Caffeine

Gene A. Spiller

• Publisher: CRC Press
• Year: 2019
• Print ISBN: 9780849326479
• eBook ISBN: 9780429525582
• Topic: Medicine
• Subtopic: Nutrition, Dietics & Bariatrics

Caffeine-found in tea, coffee, mate, cola beverages, cocoa, and chocolate products-is an integral part of the diet of many people. Caffeine answers questions for a broad range of readers interested in the effects beverages and foods containing this dietary methylxanthine have on human health, nutrition, and physiological functioning. The composition, processing, consumption, health effects, and epidemiological correlations of caffeine are examined in detail. It is often said that too much caffeine is "bad for you." How much is too much? Get the facts on consumption of caffeine-containing products with this authoritative text. Chapters 1 and 2 offer an introductory, concise overview of the chemistry and analysis of methylxanthines. In Chapters 3 through 8, each natural product-tea, coffee, mate, and cocoa and chocolate products-is described in terms of botany, cultivation, processing, composition, and consumption patterns. Consumption of caffeine is also examined in detail in Chapter 9. Chapter 10 provides an easy-to-read overview of the basic physiology and biochemistry of caffeine. The ergogenic, cognitive, and emotional effects of caffeine are discussed in Chapters 11 and 12. Chapters 13 through 16 deal with specific health effects-serum cholesterol, cancer and fibrocystic breast disease, calcium and bone health, and human reproduction. For physicians, nutritionists, other health professionals, food scientists, and everyone interested in the effects of caffeine on the human body, Caffeine is a convenient, single-source reference.

Chapter 1

INTRODUCTION TO THE CHEMISTRY, ISOLATION, AND BIOSYNTHESIS OF METHYLXANTHINES

Stanley M. Tarka, Jr and W. Jeffrey Hurst

CONTENTS

I.	Introduction
II.	Physical and Chemical Properties of the Methylxanthines
	A. Organoleptic Properties
	B. Melting and Sublimation Temperatures
	C. Solution Formation
	D. Ultraviolet and Infrared Absorption
	E. Complex Formation
	F. Acidic and Basic Equilibria
III.	Isolation of the Methylxanthines
IV.	Biosynthesis of the Methylxanthines
	A. In Coffee
	B. In Tea
	C. In Cacao
References

I. INTRODUCTION

The methylxanthines of interest are caffeine (1,3,7-trimethylxanthine), theophylline (1,3-dimethylxanthine), and theobromine (3,7-dimethylxanthine) and they occur in coffee, tea, maté, cocoa products, and cola beverages. This chapter is an introduction to their chemistry, isolation, and biosynthesis. While the class of methylxanthines is large and comprised of more members than these three, this chapter will essentially be limited to caffeine, theobromine, and theophylline.

Purine is the parent heterocyclic compound of the methylxanthines, which are often referred to as the purine alkaloids.^{1,2,3,4,5,6,7} Purine is also the parent compound of some of the base constituents of the nucleotides, which in turn are part of the nucleic acids RNA and DNA. Thus, it appears that the purine alkaloids have similar precursors to nucleic acids.

II. PHYSICAL AND CHEMICAL PROPERTIES OF THE METHYLXANTHINES

A. Organoleptic Properties

Caffeine, as an example methylxanthine, is a colorless powder at room temperature; it is odorless but does have a slightly bitter taste.⁸

B. Melting and Sublimation Temperatures

The trimethylated xanthine, caffeine, sublimes at 1800°C, which is a lower temperature of sublimation than theobromine.¹⁰ Temperatures of melting and sublimation are given in Table 1.

C. Solution Formation

Solubility values are distinctive for caffeine, theobromine, and theophylline (see Table 2). Caffeine dissolves well in boiling water, but at room temperature chloroform is one of the best solvents. Theobromine is generally much less soluble than caffeine but it will dissolve readily in aqueous acids and alkalis. Theophylline is intermediate between caffeine and theobromine in its ability to form solutions. A series of studies were conducted by Hockfield¹⁷ and Gilkey,¹⁸ who, after comparing the solubility rates of the xanthine alkaloids, determined that the methylxanthines in which both heterocyclic nitrogen atoms in the ring are methylated (caffeine and theophylline) display a much greater solubility in polar solvents than those with at least one unmethylated nitrogen atom (theobromine).

