Benzene reaction with acetyl chloride

TTie true ketones, in which the >CO group is in the side chain, the most common examples being acetophenone or methyl phenyl ketone, C HjCOCH, and benzophenone or diphenyl ketone, C HjCOC(Hj. These ketones are usually prepared by a modification of the Friedel-Crafts reaction, an aromatic hydrocarbon being treated with an acyl chloride (either aliphatic or aromatic) in the presence of aluminium chloride. Thus benzene reacts with acetyl chloride... 

Reduction of a nitro compound to a primary amine. In a 50 ml. round-bottomed or conical flask fitted with a reflux condenser, place 1 g. of the nitro compound and 2 g. of granulated tin. Measure out 10 ml. of concentrated hydrochloric acid and add it in three equal portions to the mixtiue shake thoroughly after each addition. When the vigorous reaction subsides, heat under reflux on a water bath until the nitro compound has completely reacted (20-30 minutes). Shake the reaction mixture from time to time if the nitro compound appears to be very insoluble, add 5 ml. of alcohol. Cool the reaction mixture, and add 20-40 per cent, sodium hydroxide solution imtil the precipitate of tin hydroxide dissolves. Extract the resulting amine from the cooled solution with ether, and remove the ether by distillation. Examine the residue with regard to its solubility in 5 per cent, hydrochloric acid and its reaction with acetyl chloride or benzene-sulphonyl chloride. 

Using 1,2-dichloroethane as solvent, Brown et al. 16 have also studied the acetylation reaction, with acetyl chloride and aluminium chloride as reagents at 25 °C. The appropriate data for benzene are given in Table 111 and by comparison with Table 109 it appears that acetylation occurs some 300 times as fast as benzoylation. 

A benzofuran ring replaces one of the benzene rings of the biphenyl moiety present in many of the sartans in the rather more complex drug saprisartan (80-10). It is of note, further, that the acidic proton is provided in this case by a trifluorosulfo-namide instead of the more common tetrazole ring. Construction of the imidazole fragment begins by nitrosation of the (3-ketoester (79-1) by means of sodium nitrite in acid to afford the oxime (79-2). Reaction with acetyl chloride leads to the ester (79-3). Reaction of this last intermediate with the iminoether from propionitrile then affords the imidazole (79-4). 

Quinoxaline 1,4-dioxide undergoes reaction with acetyl chloride and substitution occurs in the benzene ring to give 6-chloroquinoxaline 1 -oxide and, on increasing the reaction time, 3-chloroquinoxaline 1-oxide and 6,7-dichloroquinoxaline appear as additional products.A similar reaction is observed with 3-phenylquinoxalin-2(l//)-one 4-oxide and its 7-substituted derivatives, where ring substitution at position 6 again is accompanied by deoxygenation. 2-Chloroquinoxalinc 1-oxide (19) is obtained in 60% yield by treatment of quinoxaline 1,4-dioxide with benzenesulfony chloride and consequent neutralization of the benzenesulfonate initially formed,and in addition about 3% of 3-chloroquinoxaline 1-oxide is formed. 

Now let s draw the forward scheme. Benzene is converted into chlorobenzene upon treatment with CI2 and AICI3 (via an electrophilic aromatic substitution reaction). Chlorobenzene is then converted to aniline via an elimination-addition reaction. Reaction with acetyl chloride (in the presence of pyridine) converts aniline to the desired amide. 

Partial rate factors may be used to estimate product distributions in disubstituted benzene derivatives. The reactivity of a particular position in o-bromotoluene, for example, is given by the product of the partial rate factors for the corresponding position in toluene and bromobenzene. On the basis of the partial rate factor data given here for Friedel-Crafts acylation, predict the major product of the reaction of o-bromotoluene with acetyl chloride and aluminum chloride. 

Just as an aromatic ring is alkylated by reaction with an alkyl chloride, it is acylated by reaction with a carboxylic acid chloride, RCOC1, in the presence of AICI3. That is, an acyl group (-COR pronounced a-sil) is substituted onto the aromatic ring. For example, reaction of benzene with acetyl chloride yields the ketone, acetophenone. 

