What is the chemical definition of a free base?

In chemistry, a free base refers to the neutral form of a molecule, specifically an amine or another type of Lewis base. This neutral state is contrasted with its protonated, or salt, form. A Lewis base is generally a substance capable of donating an electron pair.

How is the term "free base" used differently in the pharmaceutical industry compared to its colloquial usage?

In the pharmaceutical industry, "free base" denotes the neutral chemical form of a substance, used in contrast to its salt forms like hydrochlorides, which might be preferred for stability or solubility. Colloquially, however, "free-basing" refers to the process of converting a drug's salt form into its free base form, often for the purpose of smoking it as a recreational drug.

What are some common examples of alkaloids that exist as free bases?

Alkaloids, which are naturally occurring compounds containing basic nitrogen atoms, are frequently encountered in their free base form. Common examples mentioned include nicotine, cocaine, morphine, and ephedrine, along with their related derivatives.

What is the primary distinction between a free base and a salt form of an amine in terms of chemical properties?

A key difference lies in stability and solubility. While salts of amines often exhibit greater water solubility, some alkaloids may be more stable in their ionic salt form compared to their neutral free base form.

What are common counterions used when forming amine salts, and what is a hydrochloride?

When forming salts from amines, various anions can act as counterions, including chloride, bromide, sulfate, phosphate, nitrate, acetate, oxalate, citrate, and tartrate. Specifically, when an amine undergoes an acid-base reaction with hydrochloric acid, the resulting salt is termed a hydrochloride.

Provide a chemical example illustrating the difference between a free base and its corresponding salt.

The distinction between a free base and its salt is exemplified by hydroxylamine. Its neutral, free base form is represented as NH2OH, whereas its salt form, hydroxylamine hydrochloride, is represented as NH3OH+ Cl−, indicating the protonated amine cation and the chloride anion.

Why is cocaine hydrochloride not suitable for smoking, and what makes free base cocaine smokable?

Cocaine hydrochloride, commonly known as powder cocaine, decomposes when subjected to the high temperatures of smoking, rendering it unsuitable for this method of administration. Free base cocaine, however, has a relatively low melting point of 98°C and becomes volatile above 90°C, allowing it to be vaporized and inhaled when smoked.

How does the body's blood chemistry affect the form of inhaled free-base amines?

Once inhaled free-base amines enter the bloodstream, they are rapidly transported throughout the body. However, the blood's natural buffering system, primarily involving carbonate at a physiological pH of approximately 7.4, causes these free bases to quickly revert to their protonated, or acid, form.

What is the calculated equilibrium percentage of cocaine in its acid form at physiological pH, based on its pKa?

Using the Henderson–Hasselbalch equation and assuming a pKa of 8.61 for cocaine, it is calculated that approximately 94.19% of the substance will exist in its acid (protonated) form when the blood pH is at the physiological level of 7.4.

How does Le Chatelier's principle explain the sustained presence of free-base cocaine in the brain?

Le Chatelier's principle explains that as the free-base form of cocaine crosses the blood-brain barrier and is utilized or removed, the equilibrium shifts. This continuous removal of the base form prompts the acid form circulating in the blood to convert back into the free base, ensuring a sustained supply reaches the brain.

What common adulterants are often removed from street cocaine during the freebasing process?

The process of freebasing helps to purify cocaine by removing various water-soluble adulterants that are frequently added to street-level drugs. These removed substances commonly include sugars like lactose, sucrose, glucose, mannitol, and inositol.

Compare the water solubility of free base cocaine versus cocaine hydrochloride.

Cocaine freebase exhibits very low solubility in water, approximately 1 part in 600. In contrast, cocaine hydrochloride is highly soluble in water, with a solubility ratio of about 1 part in 0.5.

Describe the chemical extraction method for preparing free base cocaine.

To prepare free base cocaine from its hydrochloride salt, an alkaline solution, such as sodium hydroxide or ammonia, is used to extract the cocaine. A non-polar solvent like diethyl ether or benzene is then added, causing the mixture to separate into layers. The cocaine dissolves in the organic layer, which is subsequently separated and evaporated to yield nearly pure, white, crumbly cocaine crystals.

What is trituration in the context of preparing free base cocaine?

Trituration is an organic chemistry technique used to prepare free base cocaine. This method involves dissolving cocaine hydrochloride in water while applying constant heat and simultaneously adding a base, like baking soda, which facilitates the conversion of the salt into its free base form.

What is the common name for the solid form of free base cocaine prepared through cooking or trituration?

When free base cocaine is prepared through methods like trituration or "cooking," it often forms a solid, rock-like substance. This resulting product is commonly known as crack cocaine, which can be smoked.

