Karim Traboulsi 201003244 Chem 209 section 1 2-Pyridones

I.

Introduction

2-pyridone is an organic compound with a formula C5H4NH(O). It is a colorless crystalline solid often used in peptide formation. It exists as a tautomer, which are isomers that interconvert and are often assumed to be the same compound. It s amide group is similar to that of amino acid groups and it form hydrogen bonds with compounds containing Nitrogen and oxygen groups. It is a naturally occurring compound and it is integrated into various pharmaceutical compounds. 2-pyridones exhibit various biological activities including, including inotropic and vasodilatatory actions, used in the clinical treatment of heart failure. Some others even showed anti-tumor action. And some derivatives have anti-bacterial as well as virus inhibiting properties. The purpose of this synthesis: The main purpose of this procedure is making an easy way of synthesizing 2-pyridones, with the highest yields, and the lowest cost. We also can review several methods learned in Chem 209 which are Column Chromatography, Recrystallization, Reflux method, Purifying using MgSO4, and learning new methods for purification.

Synthesis reaction:

II.

Main Reactions (sequence related to procedure)

1. Preparation of dimethyl-4-(methoxymethylene)-2-pentenedioate (2a/2b)

2. Preparation of enamino ester

3. Preparation of pyridones

III.

Table of reagents and compounds encountered

Name Xylene Amine Methanol Acetyl Chloride Ether THF Hexane MgSO4 Coumalic Acid DMF (Dimethylformamide) DBU (Diazabicycloundecene) dimethyl 4-(methoxymethylene)-2pentenedioate dimethyl (2E,4Z)-4-aminomethylene-2pentenedioate (3a) dimethyl (2E,4Z)-4-[(benzylamino)methylene]-2-pentenedioate (3c)

molar mass 106.16 g/mol 32.04 g/mol 78.49 g/mol 74.12 g/mol 72.11 g/mol 86.18 g/mol 120.366 g/mol 134.06 g/mol 73.09 g/mol 152.24 g/mol 203.21 g/mol

BP ~139 C 65 C 52 C 34.6 C 66 C 68 C

MP ~20 C "-95 C"

153 C 80 C

21.41 "-112 C" mmol "-116 C" "-108.4 C" "-96 --94 C" "1124 C" 21.41 mmol "130 C" "-61 C" "-70 C" 56C 138C 108C

IV.

Procedure

Preparation of dimethyl-4-(methoxymethylene)-2-pentenedioate (2a/2b) (reaction 1)

1. Add 2.83 ml of Acetyl Chloride (21.41 mmol) by drops to 3 g of coumalic acid (21.41 mmol) in a 30 ml of Methanol over 10 min at temperature 0 Celsius. 2. reflux for 10hr in oil bath then cool to room temperature 3. dilute with ethyl acetate then wash by 30 ml of brine 4. extract with ethyl acetate (3 v30ml) 5. then filter through MgSO4 6. the purified by column chromatography (SiO2, EtOAc : n-Hexane = 1 : 5) 7. recrystallize the yield with ether/n-hexane Preparation of enamino ester (reaction 2) 1. add some amine to the mixture of 2a/2b in 5ml of THF 2. after 10 min dilute reaction with 10ml ethyl acetate 3. wash with 20 ml of brine 4. extract the aqueous phase with ethyl acetate 5. dry organic layers with MgSO4 6. filter then purify by column chromatography 7. and recrystallize in ether/n-hexane Preparation of pyridones (reaction 3) 1. reflux enanmino ester (compound 3) in 5ml of xylene under DBU catalyst with the mixture of 2a/2b in 5ml DMF 2. cool to room temperature 3. dilute with diethyl ether and wash with 20ml of brine

4. extract the reaction mixture with diethyl ether and filter through MgSo4 5. Purify by column chromatography 6. Recrystallize in ether/n-hexane V. Results

The yield of the first reaction was quite high resulting in 93% of 2a/2b in a ratio of (2a-2b to 7.3 : 1). The second reaction was aimed at fabricating a enamino ester, the main products were compounds dimethyl (2E,4Z)-4-aminomethylene-2-pentenedioate (3a) 72%, having the physical characteristics of being a solid and white in color, and dimethyl (2E,4Z)-4[(benzylamino)-methylene]-2-pentenedioate (3c) in 90% also being a solid and white in color. The final reaction led to six pyridones listed here: 4a. Methyl 6-oxo-1,6-dihydro-3-pyridinecarboxylate in 77% yield in solid form and white color y 4b. Methyl 1-butyl-6-oxo-1,6-dihydro-3-pyridinecarboxylate in 97% in an oil form and brown in color y 4c. Methyl 1-benzyl-6-oxo-1,6-dihydro-3-pyridinecarboxylate in 94% in solid form and having a white color y 4d. Methyl 6-oxo-1-(2-pyridinyl)-1,6-dihydro-3-pyridinecarboxylate in 81% in solid form and white color y 4e. Methyl 6-oxo-1-(2-pyridinyl)-1,6-dihydro-3-pyridinecarboxylate in 77% in solid form and white color

4f. Methyl 6-oxo-1-phenyl-1,6-dihydro-3-pyridinecarboxylate in 83% in solid form and white color

The theoretical yield is not present perhaps because the experimenters were not expecting these various yields and changed minor details in the experimental procedure to yield higher results. VI. Discussion

The purification methods used in this experiment are similar to the ones learned and used in our chemistry 209 class. Examples of these similar methods are MgSO4 drying, column chromatography, reflux, and recrystallization. MgSO4 is used since it readily absorbs water molecules and thus is an active drying agent. Column Chromatography is used to purify individual compounds by separating them using the stationary and mobile phase, and is a cheap and efficient method. Reflux is a method using the condensation phenomenon and the return of the condensate material to the system. Recrystallization is a method used to purify a compound when it is mixed with another impurity. This experiment doesn t specifically discuss the type of recrystallization but it does mention using ether/n-hexane as its solvent. What was so interesting is that after every step multiple purification steps were taken in order to make sure every sub-product is as pure as could be to insure the sound fabrication of our pyridones with the highest yields. Which indeed was achieved since the experimental yields were quite high.

Other methods were also used such as washing with Brine. Brine is a compound high is salt (Sodium chloride) and is used for preserving.

References: Ko, Y. (2001). A new and facile synthesis of 2-pyridones.Bull. Korean Chem., 22(2), 234-236.