2. Variable Temperature and Pressure Techniques for in situ Crystallization Roland Boese contributions from: D. Bläser V.R. Thalladi C. Schauerte M. T. Kirchner Erice, 16. 6. 2004 A. Gehrke

3. Variable Temperature and Pressure Techniques for in situ Crystallization Erice, 16. 6. 2004 Roland Boese financial aid: DFGSFB452ratiopharm

4. In situ - Crystallization What is it? Crystallization on the diffractometer in capillaries

5. In situ - Crystallization Why should we do so? Crystals grown outside cannot be transferred to the diffractometer without damageCrystals grown outside cannot be transferred to the diffractometer without damage Better control on crystallization processBetter control on crystallization process

6. In situ - Crystallization How to do it? Fill capillaryFill capillary Mount itMount it Switch on LT-deviceSwitch on LT-device Grow crystalGrow crystal Check crystal qualityCheck crystal quality Collect dataCollect data Solve structureSolve structure

7. Fill capillary

10. Transfer to Diffractometer Detector X-ray-Source Cooling Observation Laser

11. In situ - Crystallization How to crystallize? Simply cool downSimply cool down And warm up againAnd warm up again Why?

12. T melt T V crystal growth V nucleation metastable region critical size we need to heat! In situ - Crystallization

13. How to crystallize? Simply cool downSimply cool down And warm up againAnd warm up again with fingers

14. In situ - Crystallization How to crystallize? Simply cool downSimply cool down And warm up againAnd warm up again with spatulum

15. In situ - Crystallization How to crystallize? Simply cool downSimply cool down And warm up againAnd warm up again with heated wire (loop)

16. In situ - Crystallization How to crystallize? Simply cool downSimply cool down And warm up againAnd warm up again with heated plate

17. In situ - Crystallization How to crystallize? Simply cool downSimply cool down And warm up againAnd warm up again with IR-radiation

18. In situ - Crystallization How to crystallize? Simply cool downSimply cool down And warm up againAnd warm up again with IR-laser

19. In situ - Crystallization Why with laser? Simply cool downSimply cool down And warm up againAnd warm up again with IR-laser

20. In situ - Crystallization Why with laser? Simply cool downSimply cool down And warm up againAnd warm up again with IR-laser Advantages: growing from bottom to top optical observation no mechanical break of capillary control on heat control on position high temperature gradient

21. CO 2 laser laser diode mirror ZnSe - lens turning mirror LT-device Optical Heating and Crystallization Device O.H.C.D. url: http://www.ohcd- system.com In situ - Crystallization

23. undistorted crystallization zone

24. In situ - Crystallization … and Polymorphism studies Meat to the bones What for?What for? LiquidsLiquids GasesGases SolutionsSolutions Phase transitionsPhase transitions Trapping of chemical reaction productsTrapping of chemical reaction products Co-crystalsCo-crystals ClathratesClathrates

25. n-nonanen-nonane –‘rotator' phase circumvent of disordered phases In situ crystallization

26. 25 20 15 10 5 0 -80 -70-60 -50 -40-30-20 -57.03°C phase transition -54.08°C melting point temperature (°C) heat transfer(mW) DSC heating curve of n-nonane shatter crystallization crystallization from solution ordered phase melt rotator phase

27. no crystal seedsno crystal seeds –temperature shocks –ultrasonic –external seeding –internal seeding for ethylenglykol with phenazine (template effect)for ethylenglykol with phenazine (template effect)problems

28. Crystallization techniques

29. ethylen glykolethylen glykol –glassy state In situ - Crystallization

30. phenazine 1,2-diphenyl- ethylene glycol OH N bridges ethylen glykol o o o o o phenazine    Crystallization techniques

31. crystal structure of ethylen glykol R. Boese, H.-C. Weiss, Acta Crystallogr. 1998, C54, 24.

