[7632-51-1] · Cl4V · Vanadium(IV) Chloride · (MW 192.74)
(oxidative coupling of phenols)
Alternate Names: vanadium tetrachloride; tetrachlorovanadium; vanadium chloride.
Solubility: sol with decomposition in cold water; sol abs alcohol, ether, chloroform, acetone.
Form Supplied in: commercially available as a bright red liquid.
Handling, Storage, and Precautions: moisture sensitive; spills may be neutralized with water. Toxic and corrosive; use efficient fume hood and wear plastic-covered gloves and apron (attacks neoprene).1
The oxidation of a number of simple phenols and aniline derivatives by vanadium tetrachloride affords dimeric products which are predominantly the result of intermolecular coupling at the para position.2 For example, the addition of ca. 1 equiv of VCl4 to phenol in dry carbon tetrachloride generates, after isolation, an 8:4:1 mixture of 4,4´-, 2,4´-, and 2,2´-biphenols, respectively (eq 1). Virtually no change in yield is observed when the ratio of phenol to VCl4 is varied. While the related p- and m-cresol generate only polymeric products, o-cresol does dimerize to 3,3´-dimethyl-4-4´-dihydroxybiphenyl in 26% yield.2
Hindered phenols have been coupled with moderate success. For example, dimerization of 3,5-dimethoxyphenol to the corresponding para-para adduct 2,2´,6,6´-tetramethoxy-4,4´-dihydroxybiphenyl and its ortho-para isomer has been effected in 10.8% overall yield as a 4:1 ratio of the respective regioisomers (eq 2).1a The para-para coupled dimer is the key intermediate in the total synthesis of the algal metabolite fucophlorethol A. Similarly, 6-t-butyl-3-methylphenol undergoes VCl4-mediated coupling to a mixture of the para-para and the ortho-para products.3 The overall yield and regioisomeric ratio are improved by reducing the reaction temperature from 20 °C to 0 °C (eq 3).
Both 1- and 2-naphthols react cleanly to generate 4,4´- and 2,2´-dihydroxybinaphthyl in 40% and 38% yields, respectively.2 Benzene, toluene, anisole, phenyl acetate and ethyl benzoate are unreactive under standard reaction conditions. Although the attempted coupling of aniline generates little dimerized product, N,N-dimethylaniline yields N,N,N´,N´-tetramethylbenzidine in 52% yield.2 Generally, VCl4 complements the use of the less reactive Vanadyl Trichloride
When a diethyl ether/pentane solution of vanadium tetrachloride is treated sequentially with 3 equiv of lithium dialkylamide, 1 equiv of MeLi, and 0.8 equiv of an aromatic aldehyde, a one-pot reductive coupling reaction ensues, generating N,N,N´,N´-tetraalkyl-1,2-diarylethylenediamines4 in yields ranging between 14% and 54% (eq 4). The active reagent in this reaction is the in situ generated tris(dialkylamino)methylvanadium(IV). Addition of N-methylaniline to a solution of VCl4 affords an adduct which will effect the cyclization of nerol (1) to the corresponding terpinyl halide (2) (eq 5).5 The related TiX4 complex appears to be the preferred reagent in this type of reaction.
Michael K. O'Brien & Benoit Vanasse
Rhône-Poulenc Rorer Pharmaceuticals, Collegeville, PA, USA