1. Adventures in Thermochemistry James S. Chickos * Department of Chemistry and Biochemistry University of Missouri-St. Louis Louis MO 63121 E-mail: jsc@umsl.edujsc@umsl.edu 11 Clydesdales from the Budweiser Brewery St. Louis MO

2. Applications of the The Correlation-Gas Chromatographic Method Objectives: To go where no one else has gone 1. Evaluation of the vaporization enthalpies of large molecules 2. Application of Correlation-Gas Chromatography to a Tautomeric Mixture - Acetylacetone 3.The Vaporization Enthalpies of Drugs and Related Substances 4.Evaluation of the Vaporization Enthalpies and Vapor Pressures of Plasticizers 5.Identifying unusual interactions in heterocyclic systems

3. Diazines and Triazines Structural Chemistry 2009, 20, 49-58

6.  l g H m (298.15 K)/kJ.mol -1 = (0.941  0.07)  sln g H m (358 K) - (13.1  0.59), (r 2 = 0.9765) A Comparison of calculated vaporization enthalpies and normal boiling temperatures with literature values A Examination of the Vaporization Enthalpies and Vapor Pressures of Pyrazine, Pyrimidine, Pyridazine and 1,3,5-Triazine. Lipkind D., Chickos J. S. Structural Chemistry 2009, 20, 49-58 a Literature boiling temperatures from SciFinder Scholar 50.0±0.3 s-triazine

7. Top, from left to right : phthalazine, benzo[c]cinnoline, quinazoline, quinoxaline. Standards: phenazine, 2,6-dimethylquinoline, acridine, 4,7-phenanthroline, 7,8- benzoquinoline, Lipkind, D.; Chickos, J. S. Study of the Anomalous Thermochemical Behavior of 1,2-Diazines by Correlation-Gas Chromatography J. Chem. Eng. Data 2010, 55, 698-707 Unknowns Standards

8. Since all of the compounds studied are crystalline solids, the following equations were used to adjust sublimation and fusion enthalpies to T = 298.15 K and evaluate the vaporization enthalpy Sublimation:  cr g H m (298.15 K)/(kJ·mol -1 )=  cr g H m (T m )+[0.75+0.15Cp(cr)/(J·mol -1 ·K -1 )][T m /K-298.15 K]/1000 Fusion:  cr l H m (298.15 K)/(kJ·mol -1 )=  cr l H m (T fus )+[(0.15Cp(cr)-0.26 Cp(l))/(J·mol -1 ·K -1 )-9.83)][T fus /K-298.15]/1000 Vaporization:  l g H m (298.15 K) =  cr g H m (298.15 K) -  cr l H m (298.15 K) where Cp(cr), Cp(l) refer to the heat capacity of the crystal and liquid, respectively Acree, Jr.; W.; Chickos, J. S. Phase Transition Enthalpy Measurements of Organic and Organometallic Compounds. Sublimation, Vaporization and Fusion Enthalpies From 1880 to 2009, J. Phys. Chem. Ref Data 2010, 39, 1-942.

9. 58.7  1.4 56.5  2.0 -2.2  2.4 503.5/496.2 Vap. Enth. Calc, kJ  mol -1 : Vap. Enth. Lit, kJ  mol -1 : Difference, kJ  mol -1 : Tb/K this work/lit: 59.6  1.4 61.1  1.1 1.5  1.8 511.2/516.2 67.3  1.6 71  1.9 3.7  2.5 440/462 81.9  0.8 89.2  2.3 7.3  2.4 638.3/633 76.7  0.7 78.8  2.2 2.1  2.3 606.9/na Vap. Enth. Calc, kJ  mol -1 : Vap. Enth. Lit, kJ  mol -1 : Difference, kJ  mol -1 : T b /K this work/lit: A summary of the vaporization enthalpies for diazines at T = 298 K 46.4  2.0 53.5  0.4 7.1  2.0 427/481 Difference in the strength of intermolecular interactions between 1,2- diazines and their isomeric counterparts is approximately 6-7 kJ  mol -1 79.7±1.3 78.4±2.0 -1.0  2.4 Lipkind, D.; Chickos, J. S. Study of the Anomalous Thermochemical Behavior of 1,2-Diazines by Correlation-Gas Chromatography J. Chem. Eng. Data 2010, 55, 698-707

10. A good correlation is found between the enthalpy of transfer and the literature values for the 1,2-diazines, Why do the 1,2-diazines behave differently from the 1,3- or 1,4-diazines? Does the stereochemisty or the size of the ring influence the magnitude of the interaction?

11. Rediscovering the Wheel. Thermochemical Analysis of Energetics of the Aromatic Diazines Verevkin, S. P.; Emel’yanenko, V. N.; Notario, R.; Roux, M.V.; Chickos, J.S.; Liebman, J. F. J. Phys. Chem. Lett. 2012, 3, 3454.