This procedure is a modification of preparations of 3-phen)d, sydnone described earlier. The dehydration of N-nitroso-N phenylglycine has also been effected by the use of thionyl chloride and pyridine in dioxane, thionyl chloride in ethertrifluoroacetic anhydride in etherand diisopropylcarbodiimide in water or by reaction of the alkali metal salts of N-nitroso-N-phenylglycine with phosgene or benzenesulfonyl chloride in water or with acetyl chloride in benzene. ... 

The frustrating and sometimes capricious nature of simple reactions of 2-amino-4(5H)-oxazolones is exemplified in the following reports. Ramsh and co-workers acetylated 68 with acetyl chloride in benzene but isolated both a poor yield and a poor mass balance of 131 together with dehydroacetic acid 132. Attempts to transaminate 131 with diethylamine in the absence of a solvent or with aniline in benzene failed. The authors recovered 68, which is in stark contrast to an earlier report from Hansen and Masch that acetylation of 68 with acetic anhydride gave 131 in 87% yield. In addition, these same authors reported that reaction of 131 with diethylamine at room temperature gave 134 in excellent yield (Scheme 6.35). 

Solid Catalysts. Nafion-H is an active catalyst for acylation with aroyl halides and anhydrides.60,61 The reaction is carried out at the boiling point of the aromatic hydrocarbons. Yields with benzoyl chloride using 10-30% Nafion-H for benzene, toluene, and p-xylene are 14%, 85% and 82%, respectively. Attempted acylation with acetyl chloride, however, led to HC1 evolution and ketene formation. Nation resin-silica nanocomposite materials containing a dispersed form of the resin within silica exhibits significantly enhanced activity in Friedel-Crafts acylations.62,63... 

The oxygen of ketone and aldehyde groups is readily replaced by halogen under the influence of phosphorus trichloride or pentachloride the reaction may be carried out with or without a solvent solvents commonly employed are chloroform, benzene, petroleum ether, acetyl chloride and phosphorus oxychloride. 

Acyl chlorides were also tested in acylations promoted by B(OTf)3.231 Acylation of benzene and toluene in competitive reactions (molar ratio = 5 1) with acetyl chloride shows high para selectivity (92-95% with 2.5-7% of meta, kT/kB — 31-73), whereas the para isomer is formed only with 72-75% selectivity (8-10% of meta, k lkK = 78) in benzoylation with benzoyl chloride. Acetylation appears not to be affected by significant isomerization as indicated by isomer distributions and relative reactivity data. 

Ferrocene reacts with acetyl chloride and aluminum chloride to afford the acylated product (287) (Scheme 84). The Friedel-Crafts acylation of (284) is about 3.3 x 10 times faster than that of benzene. Use of these conditions it is difficult to avoid the formation of a disubstituted product unless only a stoichiometric amount of AlCft is used. Thus, while the acyl substituent present in (287) is somewhat deactivating, the relative rate of acylation of (287) is still rapid (1.9 x 10 faster than benzene). Formation of the diacylated product may be avoided by use of acetic anhydride and BF3-Et20. Electrophilic substitution of (284) under Vilsmeyer formylation, Maimich aminomethylation, or acetoxymercuration conditions gives (288), (289), and (290/291), respectively, in good yields. Racemic amine (289) (also available in two steps from (287)) is readily resolved, providing the classic entry to enantiomerically pure ferrocene derivatives that possess central chirality and/or planar chirality. Friedel Crafts alkylation of (284) proceeds with the formation of a mixture of mono- and polyalkyl-substituted ferrocenes. The reaction of (284) with other... 

For the reaction of acetyl chloride with benzene, it was determined that the rate at which acetophenone was produced was dependent on the Lewis acidity of the ionic liquid, which in turn depends on the ionic liquid composition. For example, in the acidic composition described by equation 2, [AI2CI7]" reacts with the reagent to generate the electrophile according to equation 4. ... 

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