Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Solubility and polymorphism of molecular compounds
KTH, School of Chemical Science and Engineering (CHE), Chemical Engineering and Technology, Transport Phenomena.
2005 (English)Doctoral thesis, comprehensive summary (Other scientific)
Abstract [en]

This thesis deals with the controlled crystallization of small organic molecules and is focused on solubility and polymorphism. The solubility was determined for phenylacetic acid, p-hydroxyphenylacetic acid, p-aminophenylacetic acid, p-hydroxybenzoic acid and ibuprofen in both water and in a range of organic solvents. Data is discussed from the standpoint of molecular aspects of solute – solvent interactions and by estimated solid phase activity. It was shown that better understanding could be acquired by making a qualitative analysis of the molecular interactions in the solution and the crystal structure of the compounds in question.

Solubility predictions that are carried out by the UNIFAC method are not sufficiently accurate to serve as a basis for a reliable design of a crystallization process or selection of a suitable solvent since they deviate more than 15% from experimental values. The reason for the discrepancies are related to uncertainties in the prediction of activity coefficients by UNIFAC, as well as, difficulties in the estimation of the activity of the solid state.

p-Aminobenzoic acid (PABA) has been crystallized from thirteen different solvents either by slow cooling, after which the product is allowed to mature in suspension, or by rapid cooling followed by immediate isolation. Two different polymorphs have been crystallized. The system is found to be enantiotropic with the transition temperature of 25 °C, below which the β-form is the stable polymorph. The α-form was obtained from all solvents by both methods. The β-form is obtained only in carefully controlled conditions from water and ethyl acetate, well below the transition temperature. Often the α-form appears concomitantly.

It is shown in this work that sonication significantly reduces the induction time for nucleation. The β-form crystallizes more reproducibly and at higher cooling rates when controlled sonication is used. In addition sonication is found to selectively favor the appearance of one of the polymorphs. Producing the pure β-form was possible even above the transition temperature where other crystallization techniques were only capable of producing the stable α-form. The α-form structure is based on centro symmetric dimers formed by association of carboxylic acid groups. It is suggested that the preference for nucleation of the α-polymorph is related to the formation of dimers in the supersaturated solution. Only at the condition where the formation of dimers is reduced sufficiently, (i.e. in the polar solvents or when sonication is applied) the nucleation of the β-form is favored.

Place, publisher, year, edition, pages
Stockholm: KTH , 2005. , viii, 63 p.
Series
Trita-KET, ISSN 1104-3466 ; 215
Keyword [en]
Chemical engineering, solubility, prediction of solubility, UNIFAC, activity coefficients, activity of the solid phase, polymorphism, controlled crystallization, sonication.
Keyword [sv]
Kemiteknik
National Category
Chemical Engineering
Identifiers
URN: urn:nbn:se:kth:diva-267ISBN: 91-7178-077-7 (print)OAI: oai:DiVA.org:kth-267DiVA: diva2:8350
Public defence
2005-06-17, Sal E3, Lindstedtsvägen 3, Stockholm, 12:00
Opponent
Supervisors
Note
QC 20101014Available from: 2005-06-07 Created: 2005-06-07 Last updated: 2010-10-14Bibliographically approved
List of papers
1. Solubility of Phenylacetic Acid, p-Hydroxyphenylacetic Acid, p-Aminophenylacetic Acid, p-Hydroxybenzoic Acid, and Ibuprofen in Pure Solvents
Open this publication in new window or tab >>Solubility of Phenylacetic Acid, p-Hydroxyphenylacetic Acid, p-Aminophenylacetic Acid, p-Hydroxybenzoic Acid, and Ibuprofen in Pure Solvents
2002 (English)In: Journal of Chemical and Engineering Data, ISSN 0021-9568, E-ISSN 1520-5134, Vol. 47, no 6, 1379-1383 p.Article in journal (Refereed) Published
Abstract [en]

The solubility of phenyl acetic acid, p-hydroxyphenylacetic acid, p-aminophenylacetic acid, p-hydroxybenzoic acid, and ibuprofen in water and in a range of organic solvents of relevance to industrial processing is reported. The solvents used are water, methanol, ethanol, 2-propanol, acetone, 4-methyl-2-pentanone, ethyl acetate, chloroform, and toluene. Solubility data are discussed from the standpoint of molecular aspects of solute-solvent interactions and by estimated solid-phase activity.

