Introduction

2,5-Dimethoxy-4-bromoamphetamine (DOB), CAS 64638-07-9, is commonly known as DOB, is the potent psychedelic compound from the substituted amphetamine class, notable for its powerful serotonergic activity. It is structurally derived from phenethylamine and exhibits a close relationship to other psychedelic substances such as DOM (2,5-dimethoxy-4-methylamphetamine) and 2C-B (4-bromo-2,5-dimethoxyphenethylamine). The defining feature of DOB is the presence of two methoxy groups at the 2- and 5-positions of the aromatic ring and a bromine atom at the 4-position, in combination with an alpha-methylated side chain typical of amphetamines. This structural configuration results in high affinity and agonistic activity at serotonin receptors—particularly the 5-HT₂A receptor—underpinning its potent hallucinogenic effects.

DOB was first synthesized in the 1960s by the chemist Alexander Shulgin, who extensively documented its synthesis and psychoactive properties in his book PiHKAL: A Chemical Love Story. Among the compounds he investigated, DOB stood out due to its long duration of action, high potency, and distinct pharmacological properties. Active in doses as low as 3 milligrams, DOB can produce profound alterations in perception, cognition, and sensory experience for up to 20–30 hours. Despite its powerful psychoactivity, DOB is not commonly found in recreational drug markets due to its long onset and challenging dose-response characteristics, which make it risky in uncontrolled settings.

In addition to its role in psychoactive research, DOB has found use as a pharmacological tool in neuroscience, particularly for the study of serotonergic systems, as a selective partial agonist of 5-HT₂A and 5-HT₂C receptors.

DOB is classified as a Schedule I substance in the United States and similarly controlled in many countries. Unauthorized possession, synthesis, or distribution is illegal and subject to prosecution.

Physical and Chemical Properties of DOB

2,5-Dimethoxy-4-bromoamphetamine (DOB), CAS Number 64638-07-9, is a synthetic compound belonging to the class of substituted amphetamines. It possesses a molecular formula of C₁₁H₁₆BrNO₂ and a molecular weight of 274.15 g/mol. The hydrochloride salt of 2,5-dimethoxy-4-bromoamphetamine has a molecular weight of 310.62 g/mol. Hydrochloride salt of 2,5-dimethoxy-4-bromoamphetamine typically appears as an off-white to beige crystalline solid. The compound has a melting point ranging between 207°C and 208°C. DOB hydrochloride—the most common form for laboratory and analytical use—displays slightly higher thermal stability and enhanced solubility. The compound is sparingly soluble in water but readily dissolves in common organic solvents such as ethanol, methanol, and dimethyl sulfoxide (DMSO).

From a structural perspective, DOB features a phenyl ring substituted at positions 2 and 5 with methoxy groups (-OCH₃), and a bromine atom at the 4-position. Attached to this aromatic ring is an amphetamine-type side chain with a primary amine group (–NH₂) on a β-carbon next to a methyl group. The bromine atom, a heavy halogen, contributes to DOB’s high binding affinity for 5-HT₂A serotonin receptors, which is a key determinant of its psychedelic potency. The presence of methoxy substituents exerts an electron-donating effect, increasing aromatic electron density and influencing reactivity patterns. Additionally, DOB is a chiral molecule; the two enantiomers differ in their pharmacological activity, with the (R)-enantiomer being significantly more active at the 5-HT₂A receptor.

Chemically, DOB exhibits stability under standard storage conditions, though it is sensitive to prolonged exposure to light, air, and acidic or basic environments. For example, demethylation of the methoxy groups under acidic conditions can lead to the formation of catechol intermediates, which are more reactive and prone to oxidation. The primary amine allows for easy salt formation with acids (e.g., DOB·HCl), increasing the compound’s shelf life and handling safety. DOB indicates lipophilicity, which facilitates its passage through biological membranes such as the blood–brain barrier.

Synthesis of DOB

The synthesis of 2,5-dimethoxy-4-bromoamphetamine (DOB), CAS Number 64638-07-9, typically begins with 2,5-dimethoxybenzaldehyde as the starting material.

The synthesis commences with 2,5-dimethoxybenzaldehyde. A solution of 2,5-dimethoxybenzaldehyde in glacial acetic acid treated with nitroethane and anhydrous ammonium acetate. This mixture heated on the steam bath. The residue suspended in water and extracted with CHCl₃. Removal of the solvent from extracts yielded a 1-(2,5-dimethoxyphenyl)-2-nitropropene.​

A solution of 1-(2,5-dimethoxyphenyl)-2-nitropropene prepared in anhydrous Et₂O. This solution added slowly to a well-stirred suspension of LAH in anhydrous Et₂O. The mixture brought up to a reflux and maintained there. Finally, added water, followed by the addition of potassium sodium tartrate, and sufficient aqueous NaOH to bring the pH above 9, after evaporate ether to get 2,5-DMA free base.

