2-Bromoacetophenone, reaction

Nuclear halogenation of acetophenone depends on formation of the aluminum chloride complex. If less than one equivalent of aluminum chloride is used, side-chain halogenation occurs. 3-Bromoacetophenone has been prepared from 3-aminoaceto-phenone by the Sandmeyer reaction. The synthesis described here has been taken from work of the submitters, who have used it to prepare many 3-bromo- and 3-chloroacetophenones and benzaldehydes, as well as more highly halogenated ones (Notes 7 and 8). 

Besides acetophenone, this reaction was also applied to p-methoxy-and p-bromoacetophenone, but in all cases yields are low. 

R = Ar) and cyclized tricyclic compound 240 (R = Ar) was obtained when 2-bromoacetophenones were reacted with 8-hydroxyquinolin-2(l//)-one under the above conditions. Presence of a 4-methoxy substituent shifted the equilibrium to the ring-opened product 241 (R = 4-MeOPh), while that of 4-nitro group gave only cyclized product 240 (R = N02). Similarly, mixtures of ring-opened and 2,3,6,7-tetrahydro-5//-pyrido[l,2,3- /e]-l,4-benzoxazin-5-one derivatives were formed in the reaction of 8-hydroxy-l,2,3,4-tetrahydroquinolin-2-one and halomethyl ketones (00HCA349). 

Problem 19.4 How would you carry out the following reactions More than one step may be required, (a) 3-Hexvne 3-Hexanone, (b) Benzene —> m-Bromoacetophenone I (c) Bromobenzene —> Acetophenone (d) 1-Methylcyclohexene — 2-Methylcyclohexanone... 

Remarkably, one year later Leadbeater described that biaryls can be synthesized via a Suzuki-type coupling under transition-metal free conditions [51, 52]. The reaction conditions were almost identical to those reported for the ligand-free process, with the difference being that a larger amoimt of Na2C03 and arylboronic acid were used. Only one successful example of a heteroaryl haUde substrate is shown namely, the coupling of 2-bromopyridine with phenylboronic acid (Scheme 32). 3-Bromothiophene did not couple under the same reaction conditions. Unfortimately, attempts to use heteroarylboronic acids such as 3-pyridinylboronic acid, 3-thienylboronic acid, and lH-indol-5-ylboronic acid on 4-bromoacetophenone completely failed. 

The SET mechanism is chiefly found where X = I or NO2 (see 10-104). A closely related mechanism, the SrnE takes place with aromatic substrates (Chapter 13). In that mechanism the initial attack is by an electron donor, rather than a nucleophile. The Srn 1 mechanism has also been invoked for reactions of enolate anions with 2-iodobicyclo[4.1.0]heptane. An example is the reaction of l-iodobicyclo[2.2.1]-heptane (15) with NaSnMe3 or LiPPh2, and some other nucleophiles, to give the substitution product. Another is the reaction of bromo 4-bromoacetophenone (16) with Bu4NBr in cumene. " The two mechanisms, Sn2 versus SET have been compared and contrasted. There are also reactions where it is reported that radical, carbanion, and carbene pathways occur simultaneously. ... 

When Sn2 reactions are carried out on these substrates, rates are greatly increased for certain nucleophiles (e.g., halide or halide-like ions), but decreased or essentially unaffected by others. For example, a-Chloroaceto-phenone (PhCOCH2Cl) reacts with KI in acetone at 75°C 32,000 times faster than l-Chlorobutane, ° but a-bromoacetophenone reacts with the nucleophile triethylamine 0.14 times as fast as iodomethane. The reasons for this varying behavior are not clear, but those nucleophiles that form a tight transition state (one in which bond making and bond breaking have proceeded to about the same extent) are more likely to accelerate the reac-tion. ... 

It was possible to effect lOOC reaction leading to six-membered rings, e.g., 220 in low yield (ca. 20%) by heating the reaction mixture at 110 °C (Eq. 22) [59]. In fact, Oppolzer and Keller [60] had previously reported the lOOC reaction of 219 to 220 in 20% yield by heating at 110 °C. Furthermore, the scope of these oxime-olefin cycloadditions has been extended to ketoximes, e.g., 221. The latter was prepared by amination of a-bromoacetophenone with allylamine 214a. Heating of 221 at 110 °C for 8 h led to cycloaddition with formation of the fused pyrrolidine 222 in 88% yield. As in Scheme 25, only one... 

As a second example, several Hantzsch syntheses using diverse ring-substituted 2-bromoacetophenones and 1-substituted-2-thioureas are given. For these reactions, comparative and better yields were achieved when using a micro-mixing tee chip reactor as compared with conventional laboratory batch technology. The increase in yield amounted to about 10-20% [156, 157]. 

