A-Bromopropiophenone

Bupropion The synthesis of bupropion, I-3(-chlorophenyl)-2-[(I,I-dimethyIethyl)amino]-I-propanone (7.3.5), begins with the reaction of 3-chlorobenzonitriIe, with ethylmagnesium bromide to give 3-chloropropiophenone (7.3.3). Brominating this with bromine gives 3-chloro-a-bromopropiophenone (7.3.4), which on reaction with tert-butylamine gives bupropion (7.3.5) [54-58]. 

Diethylpropion Diethylpropion, l-phenyl-2-diethylaminopropanon (8.3.6), is synthesized by the bromination of propiophenone into a-bromopropiophenone (8.3.5) and the subsequent substitution of the bromine atom with a diethylamino group [25,26]. 

It is synthesized from 4-benzyloxypropiophenone, which undergoes bromination into 4-benzyloxy-a-bromopropiophenone (11.1.17). This is reacted with 2-(4-benzy-loxyphenyl)ethylamine, forming an intermediate product (11.1.18), which undergoes fnrther debenzylation by hydrogen nsing a palladium catalyst, giving ritodrine (11.1.19) [24,25]. 

The p-benzoxy-a-bromopropiophenone and l-phenyl-3-amino-butane were heating for an hour on the water bath in the absence of solvents. A solid crystalline cake was obtained. After being extracted with boiling acetic acid, the hydrobromide of l-(p-hydroxyphenyl)-2-(p-phenylbutylamino)propanone-l was obtained. 

In methylene chloride (3 L) was dissolved m-chloropropiophenone (698.0 g 4.15 mole). The solution was stirred with charcoal (Darco) and magnesium sulfate for 2 h and filtered. To it was added with stirring (662.0 g) of bromine in methylene chloride (1 L). When the bromine color had faded completely, the solvent was evaporated in vacuum and m-chloro-a-bromopropiophenone was obtained as oil. 

The m-chloro-a-bromopropiophenone was dissolved in acetonitrile (1300 ml). To this, t-butylamine (733.0 g) in acetonitrile (1300 ml) was added while keeping the temperature below 32°C. The reaction mixture was allowed to stand over night. It was then partitioned between water (4200 ml) and ether (2700 ml). The aqueous layer was extracted with a further portion of ether (1300 ml). The combined ethereal layers were then washed with water (4200 ml) to which hydrochloric acid was added until the pH of the aqueous layer was 9. The aqueous layer was separated and washed with ether (500 ml) and then discarded. The combined ethereal layers were then stirred with ice (560.0 g) and concentrated hydrochloric acid (324 ml). The ethereal layer was separated and again washed with water (200 ml) and concentrated hydrochloric acid (50 ml). These last two acid layers were combined and concentrated in vacuum until crystals appeared. The solution was then chilled to 5°C and filtered. The product was sucked dry, washed with acetone and recrystallized from a mixture of isopropanol (3 L) and absolute ethanol (800 ml). The DL-m-chloro-a-t-butylaminopropiophenone hydrochloride so was obtained, melting point 233°-234°C. 

The starting material is produced by reacting propiophenone with bromine and then reacting the a-bromopropiophenone produced with 2-methylaminomethanol. 

Reduction of oj.-bromoacetophenone gave the corresponding bromo-hydrin in 85% yield.6 Smooth reduction, also occurred with chloral2-16 and bromal.6 However, a-bromopropiophenone 44 gave only 35 to 42% yields of the bromohydrin the remainder of the product was halogen-free, consisting of a mixture of benzylmethylcarbinol and some ethers. 

Advantages over the other methods ate not obvious, and the method is not applicable to other a-halo-carbonyl compounds such as 2-chlorocyclohexanone and a-bromopropiophenone. 

It is difficult to stop this reaction after the addition of one Br atom because the electron-withdrawing inductive effect of Br. stabilizes the second enolate. As a result, the a H of a-bromopropiophenone is more acidic than the a H atoms of propiophenone, making it easier to remove with base. 

