crystal structures of pyrazinamide- p-amino benzoic acid

S1  

Crystal structures of pyrazinamide-p-amino benzoic acid cocrystal and their transamidation reaction product, 4-(pyrazine-2-carboxamido)benzoic acid in molten state

Shridhar H. Thorat, Sanjay kumar Sahu and Rajesh G Gonnade*

Center for Materials Characterization, CSIR-National Chemical Laboratory, Pune - 411008, India.

Correspondence e-mail: rg.gonnade@ncl.res.in

Entry Content Page

1 Figure S1. 1H NMR spectrum of cocrystals 1 in DMSO-d6  S2

2 Figure S2. 1H NMR of 4-(pyrazine-2-carboxamido) benzoic acid (2) in

DMSO-d6 

S3 

3 Figure S3. 1H NMR of 4-(pyrazine-2-carboxamido) benzoic acid (2) in

DMSO-d6 with D2O exchange 

S4 

4 Figure S4. IR spectra S5 

5 Figure S5. DSC profile of cocrystal 1 and carboxamide 2  S6 

6 Figure S6. DSC profile of carboxamide 2 S7

7 Figure S7. Overlay of the PXRD patterns of cocrystal 1 (experimental and

simulated)

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8 Figure S8. Overlay of PXRD patterns of cocrystal 1, carboxamide 2 with,

cocrystal components PZA and pABA.

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9 Figure S9. PXRD patterns of cocrystal 1 prepared by different grinding

methods.

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7 Figure S10. TGA plot of cocrystal 1 S11

Figure S11. TGA plot of carboxamide 2 S12

8 Figure S12. Photomicrographs of the cocrystal (1) grabbed HSM studies. S13

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Figure S1. 1H NMR of pyrazinamide (PZA) and p-amino benzoic acid (pABA) cocrystal (1) recorded at 200 MHz in DMSO-d6.

Thu2av2#134.001.001.1r.esp

10 9 8 7 6 5 4 3 2 1 0

2.12

2.23

2.21

0.95

0.88

1.10

1.07

1.00

9.19

9.18

8.85

8.72

8.71

8.71

8.27

7.87

7.63 7.58 6.

556.

51

5.87

3.34

2.52

2.51

2.50

2.49

-0.0

1

N

N O

NH2

Pyrazinamide (PZA)

O

HO

NH2

p-Amino Benzoic Acid (pABA)

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Figure S2. 1H NMR of 4-(pyrazine-2-carboxamido) benzoic acid (2) recorded at 200 MHz in DMSO-d6.

Thu1av2#133.001.001.1r.esp

16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 -4Chemical Shift (ppm)

2.001.900.930.900.860.930.71

TMS

DMSO

Water

2.10

7.94

7.99

8.05

8.098.

868.

878.

978.

989.33

9.34

11.0

5

12.8

212

.83

12.8

412

.85

NH

O

OHO

N

N

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Figure S3. 1H NMR of 4-(pyrazine-2-carboxamido) benzoic acid (2) recorded at 200 MHz in DMSO-d6 with D2O.

NH

O

OHO

N

N

Mon2av2#049.001.001.1r.esp

11 10 9 8 7 6 5 4 3 2 1 0 -1

4.49

1.10

1.09

1.00

DMSO

Water

9.31

9.30

8.94 8.93

8.83

8.83

8.82

8.01

7.97

7.93

-0.0

1

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IR Analysis

Figure S4. Infrared spectra of the PZA-p-ABA cocrystal (1, blue), their molten product (2, green), pyrazinamide (PZA, black) and p-amino benzoic acid (p-ABA, red).

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DSC analysis

Figure S5. DSC profile of PZA – p-ABA cocrystal 1.

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Figure S6. DSC profile of carboxamide 2.

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PXRD analysis

Figure S7. Overlay of PXRD patterns of cocrystal 1, experimental (black) and simulated from

single crystal diffraction data (red).

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Figure S8. Overlay of PXRD patterns of cocrystal 1 (blue), carboxamide 2 (green), PZA (black),

pABA (red).

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Figure S9. PXRD patterns of cocrystal 1 prepared by dry grinding (blue), liquid assisted

grinding (green) and their comparison with PXRD patterns of cocrystals 1 produced from

solution crystallization (magenta), PZA (black) and pABA (red).

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TGA Study

Figure S10. TGA plot of cocrystal 1 showing slight weight loss around melting attributed to the release of ammonia molecules as the byproduct of transamidation reaction in molten state.

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Figure S11. TGA plot of carboxamide 2.

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HSM Analysis

Figure S12. Photomicrographs of the cocrystal 1 grabbed during heating experiment showing thermal response at different temperatures.