14. Unknowns Standards

15. Unknowns: Standards Set 1 Standards Set 2

16. /kJ  mol -1  H Standards Set 1 Transpiration Correlation gas chromatography 2-(N,N-dimethylamino)pyridine (1) 55.2  0.1054.6  2.30.6  2.3 1,5-diazabicyclo[4.3.0]non-5-ene (3) 61.9  0.2161.1  2.40.8  2.4 4-(N,N-dimethylamino)pyridine (2) 68.4  0.9 a 61.3  2.57.1  2.7 1,8-diazabicyclo[5.4.0]undec-7-ene (4) 70.7  0.1567.8  2.62.9  2.6 imidazo[1,2-a]pyridine (6) 67.4  0.260.5  2.66.9  2.6 triazolo[1,5-a]pyrimidine (5)74.2±3.8 b 63.7  2.710.5  4.7 Standards Set 2 imidazo[1,2-a]pyridine (6) 67.4  0.2367.1  4.60.3  4.6 triazolo[1,5-a]pyrimidine (5)74.2±3.8 b 70.7  4.53.5  5.9 4-(N,N-dimethylamino)pyridine (2) 68.4  0.9 a 69.6  3.81.2  3.9 Vaporization Enthalpies as a Function of Standards Used The Vaporization Enthalpies of 2- and 4-(N,N-Dimethylamino)pyridine, 1,5-Diazabicyclo[4.3.0]non-5-ene, 1,8- Diazabicyclo[5.4.0]undec-7-ene, Imidazo[1,2-a]pyridine and 1,2,4-Triazolo[1,5-a]pyrimidine by Correlation –Gas Chromatography, Lipkind, D.; Rath, N.; Chickos, J.S. Pozdeev, V. A.; Verevkin, S. J. Phys. Chem. 2010, 55, 1628-35. All the compounds whose vaporization enthalpy is in red are planar in the solid state; all are reproduced using various pyridazines and imidazole derivatives as standards

17. Table A (kJ  mol -1 ) Lit CGC Ref a (kJ  mol -1 )  (D) b B benzene C5H5NC5H5Npyridine40.2±0.140.0±2.3 1,250.2±2.32.19 B C5H7NC5H7NN-methylpyrrole40.6±0.840.3±2.53,260.3±2.61.96 B C 5 H 11 NN-methylpyrrolidine34.2±0.736.6±2.43,27-2.4±2.51.1 B C6H7NC6H7N3-methylpyridine44.5±0.244.5±2.01,140 ±2.02.4 B C 7 H 10 N 2 2-N,N-dimethylamino-pyridine55.2±0.154.6±2.3tw0.6±2.31.92 B C8H6N2C8H6N2 quinoxaline56.5±2.058.7±1.92,30-2.2±2.80.51 B C 8 H 11 N2,4,6-trimethylpyridine51.0±1.050.4±2.91,19-0.6±3.02.26 C C9H7NC9H7Nquinoline59.3±0.259.5±1.37,18-0.2±1.32.24 B C9H7NC9H7Nisoquinoline60.3±0.1260.1±1.37,18-0.2±1.32.53 B C 10 H 8 N 2 2-2-bipyridyl 67.0  2.3 63.5±3.2 73.5±3.90.69 B C 10 H 9 N2-methylquinoline62.6±0.162.8±1.37,17-0.2±1.32.07 B C 12 H 10 N 2 trans azobenzene74.7±1.6 74.9  0.7 3,28-0.2±1.70 B C 13 H 9 Nphenanthridine80.14 79.3  5.5 7,290.8±5.52.39 B C 13 H 9 Nacridine78.6378.2±1.3 7,290.4±1.32.29 B Table B C4H4N2C4H4N2 pyridazine 53.5  0.446.5  2.2 1,4 7.0  2.2 4.1 B C4H6N2C4H6N2 N-methylimidazole55.6±0.6 48.8  3.5 3,5,6 6.8  3.6 3.7 d B C4H6N2C4H6N2 N-methylpyrazole48.0±1.341.6±2.9tw e,66.4±3.22.29 B C 7 H 10 N 2 4-N,N-dimethylaminopyridine 68.4  0.961.3  2.5 tw7.1±2.74.33 B C9H8N2C9H8N2 N-phenylpyrazole70.2±3.4 63.5  2.9 3,256.7±4.52.0 B C9H8N2C9H8N2 N-phenylimidazole84.6±3.7 67.7  2.1 3,2516.9±4.33.5 B C 12 H 8 N 2 benzo[c]cinnoline 89.2  2.381.9  1.1 2,28 7.3  2.5 4.1 B 42.8±0.2

18. Summary Polarity seems to play a role Extensive conjugation seems to be an important property All compounds exhibiting enhanced intermolecular interactions are planar The crystal structure of 1,2,4-triazolo[1,5-a]pyrimidine suggests the presence of π- π stacking in the solid state Since most of the compounds exhibiting stronger intermolecular interactions examined so far (pyridazines, imidazoles) seem to correlate with each other, this suggests a common interaction responsible for the enhanced intermolecular interactions observed; the origin of this interaction has yet to be identified.

19. separation between stacks = 3.24 Å

20. Graduate Students Patamaporn Umnahanant Dmitry Lipkind Visiting Graduate Students Manuel Temprado, Instituto de Química Física “Rocasolano”, Madrid 28006, Spain Visiting Faculty and Collaborators Maria Victoria Roux, On leave from the Instituto de Química Física “Rocasolano”, Madrid 28006, Spain Sergey Verevkin, University of Rostock, Rostock Germany

21. Scott Hasty Dmitry lipkind Patamaporn Umnahanant T Chatchawat Plienrasri F Sergey Verevkin

22. Does ring size play a role?  All compounds used as standards were six-membered ring heterocycles.  l g H m (298 K) (kJ  mol -1 )  l g H m (298 K) (kJ  mol -1 ) [Lit] 1-methylpyrrolidine 36.6  2.4 34.2±0.7 1-methylpyrrole 40.3  2.5 40.6±0.8 4-methylpyrimidine 43.8  2.6 44.2 2,5-dimethylpyrazine 47.6  2.7 47.0 2,4,6-trimethylpyridine 51.4  2.8 51.5 quinoline 59.2  3.0 59.31 1-methylindole 61.1  3.1 62.2±1.6