1. Application of Correlation-Gas Chromatography to Problems 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 October 3, 2011

2. Outline The Correlation-Gas Chromatographic Method Applications 1) Evaluation of the vaporization enthalpies of large molecules, the n-alkanes, C 21 to C 92. 2) Evaluation of the vaporization enthalpies of tautomeric mixtures. 3) Identifying unusual interactions in heterocyclic systems 4) Measurement of Vapor Pressure Isotope Effects

3. 1.The Correlation-Gas Chromatographic Method A typical series of isothermal gas chromatograms as a function of temperature; the compounds in these chromatograms are hydrocarbons

4. Fundamentals of Correlation –Gas Chromatography t nrr : time of a non-retained reference; a measure of the time needed to travel through the column; usually the solvent or methane t a : adjusted retention time: t analyte – t nrr ; a measure of the time the analyte spends on the column; t a is inversely proportional to the vapor pressure of the analyte off the column A plot of ln(t o /t a ) versus 1/T (K -1 ) results in a linear relationship with a slope equal to the enthalpy of transfer from the column to the gas phase, -  g sln H m (T m )/R; t o = 1 min  g sln H m (T m ) =  l g H m (T m ) +  sln H m (T m ) Enthalpies of transfer values measured at T m are found empirically to correlate linearly with the vaporization enthalpies of standards evaluated at any temperature, including T= 298.15 K Since solids do not crystallize on the column, the measurement provides the vaporization enthalpy of the solid Peacock, L. A.; Fuchs, R Enthalpy of Vaporization Measurements by Gas Chromatography, J. Am. Chem. Soc. 1977, 99, 5524-5. Lipkind, D.; Chickos, J. An Examination of the Factors Influencing the Thermodynamics of Correlation Gas Chromatography as Applied to Large Molecules and Chiral Separations, J. Chem. Eng. Data 2010, 55, 698-707.

5. Experimental retention times for n-C 14 to C 20 : A: Determination of Vaporization Enthalpy

6. Enthalpy of Transfer Determination for Hexadecane ln(t o /t a ) = -  g sln H m (T m )/R*1/T + intercept  g sln H m (T m ) * 8.314 J mol -1 = 60.308 kJ mol -1

7. Equations for the temperature dependence of ln(t o /t a ) for C 14 to C 20 where t o = 1 min: ln(t o /t a ) = -  g sln H m (T m )/R*1/T + intercept

8. Vaporization enthalpies (in kJ mol -1 ) of the n- alkanes (C 14 to C 20 ):  l g H m (298.15 K) = (1.424  0.019)  sln g H m (T m ) – (3.98  0.35); r 2 = 0.9991 82  1.1 ? 81.4unknown

9. Correlations between vaporization enthalpy at T = 298.15 K against the enthalpy of transfer

10. B: Determination of Vapor Pressures literature vapor pressure evaluated using the Cox equation a ln (p/p o ) = (1-T b /T)exp(A o +A 1 T +A 2 T 2 ) a Ruzicka, K.; Majer, V. Simultaneous Treatment of Vapor Pressures and Related Thermal data Between the Triple Point and Normal Boiling Temperatures for n- Alkanes C5-C20. J. Phys. Chem. Ref. Data 1994, 23, 1-39. p o = 101.325 kPa

11. Equations for the temperature dependence of ln(t o /t a ) for C 14 to C 20 : ln(t o /t a ) = -  g sln H m (T m )/R + intercept

12. Vapor pressures of n-alkanes (C 14 to C 20 ) at T = 298.15 K: ln(p/p o ) = (1.27  0.01) ln(t o /t a ) - (1.693  0.048); r 2 = 0.9997 -13.3 ? unknown p o = 101.325 kPa

13. Correlation between ln(1/t a ) calculated by extrapolation to T = 298.15 K versus ln(p/p o ) calculated from the Cox equation for C 14 to C 20 (p o = 101.325 kPa) ln(p/p o ) = (1.27  0.01) ln(t o /t a ) - (1.693  0.048); r 2 = 0.9997

