SED Solubility Research

Solubility of Ugi products and organic compounds in Non-aqueous solvents
by
Shuba Dumpala
Drexel University
Philadelphia, PA 19104

Abstract

The Research work on solubility of Ugi products working under the supervision of Dr. Jean-Claude Bradley at Drexel University, was a great experience. I put more emphasis on testing the solubility of different Ugi products using six different solvents, such as: Methanol, Ethanol, Acetonitrile, Toluene, Tetrahydrofuran(THF), and Dimethyl Sulfoxide (DMSO), while performing several experiments, by applying the Nuclear Magnetic Resonance (NMR) spectroscopy. Thereafter, the NMR spectra that I obtained, were compiled in JCAMP(Joint Committee on Atomic and Molecular Physical data), a standard format for NMR. These experiments are displayed publicly on Open Note Book Science Challenge on the wikispaces website, for free viewing and is unlatched from regular restrictions of laboratory research. This Research paper provides the details of the solubility determination steps, the solvents and solute compounds used, the solubility data, and the purpose of the experiment. The data collected was incorporated into a lab-note book on timely basis, while performing the experiments systematically, by following a procedure.

Introduction

My name is Shuba Dumpala and I am a senior Chemistry Major student at Drexel University. I have been performing this challenging processes of dissolving the organic compounds including Ugi products during the Spring term of 2009. The experiments involved a wide variety of procedures such as solvent extraction, vortexing, sonication, and centrifugation that required accurate data of solubilities of the compounds. The most interesting fact in my Research project under the inspiring supervision of Dr.Bradley during the Spring Quarter 2009, was that the data achieved were experimentally determined and compared with the solubility of other experiments. Dr. Bradley’s Ugi Products helped me in finding the novel anti-malarial compounds with a proven insight to determine solubilties of the compounds.
In my 10-week of my experience in Dr.Bradley’s research program, I have learned about the processes of solubility of Ugi and other organic compounds. I was encouraged to perform the experiments by Dr. Bradley and his Research scholar Khalid, who coordinated with me on many occasions. Eventually, I learned application procedures in practical Organic Chemistry, by using advanced instruments and technology at a molecular level. My experience at ONS Useful Chem involvement was of great interest, as I learned the solubility of different compounds, specially carboxylic acids, in six different solvents, such as: Methanol, Ethanol, Acetonitrile, THF,Toluene and DMSO, by NMR spectroscopy.
This presentation attempts to highlight the competing processes and limitations of some of the common solvents that are used for dissolving the Ugi products.The aim of this Research work is not only to help recognize the potential problems of the experiment, but also to inspire,challenge, and motivate new researchers to strive for the successful attempts to use the Exp216 products, specifically Ugi 3 and Ugi 4 in Exp076.

Experimental Procedure

A standard procedure was followed in the experiments that I performed which are explained below:
First, six of one or half dram clean and dry vials were neatly labeled and a small quantity of the carboxylic acid was inserted into it. The vials were labeled as 1-6 or A-F. Next, the six major solvents such as: Methanol, Ethanol, Acetonitrile, Toluene, THF, and DMSO were introduced into the vials. Next, the vials were vortexed and later sonicated for about half an hour. A thermometer was placed between the vials at the beginning and at the end of the sonication process, in order to record the temperatures of the vials. Next, pictures of the vials were taken whenever required, as a record. Later, the vials were centrifuged in order to identify and separate the solute from the solvent. Next, after centrifugation, the supernatant was extracted from the vials into new clean labeled vials with an addition to 0.7 mL of chloroform to it. The clear solution of the supernatant was extracted from the new vials and placed into six clean and dry test-tubes. Then the test-tubes with the clear homogeneous solution was taken for NMR test, which took for about 45-60 minutes. I assisted Khalid in performing the NMR test. The calculations and data were incorporated into Google spreadsheet as exemplified in Google Spreadsheet and were publicly displayed on the ONS webpage, where it is easily accessible.
I performed five different experiments, Exp075, Exp076, Exp081, Exp087, and Exp090, with different carboxylic acids such as 4-chlorophenylacetic acid, diphenylacetic acid, 2,4,6-Trihydroxy benzoic acid, 2,3-dihydroxybenzoic acid and UGI products such as Ugi 3 and Ugi216-4. The experiments were aimed at achieving accurate results through trial and error strategies. Experiments such as Exp076 and Exp090 had to be aborted because the NMR could not be determined for these experiments. In Exp087, the compound 2,4,6-Trihydroxy benzoic acid was discovered to be a monohydrate. Hence, the NMR was impossible to perform for this experiment because two layers formed with CDCl3.

Discussion

Exp075: The estimation of solubility of 4-chlorophenylacetic acid in four solvents by NMR spectroscopy.
4-chlorophenyl_acetic_acid-2.jpg
4-chlorophenylacetic acid
I observed that the solute 4-chlorophenylacetic acid was soluble at 2.41M in acetonitrile. The concentrations of Acetonitrile of Exp04(1.29M and 1.32M)with that of Exp075(2.41M) varied to a great extent. Acetonitrile is better that 0.89M Toluene.However, 5.02 M THF and 5.74 M DMSO had greater concentrations than acetonitrile.
4-chlorophenyl_acetic_acid.jpg

The observed value of the concentration of the sample in Exp075 was closer to the actual value because the base-line and peaks of the Exp075 were much sharper than that of Exp04.