Keyword
Molecular dynamics, Organic solvents, Phase composition, Reaction kinetics, Solubility, Solutions, Water, Aminophenylacetic acid, Hydroxybenzoic acid, Hydrozyphenylacetic acid, Ibuprofen, Phenyl acetic acid, Solid phase activity, Solute solvent interactions
National Category
Chemical Engineering
Identifiers
urn:nbn:se:kth:diva-5293 (URN)10.1021/je0255170 (DOI)000179368500011 ()
Note
QC 20101014Available from: 2005-06-07 Created: 2005-06-07 Last updated: 2017-12-04Bibliographically approved
2. Prediction of Solubility of Solid Organic Compounds in Solvents by UNIFAC
Open this publication in new window or tab >>Prediction of Solubility of Solid Organic Compounds in Solvents by UNIFAC
2002 (English)In: Industrial & Engineering Chemistry Research, ISSN 0888-5885, E-ISSN 1520-5045, Vol. 41, no 20, 5114-5124 p.Article in journal (Refereed) Published
Abstract [en]

Predictions of solubility of nine different solid organic fine chemical compounds in water and organic solvents of relevance to industrial processing are examined. UNIFAC interaction parameters are taken from standard reference literature, extracted from liquid-vapor equilibria. For most systems, predicted solubilities deviate more than 15% from experimental values. Deviations are due to uncertainties in the estimation of the activity of the pure solid as well as to deficiencies in the estimation of activity coefficients in the solution. By comparison with results from ab initio quantum chemical calculations of the elecrostatic potential on the molecular surface of the solutes, it can be shown that a key assumption of the UNIFAC approach is not necessarily fulfilled. The properties of a functional group may depend significantly on the properties of the rest of the molecule.

Keyword
Organic compounds, Solvents, Uncertain systems, ab initio calculation, article, calculation, electricity, industry, liquid, molecule, parameter, prediction, processing, quantum chemistry, solid, solubility, solute, standard, vapor
National Category
Chemical Engineering
Identifiers
urn:nbn:se:kth:diva-5294 (URN)10.1021/ie011014w (DOI)000178283700025 ()
Note
QC 20100927 NR 20140805Available from: 2005-06-07 Created: 2005-06-07 Last updated: 2017-12-04Bibliographically approved
3. Polymorphism and Crystallization of p-Aminobenzoic Acid
Open this publication in new window or tab >>Polymorphism and Crystallization of p-Aminobenzoic Acid
2004 (English)In: Crystal Growth & Design, ISSN 1528-7483, E-ISSN 1528-7505, Vol. 4, no 5, 1013-1023 p.Article in journal (Refereed) Published
Abstract [en]

p-Aminobenzoic acid (PABA) crystallizes in two different polymorphic forms: the alpha-polymorph, which is the commercially available form and appears as long, fibrous needles, and the beta-polymorph, which appears in the form of prisms. The thermodynamic stability and crystallization from different solvents have been studied experimentally. The system is found to be enantiotropic with a transition temperature of 25degreesC, below which the beta-form is the stable polymorph. The compound has been crystallized from 13 different solvents, either by slow cooling after which the product is allowed to mature in suspension, or by rapid cooling followed by immediate isolation. Needles were obtained from all solvents by both methods. In water and in ethyl acetate, at slow cooling below 20degreesC, the prismatic beta-form is obtained, however, often together with the needles. The beta-form crystals usually needed hours or days to grow at the very slow cooling used, while needles usually appeared in seconds. By careful control of supersaturation and temperature, cooling crystallization can be performed to produce the pure beta-form in water and in ethyl acetate. The influence of the solvent is explained by analysis of the crystal structures versus the possible interaction of the solvent molecules with the solute in solution. The alpha-form structure is governed by carboxylic acid dimers and is kinetically favored since it is believed that the corresponding dimers easily form in the solution, especially in less polar solvents.

Keyword
organic-compounds, stability, solubility, nucleation, patterns, crystals
National Category
Chemical Engineering
Identifiers
urn:nbn:se:kth:diva-5295 (URN)10.1021/cg049954h (DOI)000223714000020 ()2-s2.0-4544245875 (Scopus ID)
Note
QC 20101014Available from: 2005-06-07 Created: 2005-06-07 Last updated: 2017-12-04Bibliographically approved
4. Influence of ultrasound on the nucleation of polymorphs of p-aminobenzoic acid
Open this publication in new window or tab >>Influence of ultrasound on the nucleation of polymorphs of p-aminobenzoic acid
2005 (English)In: Crystal Growth & Design, ISSN 1528-7483, E-ISSN 1528-7505, Vol. 5, no 5, 1787-1794 p.Article in journal (Refereed) Published
Abstract [en]

