Exposure to benzene, which has been linked to acute myeloid leukemia and non-Hodgkin's lymphoma, is a continuing problem for the chemical industry. The most effective way of dealing with benzene's human health risk is to eliminate its use. Such a far-reaching solution requires the elaboration of fundamentally new syntheses for chemicals derived from benzene. Along these lines (Scheme 1), we have elaborated syntheses of phenol,1 catechol, hydroquinone,2 pyrogallol,3 hydroxyhydroquinone,4 adipic acid 5 and caprolactam where benzene is replaced as a starting material with nontoxic glucose. Considerable research activity is currently being focused on elaboration of syntheses of phloroglucinol and resorcinol from glucose.

Scheme 1

Our benzene-free synthetic routes typically entail microbial synthesis of an intermediate followed by chemical conversion of this intermediate into the desired product. Examples of this strategy are found in our syntheses of phenol1 and hydroquinone,2 which are highly toxic to microbes. The microbial toxicity of phenol is circumvented by high-yielding microbial synthesis of nontoxic shikimic acid, which can be accomplished using recombinant strains cloned in our group (Scheme 2). 6, 7, 8 Shikimic acid is then heated in near-critical water to afford phenol (Scheme 2).1 Synthesis of hydroquinone begins with the high-yielding microbial synthesis of quinic acid using a recombinant strain cloned in our group (Scheme 2).2 Nontoxic quinic acid is then chemically converted into hydroquinone (Scheme 2). The chemical methodology employs either NaOCl, which is arguably the world's cheapest stoichiometric oxidant, or catalytic amounts of Ag+1 with K2S2O8 serving as the cooxidant.2

Scheme 2


(a),(b),(c),(d) recombinant microbes; (e) H2O, 350 °C; (f) NaOCl or Ag+1/K2S2O8; (g) chemical deamination/cyclization; H2, Pt on C.

Synthesis of bionylon has been another research goal. The nylon market is dominated by nylon 66 and nylon 6, which are respectively produced from adipic acid and caprolactam. Global production of adipic acid is approximately 2.0 x 109 kg/yr. Our synthesis of adipic acid (Scheme 2) begins with the construction and use of a recombinant microbe that catalyzes the conversion of glucose into cis,cis-muconic acid.5 Hydrogenation of cis,cis-muconic acid affords adipic acid in quantitative yield (Scheme 2).5 Global production of caprolactam is approximately 3.6 x 109 kg/yr. Improvements in the yield of L-lysine microbially synthesized from glucose coupled with the increased demand for this amino acid suggest that L-lysine could be an attractive starting material for production of caprolactam. Using synthetic organic methodology developed in our group, we are currently achieving a 60% (mol/mol) yield of sublimed caprolactam from L-lysine (Scheme 2).

In addition to its problematic toxicity, benzene contributes significantly to the profitability of petroleum production and refining. The majority of the petroleum used by the United States is now imported and leads to geopolitical problems. Specifically, reliance on politically unstable countries for petroleum imports has played a significant role in the rise and spread of anti-American fervor and global terrorism. By contrast, glucose is derived from renewable starch and cellulose, which are produced in great abundance in the United States. Starch and cellulose are also essentially immobilized CO2. As a consequence, synthesis of chemicals, particularly large-volume commodity chemicals, from glucose is essentially a method for immobilization of atmospheric CO2. Such a credit, even if initially modest, may be critical as the United States belatedly struggles to meet national CO2 budgets set by international treaty.