Synthesis of 2,5-dimethoxyamphetamine from 1-(2,5-dimethoxyphenyl)-2-nitropropene.

To a solution of the free base of 2,5-dimethoxyamphetamine (2,5-DMA) in glacial acetic acid, added elemental bromine dissolved in acetic acid. The cloudy solution washed with Et₂O, made basic with aqueous NaOH, and extracted with CH₂Cl₂. Evaporation of the solvent from the pooled extracts gave a pale amber oil of 2,5-dimethoxy-4-bromoamphetamine, DOB.

The synthetic process requires precision and adherence to strict safety precautions due to the reactivity of intermediates and the pharmacological potency of the final product.

Chemical Reactions of DOB

2,5-Dimethoxy-4-bromoamphetamine (DOB), CAS Number 64638-07-9, functional groups particularly the methoxy substituents and the primary amine allow for several useful transformations.

Salt Formation:

2,5-Dimethoxy-4-bromoamphetamine can be converted to its hydrochloride salt, which is more stable and commonly used. 2,5-Dimethoxy-4-bromoamphetamine dissolved in anhydrous diethyl ether (Et₂O) and saturated with anhydrous HCl gas. In result, white crystals of 2,5-dimethoxy-4-bromoamphetamine hydrochloride (DOB) obtained.

O-Demethylation:

The methoxy groups can be selectively cleaved to yield catechol derivatives. 2,5-Dimethoxy-4-bromoamphetamine reacts with strong Lewis acids like boron tribromide (BBr₃) and aluminum chloride (AlCl₃) to obtain 2-methoxy-5-hydroxy-4-bromoamphetamine.

Applications of DOB

2,5-Dimethoxy-4-bromoamphetamine, DOB, CAS 64638-07-9, has attracted interest in medical research and recreational psychopharmacology due to its potent serotonergic activity and long-lasting psychedelic effects.

1. DOB Medical and Research Applications

DOB has been utilized as a research tool in neuropharmacology, particularly for studying the 5-HT₂A serotonin receptor, which plays a central role in mood, perception, and cognitive processing. Its high binding affinity and selectivity for 5-HT₂A make it a useful ligand for receptor binding studies and structure–activity relationship (SAR) research.

In animal models, DOB is frequently used to provoke the head-twitch response (HTR) – a behavior associated with 5-HT₂A activation – which serves as a proxy for hallucinogenic activity in preclinical research. Additionally, DOB’s resistance to metabolic breakdown and prolonged duration makes it suitable for long-window pharmacokinetic studies compared to shorter-acting compounds like psilocin. Though not approved for clinical use, DOB and its analogs continue to inform the design of non-hallucinogenic 5-HT₂A modulators potentially useful in treating depression or PTSD.

2. DOB Recreational Use

Despite its limited popularity relative to other psychedelics, DOB has seen recreational use in the underground psychedelic scene since the 1970s. First synthesized and described by Alexander Shulgin, DOB was initially distributed in small quantities under the assumption that it was a shorter-acting compound like LSD or mescaline. Users quickly noted its intense visual effects, elevated energy, and extremely long duration—with experiences often lasting 18 to 30 hours.

Recreationally, DOB is typically ingested orally in blotter, liquid, or powder form in dosages ranging from 1 to 3 mg.

The following are oral dosage ranges for pure DOB hydrochloride:

• Threshold: 0.2 mg
• Light: 0.2–0.75 mg
• Common: 0.75–1.75 mg
• Strong: 1.75–2.5 mg
• Heavy: 2.5–3.5 mg
• Overdose: >3.5 mg

Reports from recreational users describe experiences ranging from deeply euphoric and visionary to overstimulating and physically uncomfortable, especially due to vasoconstriction and insomnia.

Light Effects: (plateau between 3 and 6 hours)
An increase in energy, feeling of mental clarity, opening of mental space, less confusing than low doses of LSD, very light visual activity, visual patterns superimposed on vision, enhanced texture perception, shift in colors. Some people find it possible to sleep on low doses of DOB. Body load usually manageable. Nervousness, edginess, some body discomfort, stomach tension, yawning.