14. Vapor pressure -temperature dependence for hexadecane; line: vapor pressure calculated from the Cox equations for C 14, circles; vapor pressures calculated by correlation treating hexadecane as an unknown and correlating ln(t o /t a ) with ln(p/p o ) for C 14, C 15, C 17 -C 20. normal boiling temperature: 560.2 (expt); 559.9 (calcd)

15. c-GC Vaporization. Enthalpy Liquid Vapor Pressure Sublimation Enthalpy (for cryst. solids) + Fusion Enthalpy Boiling Temperature Compare with (  H vap ) lit Compare with (  H sub ) lit Compare with (BT) lit Compare with (ln p/p 0 ) lit Validation of the results

16. Some Advantages and Limitations of Correlation-Gas Chromatography 1. The method works well on hydrocarbons and hydrocarbon derivatives regardless of the hydrocarbon structure 2. With hydrocarbon derivatives, standards need to be chosen with the same number and type of functional group as the compound(s) to be evaluated unless demonstrated otherwise 3. Measurements can be made on small sample sizes and purity is not generally an issue 4. Correlation of the standards needs to be documented experimentally 5. The correlation equations can be used to obtain vapor pressures as well provided vapor pressures of the standards are available and to estimate boiling temperatures. 6. The results are only as good as the quality of the standard data

17. What if suitable standards for the compounds of interest are not available?

18. Functional Group Contributions to Vaporization Enthalpies Functional Group Group Value b acid -C(=O)OH 38.8iodide-I18.0 alcohol -OH29.4ketone>C=O10.5 aldehyde -CHO12.9nitrile-CN16.7 amide [mono-nitro -NO 2 22.8 subst.] -C(=O)NH-42.5heterocyclic aromatic amine [pri.] -NH 2 14.8nitrogen=N-[12.2] amine [sec.] -NH-8.9sulfide>S13.4 amine [tert.] >N-6.6disulfide-SS-[22.3] bromide -Br 14.4sulfoxide>SO[42.4] chloride -Cl 10.8sulfone-SO 2 -[53.0] ester -C(=O)O- 10.5thiolester-C(=O)S-[16.9] ether >O 5.0thiol-SH13.9  l g H m (298.15 K)/(kJ. mol -1 ) = 4.69. (n-n Q ) + (1.3). n Q + b + (3.0) n = number of non-quaternary carbons; n Q = number of quaternary carbons; values in brackets are tentative assignments Chickos, J. S.; Acree, Jr. W. Liebman, J. F. (Frurip, D.; Irikura, K., Editors) Computational Thermochem., Prediction and Estimation of Molecular Thermodynamics, ACS: Washington DC, 1998, pp 63-93

19. Applications The evaluation of vaporization enthalp[ies of large molecules

20. A partial GC trace of a mixture of Polywax 1000 spiked with n- alkanes C 42, C 50 and C 60 run at T = 648 K C 60 1. Applications of correlation gas chromatography for the evaluation of the vaporization enthalpies of large molecules, the n-alkanes, C 21 to C 92.

21. Applications of correlation gas chromatography for the evaluation of the vaporization enthalpies of large molecules, the n-alkanes, C 21 to C 92. Reliable vaporization enthalpies and vapor pressures are available up to eicosane Using the available data from heptadecane to eicosane, vaporization enthalpies were evaluated for C 21,C 22, C 23. These values in turn were used to evaluate the larger n-alkanes in a stepwise process up to C 38, most of which are commercially available. Additionally, a few other larger n-alkanes, C 40, C 42, C 48, C 50, and C 60 are likewise commercially available. These were used in conjunction with polywax to evaluate vaporization enthalpies and vapor pressures up to C 92 (even series) Since very little experimental data was available for comparison, the results from correlation gas chromatography were compared with estimations by PERT2 a and estimated Antoine Constants b a PERT2 is a FORTRAN program written by D.L. Morgan in 1996 which includes parameters for n-alkanes from C 1 to C 100 and heat of vaporization and vapor pressure correlations. Morgan, D. L.; Kobayashi, R. “Extension of Pitzer CSP models for vapor pressures and heats of vaporization to long chain hydrocarbons,” Fluid Phase Equilibrium 1994, 94, 51-87. b Kudchadker, A. P.; Zwolinski, B. J. “Vapor Pressures and Boiling Points of Normal Alkanes, C 21 to C 100,” J. Chem. Eng. Data 1966, 11, 253-55.

