Syntheses, Crystallization, and Spectroscopic Characterization of 3,5-Lutidine N-Oxide Dehydrate

Summary

Herein, we report the synthesis and crystallization of 3,5-lutidine N-oxide dehydrate by a simple protocol that differs from the classical synthesis of pyridine N-oxide. This protocol utilizes different starting material and involves less reaction time to yield a new solvated supramolecular structure, which crystallizes under slow evaporation.

Abstract

The synthesis of 3,5-lutidine N-oxide dehydrate, 1, was achieved in the synthesis route of 2-amino-pyridine-3,5-dicarboxylic acid. Ochiai first used the methodology for non-substituted pyridines in 1957 in a 12 h process, but no X-ray suitable crystals were obtained. The substituted ring used in the methodology presented here clearly influenced the addition of water molecules into the asymmetric unit, which confers a different nucleophilic strength in 1. The X-ray suitable crystal compound 1 was possible due to the stabilization of the negative charge in the oxygen by the presence of two water molecules where the hydrogen atoms donate positive charge into the ring; such water molecules serve well to construct a supramolecular interaction. The hydrated molecules may be possible for the alkaline system that is reached by adjusting the pH to 10. Importantly, the double methyl substituted ring and a reaction time of 5 h, makes it a more versatile method and with wider chemical applications for future ring insertions.

Introduction

Nowadays, scientists around the globe have been investing resources into the development of new synthetic routes for the functionalization of aromatic groups, which are known for low reactivity front to addition reactions^1,2,3. Pyridine, where a nitrogen atom substitutes a carbon atom, presents a similar chemical reactivity to analogue rings composed solely of carbon atoms³, and it usually undergoes a substitution mechanism rather than addition. N-oxides are distinctive by the presence of a donor bond between nitrogen and oxygen formed by the ....

Protocol

1. Reaction

1. Place in a fume hood an opened round 100 mL flask with 0.5 mol (29.8 mL) glacial acetic acid and add 0.051 mol (5.82 mL) of 3,5-dimethylpyridine and 5 mL of H₂O₂ (35%). Keep the mixture reaction under constant magnetic stirring, at an inner temperature of 80 °C for 5 h.
2. After the reaction time, cool the flask to 24 °C with ice (do not expose the acetic acid gases to the ice), and plug it to a high vacuum distillation unit for 90-120 min to remove excess acetic acid.
   Caution: Do not use hot material. Wait until the glassware reaches a manageable temperature. This will also avoid vapors entering th....

Results

The protocol is essentially an extension of Ochiai's technique¹. However, lower temperature and less time are applied. This simple method can be used to obtain a versatile ligand, which is a substituted pyridine N-oxide derivate. To confirm the formation of 1, NMR ¹H and ¹³C analysis are preferred to test the effectiveness of the procedure.

The chemical shif.......

Discussion

The protocol presented here is a conventional method to link an oxygen atom to the nitrogen atom of the 3,5-lutidine as a functionalization method of substrates. This technique is also well established to yield X-ray suitable dehydrated crystals (Figure 5, pictures taken with a DSC-HX300 Cyber-shot Sony camera). As far as we are concerned, not many reports have described the production of such crystals¹⁶. Many compounds grow ideal crystals for X-ray analysis when they are chelated.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
3,5-lutidine	Sigma-Aldrich	L4206-500ML
Glacial acetic acid	Fermont	3015
Hidrogen peroxide (35%)	Sigma-Aldrich	349887-500ML
Na2CO3 anhydrous	Productos Químicos Monterrey	1792
Na2SO4 anhydrous	Alfa reactivos	25051-C
CHCl3	Fermont	6205
Ethyl eter	Mercury Chemist	QME0309
Distilled water	Comercializadora Química Poblana	not-existent