1. Exploration of the Synthesis of Silatranes and the Contest for Nitrogen’s Lone Pair
Kassie Picard, Arthur Greenberg, Holly Guevara
Department of Chemistry, University of New Hampshire, Durham, NH
Spring 2017
Silatranes are bicyclic molecules with silicon coordinated to the nitrogen. This weak bond between nitrogen and silicon is formed by delocalization of the nitrogen lone pair. The typical N—Si bond is 2.45 Å, like in compound 1. These molecules have important biological functions in hair-growth, wound healing, and antibacterial effects. This project aimed to explore the N—Si bond length when there is a carbonyl group adjacent to nitrogen, competing with silicon for the lone pair. The goal of this product was to produce compound 2, 1-methyl-4-silatranone, via a simple four-step reaction with a “pseudosilatrane” intermediate. The final step in the synthesis was closing the third bridging ring making the amide linkage (scheme 2).1
Figure 1. Dative bond between nitrogen and silicon in a silatrane and in the proposed silatranone.
The first part of this project focused on the synthesis of the “pseudosilatrane” (3), using diethanolamine and methyltriethoxysilane (Scheme 1).2 Different reaction conditions were explored to drive the production of product 3, including adding a protecting group to diethanolamine (Scheme 1B). Each product was analyzed by 1H NMR to determine the abundance and purity of the product.
The synthesis of the pseudosilatrane is still in progress. All 1H NMR data acquired were overwhelmingly populated with solvent and reactant peaks. The unknown peaks in the NMR spectra are likely byproduct that polymerized during the reaction.
Introduction
The original goal for this project was to produce the pseudosilatrane, 3, which could then be closed into the final product, 1-methyl-4-silatanone, 2, that contained a carbonyl group adjacent to the nitrogen (scheme 2). Future work for this project would include continuing to modify reaction conditions to produce 3, then add the correct substituents to produce the product, 1-methyl-4-silatanone.
Scheme 2. Proposed route for the synthesis of 1-methyl-4-silatranone.
The synthesis of the pseudosilatrane, 3, is in progress. Neat and dilute reaction conditions were not enough to drive the production of the pseudosilatrane. The effects of adding a protecting group to diethanolamine are still being explored.
Thank you to the UNH Department of Chemistry for their efforts and support during this research project.
Morgan, J., Guevara, H., Ritzgerald, R., Dunlap-Smith, A., Greenberg, A. Ab initio computational study of 1-methyl-4-silatranone and attempts at its conventional synthesis Structural Chemistry
Piekos, R., Sujecki, R., Sankowski, M. Z. anog. Allg. Chem ,
Puri, J., Raghubir, S., Cahal, V. Silatranes: a review of synthesis, structure, reactivity, and applications. Chem. Soc. Rev., ,
Sliter, B., Morgan, J., Greenberg, A. 1-Azabicyclo[3.3.1]nonan-2-one: nitrogen versus oxygen protonation. Journal of Organic Chemistry ,
Table 1. Modified reaction conditions for the synthesis of the “pseudosilatrane”.
Future Work
Moles
Methyltriethoxysilane
Moles Diethanolamine
(scheme 1A)
Conditions
5.6 mmol
5.7 mmol
Neat, C
3.05 mmol
Basic Conditions, dilute in toluene, C
2.39 mmol
2.83 mmol
Dilute in DCM (500 mL), C
Methyltrimethoxysilane
Moles Boc-protected Diethanolamine
(scheme 1B)
2.36 mmol
1.72 mmol
Dilute in DCM (500 mL), C
Results and Discussion 2
50-600C 4 3 5
50-600C
neat
KOH
dilute A A B B 1 2
Experimental Design B
Conclusions
toluene
Chloroform B B B
toluene B
Unknown A A
Acknowledgements
Figure 2. 1H-NMR for the reaction of diethanolamine and methyltriethoxysilane neat at C (in CDCl3).
Figure 3. 1H-NMR for the reaction of diethanolamine with potassium hydroxide and methyltriethoxysilane in toluene with a 2.5 hour reflux at C (in CDCl3).
30-350C
40-500C
References
dilute
dilute E C D A B
A.) B
toluene 3 B E B
Methanol
B.) A E A E E
Scheme 1. Proposed routes for the synthesis of the “pseudosilatrane”.
Figure 5. 1H-NMR for the reaction of boc protected diethanolamine and methyltrimethoxysilane in DCM with a 2.5 hour reflux at C (in CDCl3).
Figure 4. 1H-NMR for the reaction of diethanolamine and methyltriethoxysilane in DCM with a 2.5 hour reflux at C (in CDCl3).