Publication Date:
2011-10-06
Description:
Previously we reported that direct zincation of N , N -dimethylaniline by the mixed-metal zincate reagent 1 ((TMEDA)Na(TMP)( t -Bu)Zn( t -Bu)) surprisingly led to meta -metallation (zincation) of the aniline, as manifested in the crystalline complex 2 ((TMEDA)Na(TMP)( m -C 6 H 4 -NMe 2 )Zn( t -Bu)), and that iodination of these isolated crystals produced the meta -isomer N , N -dimethyl-3-iodoaniline quantitatively. Completing the study here we find that treating the reaction solution with iodine produces a 72% conversion and results in a mixture of regioisomers of N , N -dimethyliodoaniline, with the meta -isomer still the major product ( ortho : meta : para ratio, 6:73:21), as determined by NMR. In contrast to this bimetallic method, sodiation of N , N -dimethylaniline with n -BuNa produced the dimeric, ortho -sodiated complex 3 (((TMEDA)Na( o -C 6 H 4 -NMe 2 )) 2 ), as characterised by X-ray crystallography and NMR. No regioisomers were observed in the reaction solution. Introducing t -Bu 2 Zn to this reaction solution afforded a cocrystalline product in the solid-state, composed of the bis-anilide 4 ((TMEDA)Na( o -C 6 H 4 -NMe 2 ) 2 Zn( t -Bu)) and the Me 2 N–C cleavage product 5 ({(TMEDA) 2 Na} + {( t -Bu 2 Zn) 2 (µ-NMe 2 )} − ), which was characterised by X-ray crystallography. NMR studies of the reaction mixture that produces 4 and 5 revealed one additional species, but the mixture as a whole contained only ortho -species and a trace amount of para -species as established by iodine quenching. In an indirect variation of the bimetallic reaction, TMP(H) was added at room temperature to the reaction mixture that afforded 4 and 5 . This gave the crystalline product 6 ((TMEDA)Na(TMP)( o -C 6 H 4 -NMe 2 )Zn( t -Bu)), the ortho -isomer of the meta -complex 2 , as determined from X-ray crystallographic and NMR data. Monitoring the regioselectivity of the reaction by iodination revealed a 16.6:1.6:1.0 ortho : meta : para ratio. Interestingly, when the TMP(H) containing solution was heated under reflux for 18 hours more meta -isomer was produced (corresponding ratio 3.7:4.2:1.0). It is likely that this change has its origin in a retro reaction that produces the original base 1 as an intermediate. Theoretical calculations at the DFT level using the B3LYP method and the 6-311G** basis set were used to probe the energetics of both monometallic and bimetallic systems. In accord with the experimental results, it was found that ortho -metallation was favoured by sodiation; whereas meta - (closely followed by para -) metallation was favoured by direct sodium-mediated zincation. Beilstein J. Org. Chem. 2011, 7, 1234–1248. doi:10.3762/bjoc.7.144
Keywords:
alkali metalcrystal structureisomerisationmetallationzincation
Electronic ISSN:
1860-5397
Topics:
Chemistry and Pharmacology
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