In which U.S. state was the smoking of cocaine base initially most prevalent?

Initially, the smoking of cocaine base was primarily concentrated in the state of California upon its appearance in the United States.

What marked a significant development in 1975 concerning free-basing and its related products?

The year 1975 saw the first recorded hospital admission related to problems arising from free-basing cocaine. This coincided with the commercial availability of both extraction kits and accessories specifically designed for smoking the drug.

How did the prevalence of cocaine-freebasing change between 1979 and 1982, as indicated by hospital admissions?

The use of free base cocaine saw a notable increase in its association with hospital admissions between 1979 and 1982. In 1979, only 1% of cocaine-related hospital admissions involved free base use, a figure that rose significantly to 7% by 1982.

Describe the traditional method of consuming coca leaves in South America.

Traditionally in South America, coca leaves are consumed by chewing them together with an alkaline substance known as "llipta." This substance is commonly derived from the ashes of burnt plants, shells, or limestone.

What is "coca paste," and how is it sometimes confused with cocaine freebase?

Coca paste, also referred to as cocaine base or basuco, is a substance used in South America that is often confused with cocaine freebase in North America. It is known for being inexpensive and is widely used among low-income populations in the region.

How does the chewing of betel nuts involve alkalinity and the conversion of arecoline?

When betel nuts are chewed, limestone is typically added. This alkaline substance converts the primary active ingredient, arecoline, into its freebase form. This conversion enhances the absorption of arecoline through the tissues under the tongue (sublingual absorption) into the bloodstream.

What is the significance of the image caption "Lewis bases and acids"?

The image provided is accompanied by a caption identifying it as illustrating Lewis bases and acids. This refers to a chemical theory where Lewis bases are electron-pair donors and Lewis acids are electron-pair acceptors, crucial in understanding chemical reactions involving electron sharing.

What is the primary chemical characteristic that defines a free base?

The defining chemical characteristic of a free base is that it is the neutral form of a molecule, specifically an amine or another Lewis base. This means it has not accepted a proton or otherwise become an ion.

In what way do salt formulations of amines, like hydrochlorides, differ from free bases in terms of their physical properties?

Salt formulations, such as hydrochlorides, differ from free bases primarily in their properties like water solubility and stability. Salts are often more soluble in water than their corresponding free bases, which can influence how they are formulated and administered, particularly in the pharmaceutical industry.

What is the role of an alkaline solution and a non-polar solvent in the extraction of free base cocaine?

In the preparation of free base cocaine, an alkaline solution (like sodium hydroxide or ammonia) is used to convert the cocaine hydrochloride into its free base form. A non-polar solvent (like diethyl ether or benzene) is then added, which selectively dissolves the free base cocaine, allowing it to be separated from the aqueous layer containing salts and other impurities.

How does the process of "cooking" cocaine hydrochloride relate to the formation of crack cocaine?

The process referred to as "cooking" involves heating cocaine hydrochloride in water while adding a base, such as baking soda. This process converts the cocaine hydrochloride into its free base form, which then solidifies into a rock-like substance. This resulting product is known as crack cocaine, which can be smoked.

What is the significance of the pKa value of 8.61 for cocaine in relation to its form in the body?

The pKa value of 8.61 for cocaine is significant because it determines the ratio of its ionized (acid) form to its neutral (free base) form at a given pH. At the body's physiological pH of 7.4, which is below the pKa, cocaine predominantly exists in its protonated, or acid, form (approximately 94.19%).

What is the purpose of adding an alkaline substance like limestone when chewing betel nuts?

Adding an alkaline substance like limestone when chewing betel nuts serves to convert the active compound, arecoline, into its freebase form. This chemical change enhances the absorption of arecoline through the tissues under the tongue (sublingual absorption) into the bloodstream.

How does the volatility of free base cocaine at temperatures above 90°C contribute to its method of use?

The volatility of free base cocaine above 90°C means it readily turns into a vapor at temperatures achievable by smoking. This property allows the drug to be inhaled directly into the lungs, leading to rapid absorption into the bloodstream and a quick onset of effects.

Free Base Wiki: Molecular Forms: Unpacking the Free Base Distinction

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Definition

The Neutral Form

In the realm of chemistry, a free base refers to the neutral molecular form of an amine or any other Lewis base. This designation is particularly relevant within the pharmaceutical industry, where it serves as a critical distinction from salt-based formulations, such as the commonly encountered hydrochlorides.

Many substances exhibiting this characteristic are alkaloids, including well-known compounds like nicotine, cocaine, morphine, and ephedrine, or their derivatives. Understanding the free base form is essential for comprehending their chemical behavior and physiological interactions.