Exp076: The estimation of solubility of unknown Ugi products in six solvents by
using NMR spectroscopy.
UC216-3A.jpgUC216-4Ajpg.pngUC 216-4A

UC 216-3A
Ugi products

The results of the NMR spectroscopy for the solubility of UC 216 4A and UC2163A performed by other students in the past with 0.12M acetonitrile and 0.6M DMSO were not accurate due to the distortions in the peaks.
In Exp076,the NMR results of the Ugi products,UC216-3A and UC216-4A were
unclear due to distortions in the peaks. Hence, the experiment had to be aborted.

Exp081: Determination of solubility of diphenyl acetic acid in methanol, ethanol, acetonitrile, THF, Toluene and DMSO.
I observed that the solute diphenylacetic acid was more soluble in 1.36M in Exp077 compared to 1.18M Methanol in Exp081.The concentrations of the solvent methanol between Exp077 and Exp081 varied to a great extent. The concentration of the Ethanol was 1.15M, Acetonitrile- 0.46M and Toluene- 0.71M, which were all less than Methanol. The concentration of DMSO was 2.56M and the concentration of THF was 2.91M, which were greater than that of methanol.

diphenylacetic_acid.jpg
diphenylacetic_acid-2.jpg
Diphenylacetic acid
It was concluded that the concentration of Exp081,which was 1.18, was closer to the actual value. The base-line and peaks of the present experiment Exp081were much sharper than Exp077.
Exp087: Determination of solubility of 2,4,6-Trihydroxy benzoic acid in the six major solvents by NMR spectroscopy.
2,4,6-trihydroxybenzoic_acid.jpg
2,4,6-trihydroxy benzoic acid
In this experiment, it was observed that the compound 2,4,6-trihydroxy benzoic acid was a ‘monohydrate'. This happened while performing the centrifugation. Further, because of the chemical interactions that include 'Hydrogen Bonding,' it was concluded that NMR test was impossible to perform for this experiment.

Exp090: Determination of the solubility of 2,3-dihydroxybenzoic acid in the six major solvents.
2,3-dihydroxybenzoic_acid.jpg
2,3-dihydroxybenzoic acid
In this experiment with the compound 2,3-dihydroxybenzoic acid, the contents was contaminated and the solution was not clear to be tested for NMR. Consequently, a reaction had occured.For instance, two layers formed when CDCl3 was added to it. Hence, the experiment had to be aborted as the NMR test could not be performed. All the above experiments followed the same procedure as explained above.

Conclusion

The strategies for avoiding possible solute-solvent reactions were implemented in these experiments. The main focus was to choose the right solvents based on the nature of the organic compounds. THF was found to be more suitable for dissolving diphenyl acetic acid because of hydrogen bonding. Similarly , 4-Chloro phenyl acetic acid was found to be highly soluble in DMSO. Thus the best solvents that I found were THF and DMSO.
I was thrilled to learn how to perform the procedures of vortexing, sonication, centrifugation and to take the NMR test in labs. I learned to incorporate experimental data into the ONS webpage, perform calculations and learn from other students in the laboratory. Overall , my experience in this research has sharpened my knowledge in organic chemistry with the excellent motivation of my Professor Dr.Bradley, who had guided me to perform experiments and achieve accurate results. In future, I wish to continue my research work in the solubility experiments since I am interested to study the solubities, stablities and other important properties of drugs and pharmaceuticals.

Tags
4-chlorophenylacetic acid
InChI=1/C8H7ClO2/c9-7-3-1-6(2-4-7)5-8(10)11/h1-4H,5H2,(H,10,11)
InChIKey: CDPKJZJVTHSESZ-UHFFFAOYAC
Ugi Product 216-4A
InChI=1/C28H40N2O7/c1-17-10-12-19(36-17)15-20(21(31)16-29-26(33)37-28(5,6)7)24(25(32)30-27(2,3)4)18-11-13-22(34-8)23(14-18)35-9/h10-14,20,24H,15-16H2,1-9H3,(H,29,33)(H,30,32)
InChIKey: QTFHBEDSKOMZFW-UHFFFAOYAU
Diphenylacetic acid
InChI=1/C14H12O2/c15-14(16)13(11-7-3-1-4-8-11)12-9-5-2-6-10-12/h1-10,13H,(H,15,16)
InChIKey: PYHXGXCGESYPCW-UHFFFAOYAC
2,4,6-trihydroxybenzoic acid
InChI=1/C7H6O5/c8-3-1-4(9)6(7(11)12)5(10)2-3/h1-2,8-10H,(H,11,12)
InChIKey: IBHWREHFNDMRPR-UHFFFAOYAP
2,3-dihydroxybenzoic acid
InChI=1/C7H6O4/c8-5-3-1-2-4(6(5)9)7(10)11/h1-3,8-9H,(H,10,11)
InChIKey: GLDQAMYCGOIJDV-UHFFFAOYAE

References
http://onschallenges.wikispaces.com/Exp097
www. acdlabs.com/publish/jcamp.html
http://usefulchem.blogspot.com/
http://www.scribd.com/search?cx=007890693382555206581%3A7fgc6et2hmk&cof=FORID%3A10&ie=UTF-8&q=Solubilty+of+UC+216+3A+antimalaria++products&sa=Search#1501
http://onschallenge.wikispaces.com