been mixed together, the solution started to deposit yellow crystals after 2 hours standing at room temperature. After 24 hours the precipitate was filtered and recrystallized from absolute alcohol. In this way there was obtained a yellow crystalline solid, mp 157-158°C. Anal.: Calcd for C15H14N2O3: C, 66.65; H, 5.22. Found: C, 66.75; H, 5.29.
N-(beta-phenylethyl)-hydroxylamine oxalate. - The neutral oxalate was prepared as previously described and recrystallized from a methanol-ether combination. Its mp was 165.5-167°C with decomposition. Anal.: Calcd for C18H24N2O6: C, 59.30; H, 6.59. Found: C, 59.85; H, 6.49.
Phenylacetaldehyde. - When 0.855 g (0.0225 mole, a 20% excess for the reduction of the double bond) of LAH was treated with 11.2 g (0.075 mole) of omega-nitrostyrene via reverse addition at -40 to -50°C and hydrolysis was brought about by 400 mL of 6 N HCl introduced rapidly, there was obtained after steam distillation of the acidic hydrolytic mixture and rectification, 0 to 0.46 g (0-5%) of phenylacetaldehyde, bp 61-65°C (5.0 mm).
When hydrolysis of the intermediate organometallic complex was effected with the calculated amount of 1 N HCl, added slowly, the ether layer afforded a crude yellow oil which, when treated according to the nitrous acid test, gave an orange-red coloration comparable in shade and intensity to that given by 1-nitrobutane when similarly treated.
The crude oil was then triturated with a solution of 4.0 g of sodium hydroxide in 75 mL of water to yield a dispersion which, when added to an ice cold solution of 12.5 mL of sulfuric acid in 80 mL of water during rapid stirring (Nef reaction), allowed the separation of 0.92 g (10%) of phenylacetaldehyde, bp 63-64°C (5.0 mm).
The methone derivative of phenylacetaldehyde was prepared by the usual method.
26 Its mp was 164-165°C, the same as reported previously.
27The 2,4-dinitrophenylhydrazone of phenylacetaldehyde was prepared as before. Its mp was 121-121.5°C which was not depressed when mixed with an authentic sample.
DiscussionIn general, the experiments on the reduction of omega-nitrostyrene via the reverse addition of LAH indicated that it behaved similarly to 1-phenyl-2-nitropropene-1. In most cases, the same derivatives were prepared to characterize the various products.
However, a dissimilarity showed itself in the synthesis of the carbonyl derivative insofar as the yield of phenylacetaldehyde was very low. It is believed that here the mechanism of the reduction is still comparable while the ease of hydrolysis differs. The facts that a positive nitrous acid test was obtained for a primary nitro group and that the yield of phenylacetaldehyde marks the first reliable synthesis of the next higher homolog of benzaldehyde via omega-nitrostyrene, since the reported reduction of omega-nitrostyrene to the aldoxime followed by hydrolysis to the aldehyde,
28 has been described as being incapable of repetition.
29.
References1. condensed from a part of the dissertation submitted to the Graduate Faculty of Fordham University in partial fulfillment for the degree of Doctor of Philosophy.
2. (a) RF Nystrom e.a. JACS 69, 1197 (1947) (b) 69, 2548 (1947) (c) 70, 3738 (1948).
3. RT Gilsdorf e.a. JOC 15, 807 (1950).
4. FA Hochstein e.a. JACS 70, 3484 (1948).
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6. The reduction of omega-nitrostyrene to 2,3-diphenyl-1,4-dinitrobutane has been reported
5f.
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11. (a) This fraction was incorrectly described as benzyl methyl ketimine in our preliminary communication, JACS 72, 4327 (1950). The hydrated trimer of the imine mentioned, actually was the hydroxylamine derivative; (b) similarly, a mixture of phenylacetaldoxime and N-(beta-phenylethyl)-hydroxylamine was mistaken for phenylacetaldimine and the compound erroneously described as the hydrated trimer of the aldimine, was actually the hydroxylamine derivative.
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19. It is also quite possible that the reduction may occur via a 1,4-addition especially in view of the polarity of the nitro group and of the fact that the reduction takes place at -40 to -50°C. It was reported
4 that the reduction of the double bond of cinnamyl alcohol proceeds slowly at room temperature after the rapid interaction of the polar alcoholic group with the hydride.
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Patent DE362714
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