A solution of benzamidine hydrochloride dihydrate (48 g, 0.25 mol) in water (100 ml) is added to a solution of a-bromopropiophenone (53 g, 0.25 mol) in chloroform (250 ml) to form a two-phase mixture. While stirring vigorously at room temperature, a solution of KOH (28 g, 0.5 mol) in water (100 ml) is added dropwise, then heated to boiling and refluxed (3-4h). The chloroform phase is then separated from the hot aqueous phase and cooled. Tlie ciwstalline material which separates is washed with benzene, then with diethyl ether to give the above product (which may separate as an oil, but which solidifies gradually on addition of benzene). Ilie yield is in the range 26-32 g (45-55%), m.p. 214-215°C. Similarly prepared are 4-methyl-2,5-bis-(m-nitrophenyI)-(39%), 4-methyl-2,5-bis-(m-bromophenyl)- (40%), and 4-methyl-2,5-bis-(p-nitrophenyl)imidazolcs (64%). 

Of these products the main one was the carbinol LXII. A similar oxide intermediate explains the formation of benzylmethylcarbinol from a-bromopropiophenone. In addition to the ethers corresponding to these carbinols, there was also obtained the monoether of a glycol. This may have been formed from the intermediate oxide (LVI) by the addition of isopropyl alcohol to the oxide ring, or by diipct reaction of the bromo-hydrin (LV) with aluminum isopropoxide. Curiously enough, when the reduction was carried out at 33°, a-bromoisobutyrophenone gave a bromohydrocarbon as the main product. This was shown to be LXIII accompanied by some of its allylic isomer (LXIV). 

In DMF containing lithium perchlorate, reduction of o -bromopropiophenone at mercury gives l,4-diphenyl-2,3-dimethylbutan-l,4-dione in 65% yield [236]. However, electrolysis of a-bromopropiophenone in the presence of benzoyl chloride affords only l,3-diphenyl-2-methylpropan-l,3-dione. Other studies involving reduction of phenacyl bromides include the electrosynthesis of 4-aryl-2-methylfurans [237] and the regioselective synthesis of enol carbonates [238] semicarbazones of phenacyl bromide can be converted into 3,7-diaryl-2/7-imidazo[2,l-Z>][l,3,4]oxadiazines [239]. Reduction of 1,2-dibenzoyl-chloroethane at mercury in DMF containing lithium perchlorate affords mixtures of phenyl tribenzoyl cyclopentanols and diphenyl dibenzoyl butanediones [240]. 

In the present work, we have carried out the rearrangement of acetals of a-bromopropiophenone to 2-phenylpropanoates catalyzed by large pore zeolites containing Lewis metal ions. We have found that our results can be interpreted taking into account the Lewis nature of the active sites but also assuming that their softness-hardness is modified by the zeolite framework. 

Dimethyl acetals of a-bromopropiophenone and a-bromoacetophenone were synthesized by stirring at 323 K for 2 h a solution of the corresponding phenyl ketone... 

Aimed to explore the extent of these radical processes using our Lewis metal ion containing zeolites, we have treated the a-bromopropiophenone (2) in methanol/trimethyl orthoformate mixtures, which besides to be a better hydrogen donor medium than chlorobenzene and hence more propiophenone should be now expected, could shift the equilibrium to the acetal 1b formation. The results obtained... 

PhCOCH2SC(S)NMe2 is tranformed into the 1,3-oxathiolium salt (447) by treatment with dimethyl sulphate followed by sodium perchlorate.Monothio-benzil forms tetraphenyl-l,3-oxathiole (448) by the action of diazodiphenyl-methane.The thioamide (449) reacts with a-bromopropiophenone to yield the methyleneoxathiole (450). The action of pyridine hydrochloride on 5-(2-methoxyphenyl) AW-dimethylthiocarbamate results in the l,3-benzoxathiol-2-one (451). o-Benzoylbenzenesulphonyl chloride (452) exists as an equilibrium... 

Benzoaquinone Dobesilate calcium Ethamsylate Megestrol acetate Benzotetronic acid Ethyl biscoumacetate p-Benzoxy-a-bromopropiophenone Nylidrin... 

A Bischler-Mohlau indole synthesis was also used in constructing the indole ring of bazedoxifene acetate (Viviant), a novel and highly selective indole estrogen. It is a selective estrogen receptor modulator (SERM) for the treatment of and prevention of osteoporosis. Condensation between a-bromopropiophenone and 4-(benzyloxy)-aniline hydrochloride generated the 3-methyl indole core. ... 

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