TABLE 1
Melting and Sublimation Temperatures for Methylxanthines

Compound	Sublimation point (°C)	Melting point (°C)
Caffeine	180^8	236.5 under pressure^8
	178^9	238^9
	178^7	235 anhydrous^7
Theobromine	290–295^9	357^9
	290^7	330 sealed tube^7
Theophylline	—	270–274^9
	269–272^7

TABLE 2
Solubility Values for Methylxanthines

Solvent	Caffeine (%)	Theobromine (%)	Theophylline (%)
Water, 150°C	1.3^8
Water	2.2^9	0.005^9	0.83^9
Water, 400°C	4.6^8
Water, hot		Soluble^9
Water, 800°C	18.2^9
Water, boiling	66.7^9	0.67^9
Ether	0.3^8	Almost insol.^9	Sparingly sol.^9
	0.2^9
Alcohol	1.2^8	1.25^9
	1.5^9
Alcohol, 600°C	4.5^9
95% Alcohol	0.045^9
Ethyl acetate	2.5^8
Chloroform	13.0^8	Almost insol.^9	0.91^9
	18.2^9
Acetone	2.0^9
Benzene	1.0^9	Almost insol.^9
Benzene, boiling	4.5^9
Pyrrole	Freely sol.^9
Tetrahydrofuran and 4% water	Freely sol.^9
Petroleum ether	Sparingly sol.^9
Carbon tetrachloride		Almost insol.^9

These studies indicate that intermolecular hydrogen bonding between lactam systems in the nonmethylated alkaloids is responsible for these differences. The findings indicate a difference between the enthalpies of theobromine, which would be expected to form a dimer, and those of caffeine and theophylline, whose structures would preclude dimerization, is approximately that of one hydrogen bond per molecule.

D. Ultraviolet and Infrared Absorption

The methylxanthines show useful strong ultraviolet (UV) absorption between 250 and 280 nm.¹¹ The spectra for the methylxanthines are very similar and only when one uses techniques such as derivative spectroscopy can substantial differences be seen. In addition to the UV absorption, the methylxanthines also exhibit strong infrared (IR) spectra which can provide critical information about these compounds.

E. Complex Formation

In aqueous solution, caffeine associates to form at least a dimer and probably a polymer;¹² the molecules are arranged in a stack.¹³ Caffeine will also associate with purines and pyrimidines either as the free bases or as their nucleosides.¹³ Caffeine crystallizes from water as a monohydrate [9].

Chlorogenic acid forms a 1:1 complex with caffeine, which can be crystallized from aqueous alcohol and yields very little free caffeine on extraction with chloroform. Other compounds with which caffeine will complex in this way include isoeugenol, coumarin, indole-acetic acid, and anthocyanidin. The basis for this selection was the requirement for a substituted aromatic ring and a conjugated double bond in forming such a complex. This kind of complex does modify the physiological effects of caffeine.¹⁴ Complex formation will also increase the apparent aqueous solubility of caffeine in the presence of alkali benzoates, cinnamates, citrates, and sali...

Table of contents

• Cover
• Title Page
• Copyright Page
• Dedication
• Table of Contents
• Chapter 1 Introduction to the Chemistry, Isolation, and Biosynthesis of Methylxanthines
• Chapter 2 Analytical Methods for Quantitation of Methylxanthines
• Chapter 3 Tea: The Plant and Its Manufacture; Chemistry and Consumption of the Beverage
• Chapter 4 Tea in China
• Chapter 5 The Coffee Plant and Its Processing
• Chapter 6 The Chemical Components of Coffee
• Chapter 7 Methylxanthine Composition and Consumption Patterns of Cocoa and Chocolate Products
• Chapter 8 Maté
• Chapter 9 Caffeine Consumption
• Chapter 10 Basic Metabolism and Physiological Effects of the Methylxanthines
• Chapter 11 Caffeine as an Ergogenic Aid
• Chapter 12 Caffeine: Effects on Psychological Functioning and Performance
• Chapter 13 Coffee, Caffeine, and Serum Cholesterol
• Chapter 14 Coffee, Tea, Cancer and Fibrocystic Breast Disease
• Chapter 15 Caffeine, Calcium, and Bone Health
• Chapter 16 Caffeine and Reproduction
• Appendix I Caffeine Content of Some Cola Beverages
• Index