Presentation on theme: "Results and Discussion The first reaction (A) to yield 2 proceeded via a radical mechanism with commercially available vinyltrimethylsilane, 1. After careful."— Presentation transcript:
Results and Discussion The first reaction (A) to yield 2 proceeded via a radical mechanism with commercially available vinyltrimethylsilane, 1. After careful workup and purification, the product was determined via 1 H NMR analysis to be the desired compound with a yield of 83% in the salt form. The formation of 2-trimethylsilyethylsulfonylchloride and the synthesis of its sulfonamide Chelsea Gibbs Department of Chemistry, University of New Hampshire, Durham, NH December 5, 2013 Introduction The Zinc Carbenoid-Mediated Chain Extension reaction was first reported in 1997 by Brogan and Zercher. 1 This mild and efficient synthesis converts β-keto esters to their γ-keto homologues. The reformatsky type intermediate 5 generated during zinc mediated chain extension can be trapped with various electrophiles like imines, aldehydes, ketones, halogens etc. to yield the corresponding tandem chain extended product. 1,2 As mentioned above imines were used as electrophiles in tandem chain extension reactions. In an attempt to increase electrophility and the overall reaction rate/efficiency, a sulfonyl group was reacted to form its imine derivative via addition of ammonia. The SES protecting group was implemented due to its easy removal with reagents such as HF. 2 Scheme 1: Sodium β-trimethylsilylethanesulfonate,2, is formed in A then reacted to yield 2-Trimethylsilylethanesulfonyl Chloride, 3 in B. Finally in C via addition of aqueous Ammonia, the synthesis of 2-trimethylsilylethanesulfonamide, 4, is attempted. The compound 2-trimethylsilylethanesulfonamide (4) is reacted with boron triflouride diethyl etherate and benzaldehyde to form the imine starting material in a future tandem chain extension mannich reaction. 2 Scheme 2 below represents the reaction with the synthesized imine. Compound 2 via reaction B was converted to the sulfonyl chloride, 3. 3 The reaction implemented a Vilsmeier reagent to give the chloride source. 4 The reagents thionyl chloride and DMF (N,N- dimethylformamide) created the Vilsmeier reagent that proceeded to chlorinate the sodium sulfonate 2 to produce 3 as a light brown-yellow oil. 5 The crude oil was purified then concentrated to yield 0.0942g. Figure 1 below shows the formation of the Vilsmeier reagent. 1 H NMR analysis determined this to not be the desired compound. Spectra was inconclusive and showed characteristics of either the sulfonic acid or the sulfonic anhydride. To avoid this in the future, salt 2 should be dried with a drying pistol before reacting and the DMF should be added more slowly while temperature is monitored. Figure 1: Formation of Vilsmeier reagent Figure 2: Mechanism of sulfonamide derivative formation via ammonia Due to the unsuccessful sulfonyl chloride synthesis, the SES substituted sulfonamide was never prepared in reaction C. Aqueous ammonia would be added to a solution of 3 and diethyl ether and stirred for 2 hours. 5 The crude would be purified then evaluated via 1 H NMR to determine composition 4. Figure 2 to the right shows the mechanism of this future reaction. Future Work Once the sulfonamide 4 is synthesized to the Imine, the tandem-chain extension reaction can be started. This activated imine is added to the reaction after 1:1 addition of diethylzinc and diiodomethane have been reacted to form the chain extended material. 6 The imine, containing the trimethylsilane group, is predicted to be more electrophilic due to the protection of the imine group than other substituted imines. 1,2 Leading it to react with diethyl zinc and the given substrate to form the chain extended product faster and more efficiently than other imine derivatives. 1 Scheme 2 represents this process. Scheme 2: Outcome of future Tandem Chain Extension Mannich Reaction Acknowledgements: Thanks to Professor Zercher and Group, especially Deepthi Bhogadhi, for support, assistance and knowledge throughout this research. References: 1 Jacobine, Alexander M., UNH Dissertation for Doctor of Philosophy. 2010.; 2 Drew, Kimberly L., UNH Thesis for Bachelor of Arts in Chemistry, 2012. 3 Nahit Gençer, Dudu Demir, Fatih Sonmez, Mustafa Kucukislamoglu. Bioorganic & Medicinal Chemistry, Vol. 20, Issue 9, 1 May 2012. 4 Weinreb, S.M,; Chase,C.E.;,Wipf,P.; Venkatraman, S. Organic Syntheses, Coll. Vol. 10, p.707 (2004); Vol. 75, p.161 (1998). 5 Sacher, J.R.; Weinreb, S.M. 2-Trimethylsilylethanesulfonyl Chloride (SES-Cl)Org. Synth. 1998, 75, 161. 6 Bosshard, H. H; Mory, R.; Schmid, M.; Zollinger, H. Helv. Chim. Acta 1959, 42, 1653-1658.