Organic Salts of Pharmaceutical Impurity p-Aminophenol
Abstract
:1. Introduction
2. Results and Discussion
2.1. X-ray Crystallography
2.2. Crystal Structure Analysis
2.2.1. PAP+OX− Salt (2:1)
2.2.2. PAP+TA− Salt (1:1)
2.2.3. PAP+SA− Salt (1:1)
2.2.4. PAP+CSA−·H2O Salt (1:1:1)
2.3. Crystallization Experiments
2.3.1. Crystallization of Paracetamol in the Absence of PAP
2.3.2. Crystallization of Paracetamol in the Absence and Presence of PAP
2.3.3. Crystallization of PA in the Presence of PAP and a Counterion
3. Materials and Methods
3.1. Materials and General Methods
3.2. Synthesis of the PAP Salts
3.3. Impurity Spiking Experiments
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds PA, PAP, PAP+SA−, PAP+OX−, PAP+CSA−·H2O, PAP+TA− are available from the authors. |
Compound | PAP+SA− | PAP+OX− | PAP+CSA−·H2O | PAP+TA− |
---|---|---|---|---|
Formula | C13H13NO4 | C7H8NO3 | C16H25NO7S | C10H14NO7 |
MW, g/mol | 247.25 | 154.14 | 359.43 | 259.21 |
Crystal system | triclinic | monoclinic | monoclinic | monoclinic |
Space group, Z | P, 2 | P 21/n, 4 | C2, 4 | P 21, 2 |
a, Å | 6.798(7) | 6.6471(5) | 42.654(2) | 7.206(6) |
b, Å | 8.596(1) | 17.357(7) | 7.4090(3) | 8.043(7) |
c, Å | 10.256(1) | 6.768(5) | 11.765(5) | 10.53 (7) |
α, ° | 93.756(4) | 90 | 90 | 90 |
β, ° | 99.530(4) | 117.233(5) | 97.2740(1) | 98.361(8) |
γ, ° | 94.663(4) | 90 | 90 | 90 |
V, Å3 | 587.2(6) | 694.2(3) | 3575.7(3) | 603.9(1) |
Dc gcm−3 | 1.398 | 1.475 | 1.335 | 1.426 |
μ, mm−1 | 0.105 | 0.117 | 0.212 | 0.123 |
2θ range, ° | 3.0–26.38 | 3.56–26.36 | 2.79–26.39 | 2.86–26.85 |
T, K | 299 | 282 | 304 | 299 |
Total ref. | 14,425 | 7997 | 23,035 | 9330 |
Unique ref. | 2398 | 1414 | 7278 | 2480 |
Obs. ref., I > 2σ(I) | 2046 | 1042 | 5649 | 2347 |
# Parameters | 178 | 117 | 464 | 191 |
R1 [I > 2σ(I)] | 0.0393 | 0.0450 | 0.0474 | 0.0727 |
wR2 | 0.0967 | 0.1003 | 0.1021 | 0.1601 |
S | 0.9792 | 0.9748 | 0.9847 | 0.9779 |
Acid | Product (Ratio in the Bracket) |
---|---|
Oxalic acid (OX) | PAP+OX− Salt (2:1) |
l-tartaric acid (TA) | PAP+TA− Salt (1:1) |
p-Salicylic acid (SA) | PAP+SA− Salt (1:1) |
(1S)-(+)-10-Camphorsulfonic acid (CSA) | PAP+CSA−·H2O Salt hydrate(1:1:1) |
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Khandavilli, U.B.R.; Keshavarz, L.; Skořepová, E.; Steendam, R.R.E.; Frawley, P.J. Organic Salts of Pharmaceutical Impurity p-Aminophenol. Molecules 2020, 25, 1910. https://doi.org/10.3390/molecules25081910
Khandavilli UBR, Keshavarz L, Skořepová E, Steendam RRE, Frawley PJ. Organic Salts of Pharmaceutical Impurity p-Aminophenol. Molecules. 2020; 25(8):1910. https://doi.org/10.3390/molecules25081910
Chicago/Turabian StyleKhandavilli, U. B. Rao, Leila Keshavarz, Eliška Skořepová, René R. E. Steendam, and Patrick J. Frawley. 2020. "Organic Salts of Pharmaceutical Impurity p-Aminophenol" Molecules 25, no. 8: 1910. https://doi.org/10.3390/molecules25081910