22. The vaporization enthalpies at T = 298.15 for C 5 to C 92. N represents the number of carbon atoms. The solid line was derived using the recommended vaporization enthalpies of C 5 to C 20 The empty circles are values calculated values using the program PERT2 The solid circles are values evaluated from correlations of  sln g H m (T m ) with  l g H m (298.15K). Vapor pressures and Vaporization Enthalpies of the n Alkanes from C78 to C92 at T = 298.15 K by Correlation–Gas Chromatography, Chickos, J. S.; Lipkind, D. J. Chem.Eng. Data 2008, 53, 2432–2440. curvature

23. N  l g H m (298.15 K) kJ mol -1 N  l g H m (298.15 K) kJ mol -1 N  l g H m (298.15 K) kJ mol -1 N  l g H m (298.15 K) kJ mol -1 526.4221106.8±2.636182.8±5.564315.4±2.9 631.5222111.9±2.737187.5±5.666324.0±3.0 736.5723117.0±2.838192.5±5.7 b 68331.9±3.0 841.5624121.9±2.840203.5±2.970340.3±3.1 946.5525126.8±2.942213.5±2.172348.4±3.2 1051.4226131.7±3.344223.7±2.374356.2±3.3 1156.5827135.6±3.346233.3±2.376364.3±3.3 1261.5228141.9±5.148243.0±2.478372.1±1.4 1366.6829147.1±5.350252.5±2.580379.6±2.2 1471.7330152.3±5.352261.8±3.682387.2±2.4 1576.7731157.2±1.4 b 54271.0±3.784394.0±3.2 1681.3532162.5±1.456279.7±3.886402.2±2.6 1786.4733167.6±1.458288.5±3.988409.3±3.9 1891.4434172.7±1.560299.9±3.090416.5±4.3 1996.4435178.1±5.4 b 62306.8±2.892424.5±4.5 The Vaporization Enthalpies of the n-Alkanes at T = 298.15 K As A Function of the Number of Carbon Atoms, N How is it possible to measure a vaporization enthalpy greater that a C-C bond strength (~335 kJmol -1 )?

24. Values of at Δ sln g H m (449 K) and Δ l g H m (449 K) on an SPB-5 Column T m = 449 K -slope/T intercept Δ sln g H m (449 K) Δ l g H m (449 K) kJ  mol -1 kJ  mol -1 lit 1 calcd (eq 1) tetradecane 6393.8±95 14.161±0.01 53.2±0.8 56.92 57.0±0.8 pentadecane 6787.9±73 14.597±0.01 56.4±0.6 60.71 60.6±0.8 hexadecane 7251.5±62 15.190±0.01 60.3±0.5 64.50 64.8±0.9 heptadecane 7612.6±65 15.587±0.01 63.3±0.5 68.19 68.1±0.9 octadecane 8014.8±71 16.070±0.01 66.6±0.6 72.11 71.8±1.0 nonadecane 8457.4±74 16.640±0.01 70.3±0.6 76.01 75.8±1.0 eicosane 8919.6±85 17.257±0.01 74.2±0.7 79.81 80.1±1.1  g l H m (449 K)/kJ  mol -1 = (1.098  0.0133)  sln g H m (449 K) - (1.39  0.25) r 2 = 0.9993 (1) 1 Ruzicka, K.; Majer, V. Simultaneous Treatment of Vapor Pressures and Related Thermal data Between the Triple Point and Normal Boiling Temperatures for n-Alkanes C 5 -C 20. J. Phys. Chem. Ref. Data 1994, 23, 1-39. Vapor pressures and vaporization enthalpies for C 14 to C 20 are known over a large temperature range.  g l H m (T m ) and Δ sln g H m (T m ) correlate at any temperature  sln g H m (T m ) =  l g H m (T m ) +  sln H m (T m )  sln H m (T m ) must be of opposite sign to  l g H m (T m )

