2-Methylbenzoic acid → 4-Bromo-2-methylbenzoic acid

HRID 894162Notes

Reaction equation

HRID 894162 reaction equation
C(C1C=CC2COC3C=CC=CC=3C(=O)C=2C=1)#N.[C:19]1([CH3:28])[C:20]([C:25]([OH:27])=[O:26])=[CH:21][CH:22]=[CH:23][CH:24]=1.[Br:29]Br>[Fe]>[Br:29][C:23]1[CH:24]=[C:19]([CH3:28])[C:20]([C:25]([OH:27])=[O:26])=[CH:21][CH:22]=1

Participants

5

Reactant 3

HCID 83732-Methylbenzoic acidHCID 24408BromineHCID 129291409-Cyano-6,11-dihydro-11-oxodibenz[b,e]oxepin

Product 1

HCID 995704-Bromo-2-methylbenzoic acid

Reagents, catalysts & solvents 1

HCID 23925IronCatalyst

Procedure

9-Cyano-6,11-dihydro-11-oxodibenz[b,e]oxepin (IIA) may be prepared according to the following general reaction scheme: ##STR5## wherein R2 and R3 are as previously defined, by reacting o-toluic acid with bromine in the presence of iron powder in order to obtain 5-bromo-o-toluic acid. The product obtained from the reaction mixture is predominately the desired 5-bromo isomer although some 3-bromo isomer may be present. If desired, pure 5-bromo isomer can be separated by conventional techniques and employed in pure form as the starting material for subsequent steps. Separation, however, is unnecessary and the product obtained from the reaction mixture usually is employed in the next step without further purification. The 5-bromo acid then is treated with methanol (or any desired lower alkanol) in the presence of a strong acid such as sulfuric acid to form methyl (or lower alkyl) ester which then is treated with N-bromosuccinimide in the presence of benzoyl peroxide under reflux to form methyl (or lower alkyl) α,5-dibromo-o-toluate. The dibromo ester then is reacted with an appropriately substituted R2 and/or R3 phenol in the presence of dimethylformamide and potassium carbonate to obtain the corresponding methyl (or lower alkyl) 5-bromo-α-(R2 and/or R3 substituted phenoxy)-o-toluate. Hydrolysis of the ester with methanol and solium hydroxide yields, on acidification, the free acid when is cyclized in the presence of trifluoroacetic anhydride and boron trifluoride-ethyl ether complex to form the corresponding 9-bromo-6,11-dihydro-11-oxodibenz[b,e]oxepin. The cyano group is introduced as previously described by treating the 9-bromo compound with cuprous cyanide in the presence of dimethylformamide in order to obtain the desired R2 and/or R3 substituted 9-cyano-6,11-dihydro-11-oxodibenz[b,e]oxepin of formula IIA.

Workup

  1. customaccording to the following general reaction scheme

Sources & evidence

ORD record
ord-41ca63a57cf14f6382fd60bbc31657ec
Source dataset
uspto-grants-1981_08
Patent number
US04282365

Reaction notes

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