Published: October 13, 2011 Copyright r 2011 American Chemical Society and Division of Chemical Education, Inc. 147 dx.doi.org/10.1021/ed100838a | J. Chem. Educ. 2012, 89, 147–149 LABORATORY EXPERIMENT pubs.acs.org/jchemeduc Synthesis of Two Local Anesthetics from Toluene: An Organic Multistep Synthesis in a Project-Oriented Laboratory Course Patricia Demare and Ignacio Regla* Facultad de Estudios Superiores-Zaragoza, Universidad Nacional Aut onoma de M exico, Batalla del 5 de Mayo esq. Fuerte de Loreto, Ej  ercito de Oriente, 09230 M exico, D.F., M exico b S Supporting Information O ur academic approach is based on the premise that learning is facilitated in a research environment, which involves independent study, decision making, and problem solving through research projects. 1À3 To this end, a nontraditional advanced undergraduate organic chemistry laboratory course was developed. The project-oriented system consists of half- semester research projects (about eight 4-h lab sessions) that involve the multistep synthesis of a variety of classical pharma- ceutical drugs, with methodologies usually adapted from primary literature. One of these projects is described; the multistep synthesis of two local anesthetic drugs, benzocaine and prilo- caine, from a common three-step sequence starting from toluene that requires the student to formulate a hypothesis and to design experiments to test it. ’ LABORATORY DYNAMICS Students work singly or in pairs, with different projects. Each instructor is in charge of up to 10 students. The semester work starts with three to five simple experiments, presented in a nonconventional laboratory manual (more accurately, a labora- tory guide) that includes: (i) an introduction describing the work system; (ii) 40 experimental proposals (each featuring a reaction scheme, main objective, procedure references, a study guide, prelab questions, and notes, as well as IR and NMR spectra); and (iii) 10 appendixes addressing topics such as the lab notebook, experimental design, microscale, waste disposal, bibliographic research, and laboratory rules (the original version of this manual, in Spanish, is included in the Supporting Information). Before conducting each experiment, students search for information, discuss it with the instructor, and outline a labora- tory work plan, generating a grade that will be averaged with the lab work and report. In this preliminary evaluation, the instructor inquires about the theoretical background of the experiment (reaction type, mechanism, stoichiometry, etc.) and the proce- dure, frequently advising students against the idea that they must “follow instructions step-by-step” to achieve success. This inter- action is intended to promote a critical process that allows students to design their own work plan and gives them self- confidence. The dialogue between the students and instructor may be time-consuming, but the instructors must be aware of the work the students are carrying out, making sure that the students know, before initiating each step, how they are going to do it, why, and what to expect. At the beginning of the course, pharmaceuticals are assigned to the students, who do a time-constrained bibliographic search in Chemical Abstracts (CA), either in printed form or through the SciFinder database, seeking information on syntheses for the assigned drug. This search (typically 1950 through 1980) frequently renders several nonrecoverable papers or patents, so it is sometimes necessary to discuss alternatives, and then plan the project and design experimental work based on nondetailed procedures outlined in CA, turning the process into authentic laboratory research. Laboratory limitations (time, materials, and equipment) are taken into account in choosing a synthetic strategy, as well as in designing each experiment; nonetheless, additional support from a research laboratory is sometimes necessary for reagents and facilities, which facilitates the teachingÀ research link. Students learn that, even for the reproduction of methodology from a formal paper, adaptations or modifica- tions may be necessary, so they are encouraged to initially explore ABSTRACT: This article describes one of the projects in the advanced undergraduate organic chemistry laboratory course concerning the synthesis of two local anesthetic drugs, prilocaine and benzocaine, with a common three-step sequence starting from toluene. Students undertake, in a several-week independent project, the multistep synthesis of a pharmaceutical drug, comprising instructor-guided tasks such as literature search, planning, critical discussion, experimental design, observation, and results interpretation. In this project, in addition to searching and using information found in primary and secondary sources, students learn to design the methodology for several of the steps in the reaction sequence, bearing in mind safety and environmental concerns. KEYWORDS: Upper-Division Undergraduate, Laboratory Instruction, Organic Chemistry, Hands-On Learning/Manipulatives, Problem Solving/Decision Making, Amines/Ammonium Compounds, Chromatography, Drugs/Pharmaceuticals, NMR Spec- troscopy, Synthesis