25.  l g H m (509 K)/kJ  mol -1 = (1.062  0.004)  sln g H m (509 K) + (8.94.02  0.07) r 2 = 0.9999 Values of at Δ sln g H m (509K) and Δ l g H m (509 K) on an SPB-5 Column -slope T intercept Δ sln g H m (509 K) Δ l g H m (509 K) kJ ⋅ mol -1 kJ ⋅ mol -1 lit 1,2 calcd heptadecane 6108.2±78.2 12.148±0.00850.8±0.7 62.83 1 62.9±0.3 octadecane6489.9±63.8 12.584±0.00654.0±0.5 66.34 1 66.2±0.3 nonadecane6901.0±58.7 13.077±0.00657.4±0.5 69.74 1 69.8±0.3 eicosane 7270.0±60.5 13.496±0.00660.4±0.5 73.07 1 73.1±0.3 heneicosane7670.9±65.3 13.974±0.00663.8±0.5 76.66 2 76.6±0.3 docosane 8064.5±71.6 14.439±0.00767.1±0.6 80.13 2 80.1±0.4 tricosane8451.1±73.9 14.897±0.00870.3±0.7 83.54 2 83.5±0.4 1 Ruzicka, K.; Majer, V. Simultaneous Treatment of Vapor Pressures and Related Thermal data Between the Triple Point and Normal Boiling Temperatures for n-Alkanes C 5 -C 20. J. Phys. Chem. Ref. Data 1994, 23, 1- 39. 2 Chickos, J. S.; Hanshaw, W. Vapor pressures and vaporization enthalpies of the n-alkanes from C 21 -C 30 at T = 298.15 K by correlation–gas chromatography, J. Chem. Eng Data 2004, 49, 77-85.

26. -Δ sln g H m (449 K) -Δ l g H m (449 K) (lit) Δ sln H m (449 K) kJ ⋅ mol -1 tetradecane -53.2±0.8 -56.92 3.7±0.8 pentadecane -56.4±0.6 -60.71 4.3±0.6 hexadecane -60.3±0.5 -64.5 4.2±0.5 heptadecane -63.3±0.5 -68.19 4.9±0.5 octadecane -66.6±0.6 -72.11 5.5±0.6 nonadecane -70.3±0.6 -76.01 5.7±0.6 eicosane -74.2±0.7 -79.81 5.6±0.7 -Δ sln g H m (509 K) -Δ l g H m (509 K) (lit) Δ sln H m (509 K) kJ ⋅ mol-1 heptadecane -50.8±0.7 -62.83 12.0±0.7 octadecane -54.0±0.5 -66.34 12.3±0.5 nonadecane -57.4±0.5 -69.82 12.4±0.5 eicosane -60.4±0.5 -73.07 12.7±0.5 heneicosane -63.8±0.5 -76.66 12.9±0.5 docosane -67.1±0.6 -80.13 13.0±0.6 tricosane -70.3±0.7 -83.54 13.2±0.7  g sln H m (T m ) =  l g H m (T m ) +  sln H m (T m ) Enthalpies of Condensation: -  sln g H m (T), -  l g H m (T) and  sln H m (T) as a Function of Temperature