Medium Effects: (plateau between 4 and 8 hours)
Increased duration, energizing, pronounced visual effects, marked clarity and reduction of emotions. Some people suggest this might be a good therapeutic tool in cases where excessive emotion might be a problem. Fairly high body load. Muscle and jaw tension, tension headache, eye discomfort, achy back spasms, nausea, general body discomfort.

Strong Effects: (plateau between 6 and 12 hours)
Long duration, visual brightening, able to connect with ideas, heart-opening happiness. These properties, along with its duration, have limited its broader popularity compared to shorter-acting psychedelics.

3. DOB Cultural Significance and Legal Context

DOB holds a place in the history of synthetic psychedelics, particularly within the framework of Shulgin’s work cataloged in PiHKAL: A Chemical Love Story. In the 1990s and early 2000s, DOB appeared sporadically in the global grey market, often mislabeled or distributed as LSD on blotter paper.

Health Effects of DOB Use

2,5-Dimethoxy-4-bromoamphetamine (DOB) CAS 64638-07-9, a potent psychedelic amphetamine, poses significant health risks due to its high pharmacological activity at low doses. Its psychoactive profile demands its acute and chronic effects on human health. DOB’s mechanism of action as a selective serotonin receptor agonist, particularly at the 5-HT₂A receptors, underlies many of its effects on perception, mood, and physiology. As with other serotonergic hallucinogens, exposure to DOB can result in a wide spectrum of physiological and psychological responses depending on the dose, route of exposure, and individual sensitivity.

DOB Acute Effects

The most prominent health effects of DOB occur shortly after exposure and are characterized by intense central nervous system stimulation and altered sensory processing. At active doses DOB can cause visual hallucinations, time dilation, depersonalization, heightened sensory perception, and changes in mood or cognition. Physiologically, acute effects include tachycardia, hypertension, mydriasis, tremors, and increased body temperature. The duration of action is notably long – effects may last 18 to 30 hours, often with an extended come – down phase characterized by fatigue, anxiety, or insomnia.

DOB Chronic and Long-Term Effects

Data on the chronic effects of DOB in humans is limited, largely due to its controlled status and rarity in clinical use. However, long-term concerns mirror those of other serotonergic psychedelics. Repeated high-dose or unregulated use may potentially lead to persistent changes in serotonin signaling, which could affect mood regulation, emotional processing, or cognitive performance. There is limited but growing evidence suggesting that excessive serotonergic stimulation can contribute to hallucinogen persisting perception disorder (HPPD) or exacerbate preexisting psychiatric conditions such as anxiety, bipolar disorder, or schizophrenia.

Additionally, DOB’s structural similarity to amphetamines raises concerns regarding neurotoxicity and cardiovascular strain, especially at higher doses. In animal models, overstimulation of 5-HT receptors has been associated with cortical disruption, receptor downregulation, and stress-related behavior patterns. While not directly addictive, the stimulant properties of DOB may contribute to psychological habituation in susceptible individuals.

DOB Toxicity and Lethality

While DOB is not commonly associated with fatal outcomes at standard doses, cases of overdose have been documented, typically resulting from misidentification or incorrect dosing. The compound’s steep dose-response curve means that slight increases in dose can lead to disproportionately stronger effects and physiological burden. Symptoms of overdose may include hyperthermia, extreme agitation, hallucinosis, severe vasoconstriction, and cardiac arrhythmias. In some reported cases, particularly involving unregulated street formulations, severe vasoconstriction has led to ischemia of extremities, requiring hospitalization or surgical intervention.

There is no specific antidote for DOB poisoning; treatment is supportive and includes benzodiazepines for agitation, cooling measures for hyperthermia, and antihypertensives for elevated blood pressure. Activated charcoal may be used in oral overdose scenarios if administered promptly.

Conclusion

2,5-Dimethoxy-4-bromoamphetamine (DOB), CAS Number 64638-07-9, is a powerful psychedelic compound with strong and long-lasting effects. It acts mainly on the 5-HT₂A serotonin receptor, which is linked to changes in mood, perception, and consciousness. Because of this, DOB is important in scientific research that explores how psychedelic substances affect the brain.

Although DOB is not used in medicine, it is a useful tool in the lab for studying similar compounds and testing how changes in chemical structure affect activity. It has helped researchers examine serotonin-related processes and has influenced the development of new drugs that aim to avoid strong hallucinogenic effects. Due to its strength and long duration, DOB must be handled with great care. DOB also has a place in the history of psychedelics. While it is less known than LSD or psilocybin, it played an important role in early psychedelic chemistry. Today, it remains a valuable substance for research and continues to help scientists learn more about how psychedelic compounds interact with the human brain.

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