Exploration of further Conjugation of 1-(2-Oxo-Oxazolidin-3-yl)butane-1,3-dione via the Synthesis of 1-(2-Oxo-oxazolidin-3-yl)-5-but-4-ene-5-phenyl-1,3-dione

James ChaseDepartment of Chemistry, University of New Hampshire, Durham, NH

December 5th, 2013Introduction

Results:

Future Work:

Acknowledgements:

Under instruction of Dr. Zercher an experiment based upon the work of previous graduate student Ian Taschner was preformed. Ian Taschner’s work involved the synthesis of 1-(2-Oxo-Oxazolidin-3-yl)butane-1,3-dione. This was accomplished by a three step synthesis beginning with the preparation of Meldrum’s Acid from the work up of Malonic Acid with Acetone with an acid, followed by the addition of ethonyl chloride to Meldrum’s Acid. The synthesis was completed via work up with 2-oxazolidone. The goal of the experiment was to test for the capabilities of synthesizing a more conjugated derivative of 1-(2-Oxo-Oxazolidin-3-yl)butane-1,3-dione by altering the acid chloride used in the second step of the synthesis. Meldrum’s acid was reacted with Cinnamoyl Chloride in the second step of the synthesis with the attention of then forming 1-(2-Oxo-oxazolidin-3-yl)-5-but-4-ene-5-phenyl-1,3-dione.

The core of the experiment is in finding possible highly conjugated akyl groups that can be substituted for the R group in the generic 1-(2-Oxo-Oxazolidin-3-yl)butane-1,3-dione.

1McNab, Hamish. "Chemical Society Reviews." Meldrum's Acid - (RSC Publishing). N.p., n.d. Web. 04 Dec. 2013.

2Cantin, Angel. “J. Agric. Food Chem”Isolation of N-(2-Methyl-3-oxodecanoyl)pyrrole and N-(2-Methyl-3-oxodec-8-enoyl)pyrrole, Two New Natural Products from Penicillium brevicompactum, and Synthesis of Analogues with Insecticidal and Fungicidal Activity, 1998, 46, 4748−4753

Procedural Notes: The preparation for Meldrum’s acid used was developed by Dr. McNab at U. of Edinburg at was said to be near quantitative yield1. The addition of cinnamoyl chloride procedure was created based on the addition of ethonyl chloride in Ian Taschner’s thesis and the work done in J. Agric. Food Chem. 1998, 46, 4748−47532. This step had an expected yield of approximate 75%. The final step of the synthesis was planned to be based up the work of Ian Taschner and had an expected yield of 70%.3

Synthesis of Meldrum’s Acid

MP: 90-94C; H1NMR: (100 MHz, Chloroform-d): δ 1.72-174 (s, 3H), 1.72-174 (s, 3H), 3.57-3.59 (s, 1H)

Yield: 1.24 grams

%-Yield: 9.24%

White solid. Crystalline in nature. Broke off in flakes.

The synthesis of Meldrum’s acid was clearly successful in terms of purity. The H1 NMR showed two singlets peaks in range of an alkane effected by an electron withdrawing group such as an ether and another single peak in range of of C-H bond being affected by neighboring Carbonyl groups. Melting Point was very close to the literature melting point of 92-95C. Issues with yield occurred due to a variety of suspected reasons. The major expected reason is that reaction grade acetone was not supplied. The introduction of wet Acetone likely majorly hurt yield.

3Ian Taschner Thesis Work Provided By Dr. Zercher

Preparation of 5-(1-Hydroxybutylid-5-phenyl-1,4-diene-3-one)-2,2-dimethyl-1,3-dioxane-4,6-dione

Yield: .646 grams

% Yield: 30.8%

Orange-pink powder solid

The synthesis was largely successful in formation of mostly pure 5-(1-Hydroxybutylid-5-phenyl-1,4-diene-3-one)-2,2-dimethyl-1,3-dioxane-4,6-dione it’s H1NMR was indicative of 5 phenyl hydrogens, one singlet alkene hydrogen, and an O-H singlet hydrogen. The melting point was very close to the literature melting point of -C. The yield was lower than expected and that is most likely due to use of wet DCM.

Unfortunately the third step of the experiment was not completed so the primary event preformed in the future would be to finish the experiment.

The next step for future work would involve preforming an alternating synthesis using 3,3-dimethylacryol chloride as the acid chloride.

I would like to acknowledge Deepthi Bhoghadi and Sarah Joiner for their role as the mentoring graduate students. Dr. Zercher for providing me with the foundation for my graduate project. And Ian Taschner for his thesis work which was the starting point for my research.

Discussion:

References:

Scheme 2

Scheme 1