27. Figure. The effect of temperature, 450, 509, 539 K, on the magnitude of  sln H m (T/ K). ■, eicosane; ●, nonadecane.

28. Conclusions: 1.The enthalpy of interaction of analyte with the column is endothermic and a function of temperature; this allows access to the measurement of large vaporization enthalpies 2.This may also help focus GC peaks and oppose diffusion broadening 3.The overall enthalpy of condensation on the column is still highly exothermic, just less so then might have been imagined

29. 2. An Application of Correlation-Gas Chromatography to a Tautomeric Mixture 0.186 0.814 The enthalpy of formation of the equilibrium mixture of the pure liquid, (-425.5±1.0)kJ·mol -1, has been reported by Hacking and Pilcher. Acetylacetone forms a number of metal complexes whose enthalpies of formation have been used to determine metal oxygen bond strengths. Hacking, J.M.; Pilcher, G. J. Chem. Thermodyn. 1979, 11, 1015-1017. Irving, R.J.; Wadso, I. Acta Chem.Scand. 1970, 24, 589-592

30. Table. Summary of all enthalpy differences between 2,4-pentanedione and (Z)-4-hydroxy-3-penten-2-one in the liquid and gas phase available to Hacking and Pilcher, and Irving and Wadso. Enthalpy differences measured by the temperature dependence of the equilibrium constant.  H diketo/enol (T m )liq kJ mol –1 T m/ K  H diketo/enol (T m )gas kJ mol –1 T m /KMethodYear –18.0388UV1977 –7.5±1.5373Photoelectron Spectroscopy 1974 –11.9±0.8306 NMR1966 –16.3 1959 –11.3±0.4 NMR1957 –7.8273Bromination1952 –10.0±0.8386IR1951

31. C 5 H 8 O 2 (gas, 93.3%enol) C 5 H 8 O 2 (liquid, 81.4%enol) C 5 H 8 O 2 (gas, 100%enol) C 5 H 8 O 2 (liquid, 100%enol) ∆H k/e = +0.67 kJ mol -1 ∆H k/e = -2.1 kJ mol -1 ∆ l g H m (298.15K) = (41.8 ± 0.2) kJmol -1 measured calorimetrically ∆ l g H m (298.15K) = (43.2 ± 0.2) kJ mol -1 A trace of concentrated sulfuric acid was used by Irving and Wadso to rapidly equilibrate the diketo and enol forms. Since the enol is more volatile, it was assumed that tautomerization of the diketo form to the enol contributed – 2.1 kJ mol -1 during vaporization.. It was also assumed that the composition in the gas phase was the equilibrium concentration. ∆ l g H m (298.15K) = (41.8 ± 0.2) – ( -2.1 - 0.67) = (43.2 ± 0.2) kJmol -1 Vaporization Enthalpy of the Pure Enol at T = 298.15 K

32. The thermochemical scheme to calculate the enthalpy of formation of (Z)-4-hydroxy-3- pentene-2-one and 2,4-pentanedione scheme used by Hacking and Pilcher in 1979 gas, 100% diketo (–374.4  1.3) gas,100% enol (–384.4  1.3) liquid,100% diketo (–416.3  1.1) (–427.6  1.1) liquid,100% enol  f H m (298.15 K) / kJ mol –1 x(enol) liquid, 81.4% enol 18.6% diketo (-425.5  1.0)  diketo/enol H m (g)=( – 10.0  0.8)  diketo/enol H m (l)=( – 11.3  0.4)  l g H m (298.15K) = (43.2  0.2) 0 1 0.814

33. The enthalpy difference of the two tautomers in the gas phase was measured by infrared spectroscopy in 1951 Gas Phase FT-IR spectrum of 2,4-pentanedione, Aldrich Chemical Co.