Context and Contrast

The term "free base" is employed to differentiate the molecule's inherent structure from its ionic counterpart, typically formed through an acid-base reaction. While salt forms often enhance water solubility, the free base form possesses distinct properties, such as altered volatility and lipid solubility, which significantly influence absorption and administration routes.

Colloquially, the term "free-basing" has also become associated with the process of converting drug salts into their free base form, primarily for the purpose of inhalation, a practice laden with significant health risks.

Insufficient Context Warning

It is important to note that a comprehensive understanding of free bases requires consideration of factors like lipid solubility and membrane absorption characteristics. While this article provides foundational knowledge based on available data, detailed exploration of these specific properties may be limited. Further context is crucial for a complete appreciation of the subject.

Chemical Properties

Stability and Solubility

The stability of a compound can differ significantly between its free base and salt forms. Some alkaloids, for instance, exhibit greater stability when formulated as ionic salts rather than as free bases. Conversely, salt forms generally demonstrate superior water solubility compared to their free base counterparts.

The following are common counterions used to form salts with basic compounds:

Chloride (Cl⁻)
Bromide (Br⁻)
Sulfate (SO₄²⁻)
Phosphate (PO₄³⁻)
Nitrate (NO₃⁻)
Acetate (CH₃COO⁻)
Oxalate (C₂O₄²⁻)
Citrate (C₆H₅O₇³⁻)
Tartrate (C₄H4O₆²⁻)

For example, the amine hydroxylamine (NH₂OH) exists in its free base form, whereas its salt form is known as hydroxylamine hydrochloride (NH₃OH⁺ Cl⁻).

Water Solubility Comparison

The difference in water solubility between free base and salt forms is substantial and directly impacts their utility and behavior. For instance, cocaine hydrochloride exhibits high solubility in water (approximately 1 part in 0.5 parts of water). In stark contrast, cocaine free base is only slightly soluble in water (around 1 part in 600 parts of water).

Volatility and Administration

The free base form often possesses higher volatility compared to its salt form. This property is particularly relevant for substances intended for administration via inhalation. For example, cocaine hydrochloride decomposes at the high temperatures required for smoking, whereas cocaine free base, with its lower melting point (98°C) and volatility above 90°C, is readily smokable.

Freebasing: Implications

Pharmacokinetics and pH

Following inhalation, the alkaloid is absorbed into the bloodstream and distributed throughout the body. However, the physiological pH of blood (around 7.4), which is buffered by bicarbonate, rapidly converts free-base amines back into their protonated acid (salt) form. Using the Henderson–Hasselbalch equation, with a pKa of 8.61 for cocaine, it's calculated that approximately 94.19% of cocaine exists as its acid form at physiological pH.

The equilibrium between the free base and its protonated form is governed by the compound's pKa and the surrounding pH. At pH 7.4, significantly below the pKa of 8.61 for cocaine, the equilibrium heavily favors the protonated (salt) form.

However, a small fraction (approximately 5.81%) remains in the free-base state. According to Le Chatelier's principle, as this free-base form crosses the blood-brain barrier and is utilized or removed, the equilibrium shifts. The protonated form in the blood is continually converted back into the free base to replenish the depleted amount, allowing for sustained passage into the central nervous system.

Impurity Removal

The process of converting a salt to a free base can also serve to remove certain water-soluble impurities and adulterants. These often include sugars like lactose, sucrose, glucose, mannitol, and inositol, which are frequently added to street drugs. Since the free base form has low water solubility, these impurities, being more water-soluble, can be separated during the extraction process.

Preparation Methods

Chemical Extraction

The free base form of cocaine is typically prepared from cocaine hydrochloride through a chemical extraction process. This involves treating the hydrochloride salt with an alkaline solution, such as sodium hydroxide (NaOH) or ammonia (NH₃). Subsequently, a non-polar organic solvent, like diethyl ether or benzene, is added.

The mixture separates into distinct layers. The organic layer, containing the dissolved free base cocaine, is carefully isolated. Evaporation of the solvent then yields nearly pure cocaine crystals, which are characteristically white and crumbly.

Trituration Technique

An alternative method involves a technique known as trituration. In this process, cocaine hydrochloride is dissolved in water and heated. Concurrently, a base, commonly baking soda (sodium bicarbonate, NaHCO₃), is introduced. This reaction converts the hydrochloride salt into the free base form of cocaine, which precipitates as a solid "rock". This solid material is often referred to as crack cocaine when prepared for smoking.