32. Pyridine N H N H N H N H expected packing pattern realized: D. Mootz and H.-G. Wussow, J. Chem. Phys., 1981, 75, 1517. no linear CH···N Z' = 4 no thermodynamic minimum (calculated, S. Price et al., Cryst Eng. Comm. 2002)

33. DSCs pyridine and perdeutero-pyridine in pentane pyridine perdeutero-pyridine

34. Pyridine

35. Pyridine

36. perdeutero- Pyridine

37. Same form found by S. Parsons for high pressure form, but also for the non-deuterated pyridine!

38. α-Form P2 1 /n, 107.138°, 5.8216, 10.4597, 8.9402Å, V = 520, ρ = 0.908 g/cm³ ß-Form P2 1 /c, 107.209°, 7.2414, 8.1909, 10.8014Å, V = 612, ρ = 0.913 g/cm³ molecular complexes and networks Aceton + Acetylene 1 : 12 : 1 O C-H···O

39. Ethynylbenzene + Pyrazine N N

40. ? N N P-Diethinylbenzene + Pyridin

41. sublimation energies in kJ/mol -45.0 -58.7 N N N N 1x 2x -162.4 -164.6 stabilization by 2.2 kJ/mol N N N -53.3 -75.5 2x 1x -182.1 -169.6 destabilization by 12.5 kJ/mol data by Martin U. Schmidt, Frankfurt (ESP charges, Dreiding2.21, optimized)

42. Option 1 N N NNN N N N Option 2 Acetylene + Pyridin

44. Option 3 Option 4 O OO O O O Acetylene + ….

45. Option 5 OOOO Acetylene + ….

46. Option 6 Acetylene + Acetylene

47. Option 7 ππππππππ Acetylene + Acetylene + π -System

48. in situ Cocrystallization of Gaseous Compounds Acetylene + Aceton Acetylene + Benzene Acetylene + Dimethylpyrazine Acetylene + Water Water + Methane Water + Methane Water + Methane + Propane Water + Methane + Propane Water + Methane + Adamantane Water + Methane + Adamantane Water + Propane Water + Propane Gashydrates Acetylene + Dioxane Acetylene + Pyridin Acetylene + Methanol Acetylene + Dimethylpyridin Acetylene + Di-tert-butylpyridin Acetylene + DMSO

49. molecular complexes and networks DMSO + Acetylene

50. Acetylene + Benzene 8.21 Å

51. Acetylene + Benzene

52. Å 1.097 Å at 201K Å 1.157 Å at 123K compare Å 1.20 Å Di-tert-butylethyne Acetylene + Benzene

53. Acetylene + Methanol Cmcm Cmc2 1

54. Acetylene + Methanol

56. Space group P 2 1 2 1 2 1 a = 4.573, b = 7.327, c = 13.158 Å Space group Cmc2 1 a = 6.417, b = 7.228, c = 4.652 Å

57. gas hydrates below the oceans we have twice as much methane in clathrates than the eqivalent of all known fossile fuel in the world up to 10% of the off-shore conveying costs for natural gas is spent to avoid gas hydrates in the sensitive equilibrium methane/water, natural gas is released by heating the oceans, which is again the most effective geenhouse gas

58. Gashydrates Methane + Water Methane + Water Temperature: below 8 °C Temperature: below 8 °C pressure above 20 bar pressure above 20 bar

59. Evaluation: Single ‚Frame‘

60. Multiple Single Crystals (‚oligocrystalline‘ material)

61. 'oligo'-diffractometrypowder-diffractometry single crystal-diffractometry

62. occurence economical relevance ecological relevance Gashydrates 'burning ice'

63. O-H···O Dodecahedron Methane (without H‘s) Tetrakai- decahedron Methane (with H‘s) Propane Hexakai- decahedron Form I Form II Gashydrates

64. Propane Hexakai- decahedron Form II Gashydrates

65. Gashydrate

66. Gashydrate

67. Gashydrate

68. Gashydrate

69. Gashydrate

70. Gashydrate

71. Gashydrate Acetylen + Wasser