34. The enthalpy difference of the two tautomers in the gas phase was re- measured by gas phase 1 H NMR spectroscopy in 1985. 5.3 ppm enol vinyl 1 H 3.3 ppm keto methylene 1 H 1.9 ppm enol methyl 1 H 2.0 ppm keto methyl 1 H Folkendt, M.M.J.et.al. Phys. Chem. 1985, 89, 3347-3352

35. Table. A summary of all the enthalpy differences measured between 2,4-pentanedione and (Z)-4-hydroxy-3-penten-2-one in the liquid and gas phase. Enthalpy differences measured by the temperature dependence of the equilibrium constant.  H diketo/enol (T m )liq kJ mol –1 T m/ K  H diketo/enol (T m )gas kJ mol –1 T m /KMethodYear –11.7303 NMR1996 - –17.0422Photoelectron Spectroscopy 1987 –11.8394.5–19.5409NMR1985 –11.7±1.3311 NMR1982 –18.0388UV1977 –7.5±1.5373Photoelectron Spectroscopy 1974 –11.9±0.8306 NMR1966 –16.3 1959 –11.3 NMR1957 –7.8273Bromination1952 –10.0±0.8386IR1951 The gas phase and condensed phase enthalpies are different, suggesting tautomer interaction

36. If ∆H mix ≠ 0 If the solution heats up when the pure diketo and enol are mixed at their equilibrium concentration, it will take more energy to vaporize the two liquids as a mixture at T= 298.15 K ; If the solution cools down, it will take less heat to vaporize the two liquids as a mixture at T = 298.15 K. Since  H diketo/enol (liq) ≠  H diketo/enol (gas),we decided to measure  l g H m (298.15K) Is ∆H mix = 0 ? If the pure enol form( 0.814 mol) is mixed with the pure keto form (0.186 mol) at the equilibrium concentrations, will ∆H = 0 ?

37. Correlation Gas Chromatography: an ideal method for determining the vaporization enthalpy of a pure material even though the material of interest may be present in the mixture provided all components can be separated Gas Chromatograph of acetylacetone

38. Table. Enthalpy of transfer and vaporization enthalpy obtained for (Z)-4-hydroxy-3- penten-2-one. CompoundSlopeIntercept∆ sln g H m (387 K) /kJ mol -1 ∆ l g H m (298.15 K) /kJ mol -1 (lit) ∆ l g H m (298.15 K) /kJ mol -1 (calcd) 3-hydroxybutanone -3358.810.09227.9248.7 (Z)-4-hydroxy-3-penten-2- one -3703.910.52030.7950.8±0.6 ethyl 2-hydroxypropanoate-3942.710.97732.7852.552.3 4-hydroxy-4-methyl-2- pentanone -3998.010.91433.2452.352.6 ethyl 3-hydroxybutanoate-4516.711.71237.5555.955.8 ethyl 3-hydroxyhexanoate-5476.813.02045.5361.961.6 o-hydroxyacetophenone-5213.312.05343.3459.660.0  l g H m (298.15 K)/kJ mol –1 = (0.734±0.021)  sln g H m (359 K) + (28.21±0.32) r 2 = 0.997

39. Table. Enthalpy of Transfer and Vaporization Enthalpies obtained for 2,4- pentanedione CompoundSlopeIntercept∆ sln g H m (328 K) /kJ mol -1 ∆ l g H (298.15 K) /kJ mol -1 (lit) ∆ l g H m (298.15K) /kJ mol -1 (calcd) 2,3-butanedione-3153.81.49326.2239.038.9 2,4-pentanedione-4305.812.03435.8051.2±2.2 2,2,4,4-tetramethyl- cyclobutanedione -4603.412.28538.2754.254.3 benzoquinone-4614.412.11138.3653.454.4 2,5-hexanedione-4800.512.59239.9157.556.4  l g H m (298.15 K)/kJ mol –1 = (1.283±0.1)  sln g H m (328 K) + (5.21±1.1) r 2 = 0.989

