approaches of the CambridgeSoft ChemOffice Ultra 01 program. The ChemDraw Ultra and Chem3D Ultra applications of the main program have been used.
Chemistry of Catechol Sulfates II. Minimization Studies. Zoltan G. Hajos * Formerly at Princeton University, Department of Chemistry, Princeton NJ Abstract Due to the successful minimization studies of the proline catalyzed reactions2 and in the area of benzodioxane derivatives3 we thought to investigate the chemistry of catechol sulfates1 using the MM2 and the MOPAC minimization methods. The Hydrogen bonded catechol O-sulfonic acid-2-hydroxy-4,6-bis-sulfonanilide 3 showed lower MM2 and MOPAC energy levels than the cyclic sulfate 2. The N-methyl analog cyclic sulfate 4 opened with aniline to the catechol-4,6-bis-N-methyl-sulfonanilide 5 showing lower MM2 energy levels than 4. The N-methyl intermediate 4A the analog of the N-H derivative 3 could not be isolated due to the lack of hydrogen bonding. Its MM2 and MOPAC minimization energies were higher than those of the isolated N-H derivative 3. The MM2 and MOPAC minimizations were in good agreement with the earlier described chemistry.1
Keywords: MM2 minimizations, MOPAC minimizations, benzenesulfonanilides, catechol sulfate derivatives, intramolecular H-bonding.
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In an essay entitled “Chemistry of Catechol Sulfates. Regioselective Ring Opening and Stabilization of Reaction Product by Hydrogen Bonding“ the chemistry of cyclic catechol sulfates has been investigated.1. In the essay the regioselective hydrolysis of the cyclic sulfate ring of the sulfonanilide 2 in refluxing aqueous acetone with aniline to the catechol O-sulfonic acid 3 has been described. Compound 3 was stabilized by intramolecular H-bonding. On the other hand, the cyclic sulfate of the N-methyl sulfonanilide 4 remained unchanged in refluxing aqueous acetone with N-methyl aniline. It underwent, however, hydrolysis to intermediate 4A, the N-methyl analog of compound 3 by refluxing it in aqueous acetone in the presence of aniline. Intermediate 4a is not stabilized by intramolecular H-bonding; therefore, it undergoes hydrolysis to the catechol derivative 5 (Schemes 1 and 2 are shown at the end of this paper).
Due to the successful application of the MM2 and MOPAC minimizations in other areas of chemistry2, 3 it was thought to expand the earlier studies and investigate the catechol cyclic sulfate chemistry using similar MOPAC 4 - 6 and MM2 minimization7 approaches of the CambridgeSoft ChemOffice Ultra 01 program. The ChemDraw Ultra and Chem3D Ultra applications of the main program have been used. Chem3D Ultra allowed the use of the CSMopac menu. Using the MOPAC the heat of formation of the appropriate molecule has been determined. In addition CambridgeSoft Corporation’s Chem3D MM2 energy minimization program based on Allinger’s Molecular Mechanics force field version has been used. Figures 1 – 10 show the results of the MM2 and of the MOPAC minimizations of the different compounds and intermediate 4A, respectively.
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Figure 1. Compound 3 MM2 minimized.
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Figure 2. Compound 3 MOPAC minimized.
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Figure 3. Intermediate 4A MM2 minimized.
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Figure 4. Intermediate 4A MOPAC minimized.
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Figure 5. Compound 5 MM2 minimized.
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Figure 6. Compound 5 MOPAC minimized.
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Figure 7. Compound 4 MM2 minimized
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Figure 8. Compound 4 MOPAC minimized.
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Figure 9. Compound 2 MM2 minimized.
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Figure 10. Compound 2 MOPAC minimized.
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DISCUSSION The minimization results have been summarized in Table1. and in the accompanying Datasheet.
Table 1.
0 -50 -100 MM2
-150
MOPAC -200 -250 -300 2
3
4
4A
5
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As expected, the H-bonded product 3 showed lower MM2 and MOPAC energy levels than the cyclic sulfate 2. The N-methyl analog 4 showed higher energy levels than the des-methyl compound 2 due to more steric interactions and no H-bonding. Compound 4 gave the catechol 5 showing lower MM2 energy levels than 4.
The cyclic sulfate group of the N-CH3 derivative 4 does not open with N-methyl aniline. Treatment with aniline, however, opens the cyclic sulfate of compound 4 to intermediate 4A with lower MM2 and MOPAC energy levels. Intermediate 4A could not be isolated most likely because there is no H-bonding to stabilize the open OSO2OH structure of 4A. Its MOPAC was 24,6687 kcal/mole higher than the MOPAC of the NH-derivative 3. Its MM2 was also higher then that of the des-methyl compound 3 (-18.1865 vs. -23,3043). Intermedate 4A therefore collapsed to the catechol 5 whose MM2 energy level is close to that of intermediate 4A. While the MM2 of 5 was lower than that of 4 its MOPAC energy level was higher. This suggests that the steric interactions played a more important role in the conversion of 4 to 5.
It should be emphasized that we first investigated thoroughly the chemistry of the cyclic sulfate derivatives of catechols1 before engaging in the minimization studies of the same. This is in good agreement with the thoughts described by Plata and Singleton8. They summarized their philosophy of scientific interpretation in an excellent paper by stating: “The computations aid in interpreting observations but fail utterly as a replacement for experiment.
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References
1. Chemistry of Catechol Sulfates. Regioselective Ring Opening and Stabilization of Reaction Product by Hydrogen Bonding. ResearchGate · October 2015 DOI: 10.13140/RG.2.1.2108.2329/1
2. Proline Catalyzed Asymmetric Aldol Cyclization: Hajos Parrish Reaction named by Claude Agami. Brief History of the Discovery and Interpretation of the Reaction Mechanism. ResearchGate · August 2015 DOI: 10.13140/RG.2.1.1173.1680 2015-08-18 T 19:45:06 UTC 3. Marginalia to Organic Chemical Synthesis. Interconnectivity of Scientific Approaches (Table 1. and some text added to the original October, 2016 text.) ResearchGate · March 2017 DOI: 10.13140/RG.2.2.13572.73602
4. M. J. S. Dewar and W. Thiel. Ground States of Molecules, 39. MNDO Results for Molecules Containing Hydrogen, Carbon, Nitrogen, and Oxygen. J.Am. Chem. Soc., 1977, 99, 4907-4907.
5. J. J. P. Stewart. MOPAC: A General Molecular Orbital Package. Quant. Chem. Prog. Exch., 1990, 10, 86.
6. H. S. Rzepa, M. Y. Yi, M. M. Karelson, and M. C. Zerner. Geometry Optimization at the Semi empirical Self-Consistent-Reaction-Field Level using the AMPAC and MOPAC programs. J. Chem. Soc. Perkin Trans. II, 1991, 5, 635- 637.
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7. N.L. Allinger, J.Am.Chem.Soc., 1977, 99, 8127-8134. 8. Case Study of the Mechanism of Alcohol-Mediated Morita Baylis−Hillman Reactions. The Importance of Experimental Observations, R. Erik Plata and Daniel A. Singleton J. Am. Chem. Soc. 2015, 137, 3811−3826.
Schemes 1 and 2:
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