Historical Context

Emergence and Spread

The practice of smoking cocaine base first emerged in the United States, specifically noted in California, around 1974. The initial hospital admission linked to problems arising from free-basing occurred in 1975. This same year saw the commercial availability of extraction kits and associated smoking paraphernalia.

By 1978, the distribution of these accessories had expanded from California across the entire United States. Statistical data from the period indicates a significant increase in the involvement of free-basing in cocaine-related hospital admissions: rising from 1% in 1979 to 7% by 1982.

Related Practices

Coca Leaf Chewing

In parts of South America, the traditional practice involves chewing coca leaves mixed with an alkaline substance known as "llipta." This lime-like material, typically derived from burnt plant ashes or limestone, serves to convert the primary active alkaloid, arecoline, into its free base form. This facilitates absorption directly through the oral mucosa (sublingual absorption).

Betel Nut Chewing

Similarly, the chewing of betel nuts involves the addition of limestone. This alkaline agent converts the active compound, arecoline, into its free base form. This process enhances the absorption of arecoline, allowing it to be effectively taken up by the body, primarily through the lining of the mouth.

Coca Paste (Basuco)

Coca paste, often referred to as "basuco" in South America, is sometimes confused with cocaine freebase. It is a less refined product derived from the initial processing of coca leaves. Coca paste is relatively inexpensive and is widely consumed by lower-income populations in South America. Its consumption carries significant health risks.

References

^ Pubchem. "Cocaine". pubchem.ncbi.nlm.nih.gov. Archived from the original on 2018-02-18. Retrieved 2018-02-18.
^ Marian W. Fischman (1984), "The Behavioral Pharmacology of Cocaine in Humans" (PDF), in John Grabowski (ed.), Cocaine: Pharmacology, Effects, and Treatment of Abuse, NIDA Research Monograph, vol. 50, U.S. Dept. of Health and Human Services, pp. 72–91, archived from the original (PDF) on 2015-07-23, retrieved 2020-07-01
^ ^a ^b Ronald K. Siegel (1985), "New Patterns of Cocaine Use: Changing Doses and Routes", in Nicholas J. Kozel; Edgar H. Adams (eds.), Cocaine Use in America: Epidemiologic and Clinical Perspectives (PDF), NIDA Research Monograph, vol. 61, U.S. Dept. of Health and Human Services, pp. 204–222, archived from the original (PDF) on 2016-10-09, retrieved 2016-04-09
^ VV Pillay (2013), Modern Medical Toxicology (4th ed.), Jaypee, pp. 553–554, ISBN 978-93-5025-965-8
^ A. Arif, ed. (1987), Adverse health consequences of cocaine abuse (PDF), World Health Organization, archived (PDF) from the original on 2016-10-09, retrieved 2016-04-13
^ Robert C. Petersen (1977), "History of Cocaine", in Robert C. Petersen; Richard C. Stillman (eds.), Cocaine: 1977 (PDF), NIDA Research Monograph, vol. 13, U.S. Dept. of Health and Human Services, pp. 17–34, archived from the original (PDF) on 2016-03-03, retrieved 2016-04-09

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This page was generated by an Artificial Intelligence and is intended for informational and educational purposes solely within the context of chemistry and pharmacology. The content is derived from a snapshot of publicly available data from Wikipedia and may not be entirely comprehensive, accurate, or up-to-date. It does not reflect the most current scientific understanding or clinical practices.

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Molecular Forms: Unpacking the Free Base Distinction

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Definition ℹ️

⚛️ The Neutral Form

⚖️ Context and Contrast

⚠️ Insufficient Context Warning

Chemical Properties 🔬

⚖️ Stability and Solubility

💧 Water Solubility Comparison

💨 Volatility and Administration

Freebasing: Implications 💨

🧠 Pharmacokinetics and pH

🚫 Impurity Removal

Preparation Methods ⚙️

⚗️ Chemical Extraction

🔥 Trituration Technique

Historical Context ⏳

📜 Emergence and Spread

Related Practices 🔗

🍃 Coca Leaf Chewing

🌰 Betel Nut Chewing

⚠️ Coca Paste (Basuco)

References 📚

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📜 Important Notice

Dive in with Flashcard Learning!

Definition

The Neutral Form

Context and Contrast

Insufficient Context Warning

Chemical Properties

Stability and Solubility

Water Solubility Comparison

Volatility and Administration

Freebasing: Implications

Pharmacokinetics and pH

Impurity Removal

Preparation Methods

Chemical Extraction

Trituration Technique

Historical Context

Emergence and Spread

Related Practices

Coca Leaf Chewing

Betel Nut Chewing

Coca Paste (Basuco)

References

Teacher's Corner

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References

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