40. (Z)-4-hydroxy-3-penten-2-one ∆ l g H m (298.15K)/kJ. mol -1 (corr- gas chromatography)=(50.8±0.6) kJ mol -1 ∆ l g H m (298.15K)/kJ mol-1(measured as a mixture) = (43.2  0.2) kJ. mol –1a a Measured as a mixture but calculated for the pure material ∆H mix = (50.8±0.6) - (43.2 ±0.2) = 7.6±0.6 kJ. mol -1 ∆H keto-enol tautomerism observed = ∆H keto-enol tautomerism real +∆H mix ∆H keto-enol tautomerism real = (-11.3)-(+7.6±0.6) = -18.9±0.6 kJ mol -1 Since the vaporization enthalpy at T = 298.15 K is approximately the same for 2,4-pentanedione and (Z)-4-hydroxy-3-penten-2-one, the difference in the gas phase between the two tautomers is also ~ -18.9 kJ mol -1

41. gas, diketo (–358.9±2.5) kJ mol -1 gas, 100% enol (–378.2±1.2) kJ mol -1 liquid, diketo (–410.1±1.2) kJ mol -1 (–429.0±1.0)kJ mol -1 liquid, 100% enol x(enol) Δ l g H m =(51.2±2.2) kJ mol -1 ∆ diketo/enol H m (l)= -18.9 kJ mol -1  l g H m = (50.8±0.6) kJ mol -1 0 1 0.814 ∆ diketo/enol H m (g) = (-19.3±2.8) kJ mol -1 (-19.5)kJ mol -1 Folkendt,M. et al. The enthalpies of formation of the tautomers of acetylacetone in the liquid phase and in the gas phase

42. Table. Summary of Standard Molar Enthalpies at T = 298.15 K of the Two Acetylacetone Tautomers Compound  f Hº m (l) / kJ mol –1  l g H m / kJ mol –1  f Hº m (g) / kJ mol –1 2,4-pentanedione –410.1  1.2 [–416.3  1.1] 51.2  2.2 –358.9  2.5 [–374.4  1.3] Z 4-hydroxy-3- penten-2-one –429.0  1.0 [–427.6  1.1] 50.8  0.6 [43.2  0.1] –378.2  1.2 [–384.4  1.3] ∆ f H m (T = 298.15 K, liquid, 81.4% enol and 18.6% diketo) = -425.5±1.0 kJ mol -1. values in the brackets are the previous accepted values. Temprado, M.; Roux, M. V.; Umnahanant, P.; Zhao, H.; Chickos, J. S. J. Phys. Chem. B. 2005; 109, 12590-12595.

43. Unknowns: s-triazine Pyrimidines Pyridazines Standards: Pyrazines Pyridines 1,2-Diazines Application 3: Identifying unusual interactions in heterocyclic systems

44.  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 = 0.9865) 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

45. 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

46. 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.

47. 58.7  1.4 56.5  2.0 -2.2  2.4 Vap. Enth. Calc, kJ  mol -1 : Vap. Enth. Lit, kJ  mol -1 : Difference, kJ  mol -1 : 59.6  1.4 61.1  1.1 1.5  1.8 67.3  1.6 71  1.9 3.7  2.5 81.9  0.8 89.2  2.3 7.3  2.4 76.7  0.7 78.8  2.2 2.1  2.3 Vap. Enth. Calc, kJ  mol -1 : Vap. Enth. Lit, kJ  mol -1 : Difference, kJ  mol -1 : A summary of the vaporization enthalpies for diazines at T = 298 K 46.4  2.0 53.5  0.4 7.1  2.0 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