Linear and angular thiazolothienopyridines have been synthesized from the thiazolopyridinethione 105, by reaction with bromoacetophenone 106 to give the linear product 107, or sulfur and triethylamine to give the angular fused tricycle 104 (Scheme 7) <2003JCCS1061>. 

In some cases, this reaction is much more complicated. 5-Substituted-l,3,4-oxadiazoline-2-thiones when alkylated with tu-bromoacetophenones afforded products that might result either from the initial attack of the electrophile on sulfur or on nitrogen (Equation 3) <2001RJC1754>. 

The synthesis of 1,3-selenazoles from A -phenylimidoyl isoselenocyanates has been reported. N-phenylimidoyl isoselenocyanates 94 are prepared from N-phenylbenzamides 92. Treatment of 92 with thionyl chloride affords N-phenylbenzimidoyl chlorides 93, which yield imidoyl isoselenocyanates 94 on reaction with potassium isoselenocyanate. The imidoyl isoselenocyanates 94 were transformed into selenoureas 95 with either ammonia or primary or secondary amines. Reaction of 95 with an activated bromomethylene compound such as bromoacetophenone in the prescence of a base gave the 1,3-selenazole 97 via the salt 96 <00HCA1576>. 

The preparation of 2-amino-5-arylselenazoles 99 and 3,5-diaryl-1,2,4-selenadiazoles 101 has been described. Starting from readily available a-arylsulfonyl-a-bromoacetophenones 98 reaction with selenourea gave 2-amino-5-arylselenazoles 99 in good yield. Reaction of 98 with selenobenzamide 100 did not give the expected selenazole the 3,5-diaryl-1,2,4-selenadiazole 101 was obtained in moderate yield. Compound 101 is a known oxidation product of selenobenzamide and a mechanism for its formation is proposed <99JHC901>. 

Bromine, reaction with furan in methanol to yield 2,5-dimethoxy-2,5-dihydrofuran, 40, 29 3-Bromoacetophenone, 40, 7... 

The reaction of 2-amino-6-phcnylimidazo[2,l - [ l, 3,4 thiadiazolc 160 <1967ZC341> with 2-bromoacetophenone gives the corresponding salt 14 (Equation 2) <2002ARK32>. 

It is noteworthy that, although 4-bromoanisole produces anisic acid in high yield, 4-hydroxybenzoic acid is isolated in only 17% yield from the corresponding reaction of 4-bromophenol. Also, 4-bromoacetophenone, which may react by a normal SN reaction, is readily converted into 4-acetylbenzoic acid, whereas 4-bromonitro-benzene produces 4-nitrobenzoic acid in only 17% yield, together with nitrobenzene (17%). 

Jegou and Jenekhe [63] have developed a different approach toward di-ethynylated quinoline monomers, as shown in Scheme 10. Reaction of 2-amino-5-bromobenzophenone with 4-bromoacetophenone gave 6-bromo-2-(4 -bro-mophenyl)-4-phenylquinoline, which was alkynylated and deprotected ac-... 

Reduction of co-bromoacetophenone in aprotic solvents leads to acetophenone enolate. This is trapped by reaction with a second molecule of substrate to yield... 

A butoxylcarbonylation reaction was conducted in a liquid-liquid biphasic system under process conditions, but the removal of the product was conducted in a liquid-solid biphasic system at a lower temperature (84). lodobenzene or 4-bromoacetophenone reacted with CO at a pressure of 1-8 atm in the presence of a palladium-benzothiazole complex catalyst in the ionic liquid [TBA]Br (m.p. = 110°C) in the presence of Et3N base. The catalyst/ionic liquid system was recycled by extractive removal of the butyl ester product with diethyl ether. The solid residue, containing the catalyst, [TBA]Br, and Et3N.HBr, remained effective in subsequent carbonylation tests. After each cycle, the yields were still close to the initial value. A slight decrease in yield was attributed to a loss of catalyst during handling. 

In the middle of the 1950s, Knott reported the synthesis of dyesmffs based on benzothiazole derivatives. Alkylation of Al-methylbenzo-l,3-thiazole-2-thione with a-bromoacetophenone and deprotonation of the resulting thiocarbonylium salt 5 yielded, after spontaneous desulfurization of the intermediate thiirane (7), the alkylidene derivative 8 (18) (Scheme 5.1). In order to rationalize the reaction, thiocarbonyl ylide 6 was proposed as the precursor of thiirane 7. To the best of our... 

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