Expected yield: 80% 1.322gExpected yield: 55% 1.122 gExpected yield: 30% 0.5gHonors Cup Synthetic Proposal Section: 220-2 Group Members: Justin Lomont, Koichi Murai, Lara Czabaniuk, Peter Horning Title: Three Step Synthesis of 11-cycloheptylundecanoic acid Introduction: Recently, a fatty acid mixture was isolated from the lipids of the thermoacidophile Alicyclobacillus cycloheptanicus. Subsequently, it was identified as a mixture of ω-cycloheptyl fatty acids which are unique in this organism. It has been suggested that these acids enable the organism to grow in acidic, hot media by providing a more dense cell membrane. This has led to the important understanding of their biosynthetic relations. However, owing to their very low natural abundance, it is necessary to synthesize these fatty acids in order to obtain them in sufficient amount both for their structural establishment and investigation of the involved biosynthetic pathway. One such compound of this class is 11-cycloheptylundecanoic acid. (Reference 1) 11-cycloheptylundecanoic acid is a fascinating biological molecule. Its protective capabilities become more relevant in light of all the environmental concern over acid rain. Alicyclobacillus cycloheptanicus is a type of bacteria and due to its simple nature and quick reproduction, much research can be done on the acids in its membrane. In addition to its biological significance, this synthesis correlates with the material studied in organic chemistry. The first step is an oxidation of a ketone to an alcohol, a process studied in Chemistry 215. Cyclic compounds were studied in Chemistry 210, as were substitutions. Syntheses involving concepts studied in lecture will reinforce and solidify the concepts. Overall synthetic reaction scheme: OOHBrOHONaS2O4DMF, H2O, NaHCO3Ph3PBr2PyridineMg, THF, Li2CuCl4Br(CH2)10CO2MeStep 1 OOHNaS2O4DMF, H2O, NaHCO3 Experimental 1 A solution of substrate (50 mmol) in dioxane (175 mL) or DMF for more difficultly reducible substrates is added to water (175 mL) containing NaHC03 (27.5 9). (When DMF was used as cosolvent, in some cases it was necessary to add some more water during the reduction to prevent gel formation.) When no cosolvent is used, the substrate is added neat. Sodium dithionite (12.5 g) is added and the reaction mixture refluxed for 4 h during which time three additional 12.5-g portions of Na2S204 are added. (A total of three 12.5-g portions of Na2S204 sufficed for the reductions of benzaldehyde, furfuraldehyde, 4-tert-b~-tylcyclohexanone, adamantanone, and norbornanone.) The reaction is carried out under an atmosphere of nitrogen. After the mixture cooled to room temperature, water is added until the solution becomes clear and thereafter the solution is extracted with ether (furfuryl alcohol and y-valerolactone were isolated by continuous extraction with ether for 7 and 72 h, respectively). When DMF is used as cosolvent the ether extracts are backwashed twice with water to remove traces of DMF. After the solution is dried (MgS04) and the ether is removed, the products are isolated by either distillation or recrystallization. Identification is based on melting or boiling points, infrared and 'H NMR spectra, and comparison with authentic materials. All reductions were carried out on a 2-mmol scale and for purposes of isolation were also done on a 50-mmol scale. The reaction is also done in nitrogen at a temperature of 85 degrees Celsius. Table I estimates 97% yield of cycloheptanol when reaction done in DMF. (48.5 mmol) (From Reference #2) Deviations from referenced experimental for 216: We will be using DMF as the solvent as it produces a higher yield and is more readily available. A four hour reflux is not feasible given the time we spend in lab. We propose a two and one half hour to three hour reflux in order to fit within the time constraints of 216. Due to the decreased reflux time and any experimental error, we estimate the yield to be 80% instead of 97%. The estimated yield is 48.5 mmol, which is 5.472 g. We need 1.316g for step two of the synthesis, so the materials used in this step need to be scaled down. After taking the new estimated yield into account, we found that scaling reagents and solvents down by a factor of 3.45 would produce an adequate amount of product. The new masses and volumes of reagents and solvents are as follows: 14.5 mmol of cycloheptanone (1.624 g) in 50.73 mL DMF and 50.73 mL water with 7.971 g NaHCO3 dissolved in it 3.623 g Na2S2O4 added to the mixture four separate times. The times given for extraction are not feasible given the time constraints of Chem 216.We suggest extraction with ether 3 times and then recrystallization or distillation for further isolation. The possible impurity of the product was also taken into account when the new yield was estimated. Expected yield: 80% 1.322g Safety, disposal and green issues 1: Though this experimental uses a large amount of Na2S2O4, the material is much safer to use than metal hydrides to reduce ketones. It will not explode. Using water as a solvent enables us to reduce use of toxic solvents. The experiment will of course need t o be done under a fume hood, especially since sodium dithionite will emit a toxic gas if it comes into contact with an acid. Sodium dithionite is sensitive to the air, and we must perform the transformation in nitrogen. DMF is a skin irritant and direct contact with it should be avoided. (From MSDS) Step 2 OHBrPh3PBr2Pyridine Experimental 2 To a cooled ( 0C) and stirred solution of triphenylphosphine ( 7.86 g, 0.03 mol) in CH2Cl2 (50 mL) was added Br2 (1.6 mL) in CH2Cl2 (50 mL) dropwise over a period of 30 min. To the resulting white suspension was added a solution of cycloheptanol (3.42 g, 0.03 mol) in pyridine (2.6 mL) over a period of 1 h while cooling was maintained externally. After stirring the mixture for 3 h, the solvent was removed under reduced pressure. The residue was chromatographed on a silica gel column, eluting with petroleum ether. The evaporation of the solvent furnished Cycloheptyl bromide (3.7 g, 69.8%): b.p. 82C/10 mm; IR: 2928, 1458 cm-1; 1H-NMR: δ 1.5 (m,12H, 6 x CH2), 3.4 (m, 1H, CHBr). (From reference #1) Deviations from referenced experimental for 216: The 3 hour stirring time is very hard to accomplish within one lab period. We propose stirring the mixture for two hours in order to complete the synthetic step within one four-hour lab
View Full Document
Unlocking...