Ring bromination

A white solid, m.p. 178 C. Primarily of interest as a brominaling agent which will replace activated hydrogen atoms in benzylic or allylic positions, and also those on a carbon atom a to a carbonyl group. Activating influences can produce nuclear substitution in a benzene ring and certain heterocyclic compounds also used in the oxidation of secondary alcohols to ketones. 

Copper 1) chloride, bromide and cyanide were used by Sandmeyer to introduce a chlorine, a bromine atom and a cyanide group respectively into a benzene ring by addition to the phenyl diazonium salt. 

A point in case is provided by the bromination of various monosubstituted benzene derivatives it was realized that substituents with atoms carrying free electron pairs bonded directly to the benzene ring (OH, NH2, etc) gave 0- and p-substituted benzene derivatives. Furthermore, in all cases except of the halogen atoms the reaction rates were higher than with unsubstituted benzene. On the other hand, substituents with double bonds in conjugation with the benzene ring (NO2, CHO, etc.) decreased reaction rates and provided m-substituted benzene derivatives. 

One of the characteristic properties of phenol is the ease with which it gives substitution products, this property being particularly well shown by the ready nitration, sulphonation and bromination which the benzene ring in the phenol molecule undergoes. 

Bromobenzene is a colourless liquid of b.p. 156°, and d, 1 50 it has a faint agreeable odour. The bromine atom, being directly joined to the benzene ring, is very inert, and the only common reactions in which it is split off from the ring are the Fittig reaction (p. 288) and the Grignard reagent (pp. 280-284). 

These little beauties are like bromine quarterbacks in that they take the ball (Br) and hand it off to the receiver (1,3-benzodioxole). The great thing about these two species is that they are so bulky that the only place on the benzene ring that they can hand off their Br atom with any efficiency is at the least hindered 5 carbon... 

Within the cubane synthesis the initially produced cyclobutadiene moiety (see p. 329) is only stable as an iron(O) complex (M. Avram, 1964 G.F. Emerson, 1965 M.P. Cava, 1967). When this complex is destroyed by oxidation with cerium(lV) in the presence of a dienophilic quinone derivative, the cycloaddition takes place immediately. Irradiation leads to a further cyclobutane ring closure. The cubane synthesis also exemplifies another general approach to cyclobutane derivatives. This starts with cyclopentanone or cyclohexane-dione derivatives which are brominated and treated with strong base. A Favorskii rearrangement then leads to ring contraction (J.C. Barborak, 1966). 

Synthesis of (A) started with the combination of 2,4,6-trimethylphenol and allyl bromide to give the or/Ao-allyl dienone. Acid-catalyzed rearrangement and oxidative bydroboration yielded the dienone with a propanol group in porlactone ring were irons in the product as expected (see p. 275). Treatment with aqueous potassium hydroxide gave the epoxy acid, which formed a crystalline salt with (R)-l-(or-naphthyl)ethylamine. This was recrystallized to constant rotation. 

Another method for the hydrogenoiysis of aryl bromides and iodides is to use MeONa[696], The removal of chlorine and bromine from benzene rings is possible with MeOH under basic conditions by use of dippp as a ligand[697]. The reduction is explained by the formation of the phenylpalladium methoxide 812, which undergoes elimination of /i-hydrogen to form benzene, and MeOH is oxidized to formaldehyde. Based on this mechanistic consideration, reaction of alcohols with aryl halides has another application. For example, cyclohex-anol (813) is oxidized smoothly to cyclohexanone with bromobenzene under basic conditions[698]. 

The reaction of 2-amino-4(2-furyl)thiazole in acetic acid with bromine yields product 198 brominated on the furan ring (Scheme 126). The... 

Bromination occurs on the 5-positton of the ring the bromo compound... 

When unsubstituted, C-5 reacts with electrophilic reagents. Thus phosphorus pentachloride chlorinates the ring (36, 235). A hydroxy group in the 2-position activates the ring towards this reaction. 4-Methylthiazole does not react with bromine in chloroform (201, 236), whereas under the same conditions the 2-hydroxy analog reacts (55. 237-239. 557). Activation of C-5 works also for sulfonation (201. 236), nitration (201. 236. 237), Friede 1-Crafts reactions (201, 236, 237, 240-242), and acylation (243). However, iodination fails (201. 236). and the Gatterman or Reimer-Tieman reactions yield only small amounts of 4-methyl-5-carboxy-A-4-thiazoline-2-one. Recent kinetic investigations show that 2-thiazolones are nitrated via a free base mechanism. A 2-oxo substituent increases the rate of nitration at the 5-position by a factor of 9 log... 

The chief reason why ethylenebromonium ion m spite of its strained three membered ring IS more stable than 2 bromoethyl cation is that both carbons and bromine have octets of electrons whereas one carbon has only six electrons m the carbocation... 

This suggests that as water attacks the bromonium ion positive charge develops on the carbon from which the bromine departs The transition state has some of the character of a carbocation We know that more substituted carbocations are more stable than less substituted ones therefore when the bromonium ion ring opens it does so by breaking the bond between bromine and the more substituted carbon... 

Aluminum chloride is a stronger Lewis acid than iron(lll) bromide and has been used as a catalyst in electrophilic bromination when as in the example shown the aromatic ring bears a strongly deactivating substituent... 

Electrophilic aromatic substitution (Sec tion 22 14) Arylamines are very reac tive toward electrophilic aromatic sub stitution It IS customary to protect arylamines as their N acyl derivatives before carrying out ring nitration chio rination bromination sulfonation or Friedel-Crafts reactions... 

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