Crystal design approaches for the synthesis of paracetamol co-crystals

Crystal engineering principles were used to design three new co-crystals of paracetamol. A variety of potential cocrystal formers were initially identified from a search of the Cambridge Structural Database for molecules with complementary hydrogen-bond forming functionalities. Subsequent screening by powder X-ray diffraction of the products of the reaction of this library of molecules with paracetamol led to the discovery of new binary crystalline phases of paracetamol with trans-1,4- diaminocyclohexane (1); trans-1,4-di(4-pyridyl)ethylene (2); and 1,2-bis(4-pyridyl)ethane (3). The co-crystals were characterized by IR spectroscopy, differential scanning calorimetry, and 1H NMR spectroscopy. Single crystal X-ray structure analysis reveals that in all three co-crystals the co-crystal formers (CCF) are hydrogen bonded to the paracetamol molecules through O−H···N interactions. In co-crystals (1) and (2) the CCFs are interleaved between the chains of paracetamol molecules, while in co-crystal (3) there is an additional N−H···N hydrogen bond between the two components. A hierarchy of hydrogen bond formation is observed in which the best donor in the system, the phenolic O−H group of paracetamol, is preferentially hydrogen bonded to the best acceptor, the basic nitrogen atom of the co-crystal former. The geometric aspects of the hydrogen bonds in co-crystals 1−3 are discussed in terms of their electrostatic and charge-transfer components

A robust two-dimensional hydrogen-bonded network for the predictable assembly of ternary co-crystals of furosemide

Consideration of the geometrical features of the functional groups present in furosemide has enabled synthesis of a series of ternary co-crystals with predictable structural features, containing a robust asymmetric two-dimensional network

Crystal Design Approaches for the Synthesis of Paracetamol Co-Crystals

Crystal engineering principles were used to design three new co-crystals of paracetamol. A variety of potential co-crystal formers were initially identified from a search of the Cambridge Structural Database for molecules with complementary hydrogen-bond forming functionalities. Subsequent screening by powder X-ray diffraction of the products of the reaction of this library of molecules with paracetamol led to the discovery of new binary crystalline phases of paracetamol with <i>trans</i>-1,4-diaminocyclohexane (<b>1</b>); <i>trans</i>-1,4-di­(4-pyridyl)­ethylene (<b>2</b>); and 1,2-bis­(4-pyridyl)­ethane (<b>3</b>). The co-crystals were characterized by IR spectroscopy, differential scanning calorimetry, and ¹H NMR spectroscopy. Single crystal X-ray structure analysis reveals that in all three co-crystals the co-crystal formers (CCF) are hydrogen bonded to the paracetamol molecules through O–H···N interactions. In co-crystals (<b>1</b>) and (<b>2</b>) the CCFs are interleaved between the chains of paracetamol molecules, while in co-crystal (<b>3</b>) there is an additional N–H···N hydrogen bond between the two components. A hierarchy of hydrogen bond formation is observed in which the best donor in the system, the phenolic O–H group of paracetamol, is preferentially hydrogen bonded to the best acceptor, the basic nitrogen atom of the co-crystal former. The geometric aspects of the hydrogen bonds in co-crystals <b>1</b>–<b>3</b> are discussed in terms of their electrostatic and charge-transfer components

Crystal Design Approaches for the Synthesis of Paracetamol Co-Crystals

Crystal engineering principles were used to design three new co-crystals of paracetamol. A variety of potential co-crystal formers were initially identified from a search of the Cambridge Structural Database for molecules with complementary hydrogen-bond forming functionalities. Subsequent screening by powder X-ray diffraction of the products of the reaction of this library of molecules with paracetamol led to the discovery of new binary crystalline phases of paracetamol with <i>trans</i>-1,4-diaminocyclohexane (<b>1</b>); <i>trans</i>-1,4-di­(4-pyridyl)­ethylene (<b>2</b>); and 1,2-bis­(4-pyridyl)­ethane (<b>3</b>). The co-crystals were characterized by IR spectroscopy, differential scanning calorimetry, and ¹H NMR spectroscopy. Single crystal X-ray structure analysis reveals that in all three co-crystals the co-crystal formers (CCF) are hydrogen bonded to the paracetamol molecules through O–H···N interactions. In co-crystals (<b>1</b>) and (<b>2</b>) the CCFs are interleaved between the chains of paracetamol molecules, while in co-crystal (<b>3</b>) there is an additional N–H···N hydrogen bond between the two components. A hierarchy of hydrogen bond formation is observed in which the best donor in the system, the phenolic O–H group of paracetamol, is preferentially hydrogen bonded to the best acceptor, the basic nitrogen atom of the co-crystal former. The geometric aspects of the hydrogen bonds in co-crystals <b>1</b>–<b>3</b> are discussed in terms of their electrostatic and charge-transfer components

Crystal Design Approaches for the Synthesis of Paracetamol Co-Crystals

Crystal engineering principles were used to design three new co-crystals of paracetamol. A variety of potential co-crystal formers were initially identified from a search of the Cambridge Structural Database for molecules with complementary hydrogen-bond forming functionalities. Subsequent screening by powder X-ray diffraction of the products of the reaction of this library of molecules with paracetamol led to the discovery of new binary crystalline phases of paracetamol with <i>trans</i>-1,4-diaminocyclohexane (<b>1</b>); <i>trans</i>-1,4-di­(4-pyridyl)­ethylene (<b>2</b>); and 1,2-bis­(4-pyridyl)­ethane (<b>3</b>). The co-crystals were characterized by IR spectroscopy, differential scanning calorimetry, and ¹H NMR spectroscopy. Single crystal X-ray structure analysis reveals that in all three co-crystals the co-crystal formers (CCF) are hydrogen bonded to the paracetamol molecules through O–H···N interactions. In co-crystals (<b>1</b>) and (<b>2</b>) the CCFs are interleaved between the chains of paracetamol molecules, while in co-crystal (<b>3</b>) there is an additional N–H···N hydrogen bond between the two components. A hierarchy of hydrogen bond formation is observed in which the best donor in the system, the phenolic O–H group of paracetamol, is preferentially hydrogen bonded to the best acceptor, the basic nitrogen atom of the co-crystal former. The geometric aspects of the hydrogen bonds in co-crystals <b>1</b>–<b>3</b> are discussed in terms of their electrostatic and charge-transfer components