Mechanochemical Synthesis of Pyrazine:Dicarboxylic Acid ... · phthalic acid. The patterns were recorded at 25°C temperature and room humidity. The most prominent peaks corresponding

1

Mechanochemical Synthesis of Pyrazine:Dicarboxylic Acid

Cocrystals and the study of their Dissociation by

Quantitative Phase Analysis

Mihails Arhangelskis, Gareth O. Lloyd* and William Jones*

Supplementary Information

Electronic Supplementary Material (ESI) for CrystEngCommThis journal is © The Royal Society of Chemistry 2012

2

Table S1. Theoretical and experimental weight loss determined by TGA of the

pyrazine cocrystals.

Cocrystal Weight loss

(experimental) / %

Weight loss

(theoretical) / %

pyrazine:terephthalic 30.0 32.5

pyrazine:phthalic 31.4 32.5

pyrazine:succinic 40.0 40.4

pyrazine:fumaric 39.6 40.8

Figure S1. Close contact between atoms H10 and O1 (x, 3/2-y, ½+z) in the pyr:pht

crystal structure.


3

Figure S2. Molecular arrangements of the pyr:fum crystal faces. Faces (001) and

(100) display hydrophilic character while faces (011) and (102) are mostly

hydrophobic.

Figure S3. Molecular arrangements of the pyr:succ crystal faces. Faces (101) (10 )

and (002) are hydrophilic.


4

Figure S4. Molecular arrangements of the pyr:ter crystal faces. (001) face is

hydrophilic while (011) and (10 ) faces are mostly hydrophobic.

Figure S5. TGA of pyrazine:terephthalic acid cocrystal

Step -68.9038 % -8.9162 mg

Step -30.0234 % -3.8850 mg

!ma1040TGA ma1040TGA, 12.9400 mg

% 50

°C 50 100 150 200 250 300 350 400 450

ma1040TGA 28.02.2011 16:48:16

SW 8.01 e R TA S Lab: METTLER


5

Figure S6. TGA of pyrazine:phthalic acid cocrystal

Figure S7. TGA of pyrazine:fumaric acid cocrystal

Step -66.5472 % -9.2501 mg

Step -31.3654 % -4.3598 mg

!MA1096TGA MA1096TGA, 13.9000 mg

% 50

°C 50 100 150 200 250 300 350 400 450

ma1096TGA 23.02.2011 14:16:45



6

Figure S8. TGA of pyrazine:succinic acid cocrystal

Figure S9. DSC of pyrazine:terephthalic acid cocrystal

Step

Integral

-59.7749 %

-1444.95 mJ

normalized

-8.0756 mg

-489.81 Jg^-1

Step

Onset

-40.0284 %

361.02 °C

Peak

-5.4078 mg

384.82 °C

!ma1078

Integral

ma1078, 13.5100 mg

-656.79 mJ

%

normalized

50

-222.64 Jg^-1

°C

Onset

50

107.79 °C

100

Peak

150

132.14 °C

200

!&ma1040DSC_open_pan

250

ma1040DSC_open_pan, 2.9500 mg

300

Wg^-1

350

5

400

°C

450

50

ma1078TGA

100

24.02.2011 18:03:08

150

SW 8.01

200

e

250

R

300

TA

350

S

êxo

Lab: METTLER

ma1040DSC_open_pan 02.03.2011 13:55:39



7

Figure S10. DSC of pyrazine:phthalic acid cocrystal

Figure S11. DSC of pyrazine:fumaric acid cocrystal

Integral

Integral

-464.36 mJ

-1794.18 mJ

normalized

normalized

-116.09 Jg^-1

-533.98 Jg^-1

Onset

Onset

233.19 °C

266.27 °C

Peak

Peak

257.30 °C

287.59 °C

Integral

Integral

-1208.98 mJ

-1023.58 mJ

normalized

normalized

-302.24 Jg^-1

-304.64 Jg^-1

Onset

Onset

204.72 °C

112.39 °C

Peak

Peak

207.45 °C

138.29 °C

Integral

!ma1074DSC_open

-290.84 mJ

ma1074DSC_open, 3.3600 mg

normalized

Wg^-1

-72.71 Jg^-1

5

Onset

°C

102.63 °C

50

Peak

100

105.22 °C

150

!&ma1096DSC_open

200

ma1096DSC_open, 4.0000 mg

250

Wg^-1

300

5

êxo

°C

ma1074DSC_open_pan

50

10.03.2011 12:53:44

100

SW 8.01

150

e

200

R

250

TA

300

S

êxo

Lab: METTLER



8

Figure S12. DSC of pyrazine:succinic acid cocrystal

Figure S13. IR spectrum of pyrazine:terephthalic acid cocrystal

Integral -857.15 mJ normalized -325.91 Jg^-1 Onset 205.84 °C Peak 238.63 °C



!&ma1084DSC_open_pan ma1084DSC_open_pan, 2.6300 mg

Wg^-1 10

°C 50 100 150 200 250 300 350

êxo ma1084DSC_open_pan 02.03.2011 14:45:11



9

Figure S14. IR spectrum of pyrazine: phthalic acid cocrystal

Figure S15. IR spectrum of pyrazine:fumaric acid cocrystal


10

Figure S16. IR spectrum of pyrazine:succinic acid cocrystal

Figure S17. PXRD pattern of pyrazine:terephthalic acid cocrystal


11

Figure S18. Rietveld refinement of the pyrazine:terephthalic acid cocrystal. The blue

outline shows the experimentally observed diffracted pattern, the red curve shows the

Rietveld fit and the grey outline marks the difference between the calculated fit and

the experimental pattern. Quantitative phase analysis suggests the presence of 3% of

terephthalic acid form II (refcode TEPTH12) impurity.

Figure S19. PXRD pattern of pyrazine: phthalic acid cocrystal


12

Figure S20. Rietveld refinement of the pyrazine:phthalic acid cocrystal.

Figure S21. PXRD pattern of pyrazine:fumaric acid cocrystal


13

Figure S22. PXRD pattern of pyrazine:succinic acid cocrystal

Figure S23. Example of Rietveld refinement of a PXRD pattern recorded on a sample

of pyrazine:phthalic acid cocrystal recorded during the kinetics measurement.

Refinement of the scale factors of mixture components allows to calculate their

corresponding mass fractions (shown in the top right corner).


14

Figure S24. X-ray powder patterns showing the conversion of pyr:pht cocrystal into

phthalic acid. The patterns were recorded at 25°C temperature and room humidity.

The most prominent peaks corresponding to the cocrystal are at 2θ 14.5°, 19.6°, 25.3°

and 29.9°. The major peaks corresponding to phthalic acid are at 2θ 15.1°, 18.2°,

26.6° and 30.2°.

Figure S25. Arrhenius plot describing the dependence of pyr:pht cocrystal

dissociation rate on temperature

-3.00

-2.00

-1.00

0.00

1.00

2.00

3.00

2.96E-03 3.01E-03 3.06E-03 3.11E-03 3.16E-03 3.21E-03 3.26E-03 3.31E-03 3.36E-03

log

(k)

1/T / K-1


Documents

Mechanochemical Synthesis of Pyrazine:Dicarboxylic Acid ... · phthalic acid. The patterns were recorded at 25°C temperature and room humidity. The most prominent peaks corresponding