48. Vaporization Enthalpies Using Pyridine Derivatives as Standards  l g H m (298 K) (kJ  mol -1 )  l g H m (298 K) (kJ  mol -1 ) [Lit]  l g H m (298 K) (kJ  mol -1 ) 1-MeIMI 48.6  2.2 55.6±1.3 6.8  3.6 1-EtIMI 51.4  2.3 66.0±3.9 14.6  3.7 1-Phpyrazole 63.5  2.0 70.2±3.46.7±3.9 1-BzIMI 72.3  3.8 83.0±1.010.8±3.9 What structural factors influence this behavior ? A Study of the Vaporization Enthalpies of Some 1-Substituted Imidazoles and Pyrazoles by Correlation-Gas Chromatography, Lipkind, D.; Plienrasri, C. Chickos, J. S. J. Phys. Chem. B 2010, 114, 16959–16967 1-EthylIMI

49. Unknowns: Standards Set 1 Standards Set 2

50. /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

51. 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

52. 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.

53. 4) Measurement of Vapor Pressure Isotope Effects

54. A typical gas chromatogram of a series of labeled/unlabeled hydrocarbons run on an RTX-1 column at T = 300 K; in order of elution, heptane-d 16 /heptane, toluene-d 8 /toluene, octane-d 18 /octane, p-xylene-d 10 /p-xylene, o-xylene-d 10 /o-xylene. The small peak with the shortest retention time is methane. Typical GC Plot of Deuterated and Undeuterated Hydrocarbons n-C 7 H 16 ; n-C 7 D 16 CH 3 C 6 H 5 ; CD 3 C 6 D 5 n-C 8 H 18 ; n-C 8 D 18 p-CH 3 C 6 H 4 CH 3 o-CH 3 C 6 H 4 CH 3

55. slope intercept  sln g H m (293 K)  l g H m (298)/kJ. mol -1 kJ. mol -1 lit calc hexane-d 14 -3439.9 10.286 28.60 31.47±1.6 hexane -3472.3 10.308 28.87 31.52 31.74±1.6 cyclohexane-d 12 -3576.4 10.111 29.73 32.61±1.7 cyclohexane -3601.7 10.127 29.94 33.12 32.83±1.7 heptane-d 16 -4018.6 11.215 33.41 36.32±1.9 heptane -4058.5 11.252 33.74 36.57 36.66±1.9 toluene-d 8 -4209.2 11.184 34.99 37.92±2.0 toluene -4215.1 11.169 35.04 37.99 37.97±2.0  l g H m (298.15 K)/kJ. mol -1 =(1.009  0.056)  sln g H m (293 K) + (2.615  0.27), (r 2 = 0.9946) Table. Deuterium Isotope Effects on Vaporization Enthalpy

56. Measurement of Vapor Pressure Isotope Effects A/T 3 BT 2 C/T 1 D T b /K (calc) T b /K (exp) p H /p D 298.15 K hexane-d 14 -17917619 -45199 -2909.62 9.429 339.3 341.9 0.909 heptane-d 16 -5444070 -218518 -2758.60 9.220 368 371.4 0.892 p-xylene-d 10 -71657137 282831 -4622.31 10.628 410.1 411.5 0.945 o-xylene-d 10 -89591864 419760 -5088.30 11.06 415.7 417.6 0.937 toluene-d 8 -42775261 88847 -3696.58 9.806 383.1 383.8 0.926 ln(p/po) = A(T/K) -3 + B(T/K) -2 + C(T/K) -1 + D Zhao, H.; Unhannanant, P.; Hanshaw, W. Chickos, J. S. The Enthalpies of Vaporization and Vapor Pressures of Some Deuterated Hydrocarbons. Liquid Vapor Pressure Isotope Effects J. Chem. Eng. Data 2008, 53, 1545–1556.

57. Graduate Students William Hanshaw Patamaporn Umnahanant Hui Zhao 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

58. From Left to right: Bill Hanshaw, Maria Victoria Roux, Jim Chickos, Patanaporn Unmahanant (T), Richard Heinz, and Hui Zhao

59. From left to right: Rachel Maxwell, her friend, Richard Heinz, Jim Chickos, Dmitry Lipkind, and Darrell Hasty

60. separation between stacks = 3.24 Å

61. Does a 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