p-Aminobenzoic acid crystallizes in two different polymorphic forms: the alpha-form and the beta-form. The alpha-form crystals are needle-shaped, while the beta-form crystals have a more favorable prismatic shape. The system is enantiotropic with the transition temperature at approximately 25 degrees C. Below the transition temperature, the beta-form is the thermodynamically stable polymorph but can only be produced at very slow supersaturation generation either in water or in ethyl acetate. In the present work, the influence of ultrasound on the nucleation of p-aminobenzoic acid polymorphs has been investigated by use of several different sonication intensities and schemes. It is shown that sonication significantly reduces the induction time for nucleation. By using controlled sonication, we were able to more reproducibly crystallize the beta-form at more reasonable cooling rates. In addition, sonication is found to quite selectively favor the appearance of the beta-polymorph. It is even possible to produce the pure beta-form above the transition temperature where it is the metastable form and impossible to produce without sonication. The alpha-form structure is based on centro symmetric dimers formed by the association of carboxylic acid groups, while the beta-form contains four-membered hydrogen-bonded rings of alternating amino and carboxylic acid groups. It is suggested that ultrasound disturbs the building up of the dimers in the solution and thus favors the crystallization of the beta-polymorph.

Keyword
benzoic-acid, crystallization, relaxation
National Category
Chemical Engineering
Identifiers
urn:nbn:se:kth:diva-5296 (URN)10.1021/cg050056a (DOI)000231767400025 ()2-s2.0-25444515474 (Scopus ID)
Note
QC 20101014. Uppdaterad från in press till published (20101014).Available from: 2005-06-07 Created: 2005-06-07 Last updated: 2017-12-04Bibliographically approved
5. Redetermination of the beta-polymorph of p-aminobenzoic acid
Open this publication in new window or tab >>Redetermination of the beta-polymorph of p-aminobenzoic acid
2005 (English)In: Acta Crystallographica Section E: Structure Reports Online, ISSN 1600-5368, E-ISSN 1600-5368, Vol. 61, no 5, O1242-O1244 p.Article in journal (Refereed) Published
Abstract [en]

Single crystals of p-aminobenzoic acid, C7H7NO2, were grown from water. In the structure, there is one molecule of the acid present in the asymmetric unit. Hydrogen bonds between adjacent molecules lead to the formation of a three-dimensional network.

Keyword
4-aminobenzoic acid, crystal-structure
National Category
Chemical Engineering
Identifiers
urn:nbn:se:kth:diva-14721 (URN)10.1107/s160053680500961x (DOI)000228833300101 ()2-s2.0-18544390115 (Scopus ID)
Note
QC 20100525Available from: 2010-08-05 Created: 2010-08-05 Last updated: 2017-12-12Bibliographically approved
6. 4-aminophenylacetic acid
Open this publication in new window or tab >>4-aminophenylacetic acid
2005 (English)In: Acta Crystallographica Section E: Structure Reports Online, ISSN 1600-5368, E-ISSN 1600-5368, Vol. 61, no 6, O1536-O1537 p.Article in journal (Refereed) Published
Abstract [en]

Crystals of the title compound, C8H9NO2, were obtained from ethyl acetate. The structure consists of the acid in its zwitterionic form. In the crystal structure, each molecule interacts through strong N-H center dot center dot center dot O hydrogen bonds with six adjacent molecules, yielding a three-dimensional network.

National Category
Chemical Engineering
Identifiers
urn:nbn:se:kth:diva-14785 (URN)10.1107/s1600536805012754 (DOI)000229464500108 ()2-s2.0-32244447825 (Scopus ID)
Note
QC 20100525Available from: 2010-08-05 Created: 2010-08-05 Last updated: 2017-12-12Bibliographically approved
7. 4-Hydroxyphenylacetic acid
Open this publication in new window or tab >>4-Hydroxyphenylacetic acid
2005 (English)In: Acta Crystallographica Section E: Structure Reports Online, ISSN 1600-5368, E-ISSN 1600-5368, Vol. 61, no 6, O1919-O1920 p.Article in journal (Refereed) Published
Abstract [en]

The crystal structure of commercially available 4-hydroxyphenylacetic acid, C8H8O3, is non-centrosymmetric, with four hydrogen bonds between each molecule and adjacent molecules. The hydrogen bonds link the molecules in the crystal structure into an infinite three-dimensional framework.

National Category
Chemical Engineering
Identifiers
urn:nbn:se:kth:diva-14786 (URN)10.1107/s1600536805016405 (DOI)000229464500254 ()2-s2.0-32244436853 (Scopus ID)
Note
QC 20100525Available from: 2010-08-05 Created: 2010-08-05 Last updated: 2017-12-12Bibliographically approved

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Gracin, Sandra
By organisation
Transport Phenomena
Chemical Engineering

Search outside of DiVA

GoogleGoogle Scholar

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 790 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf