There has been an increasing interest in the conversion of biomass to biofuels, energy, and chemicals due to an increase in meeting environmental demands and price and decrease in the potential availability of crude oil. Among the biofuels postulated as viable alternatives due to their physicochemical characteristics is butanol. Given its high energy content, it is projected as a potential substitute for ordinary gasoline. However, butanol production process through fermentation of lignocellulosic material has shown some disadvantages. Another way of producing butanol is by reduction of volatile fatty acids (from waste streams of organic matters) with hydrogen. An effluent with a high content of water and butanol is obtained. In that sense, thermodynamic interactions make the separation process challenging. On the other hand, current policies and needs have guided the proposals for chemical processes to meet various sustainability metrics, for example, high profit margins and low environmental impact, with inherent safety and robust operation in the presence of disturbances. With this in mind, this work proposes purification schemes to obtain butanol of high purity, from a butanol–water mixture, in the compositions generated by reduction of volatile fatty acids, using pervaporation, pressure swing distillation, and azeotropic distillation. Comparing the results obtained, the pervaporation scheme turned out to be the most promising alternative as it presents reductions in all the “green” indicators (compared to the other purification alternatives) in percentages between 27 and 52%. The general indices for such alternative were 0.0392 ($/kgbutanol), 0.0066 (ecopoints/kgbutanol), 8274, 2.772 × 10–04 (probability/year), and 0.4281 $/kgbutanol regarding the total annual cost, ecological indicator 99, condition number, individual risk, and minimum selling price, respectively.