SITE-SPECIFIC PROTEIN MODIFICATION WITH 5-BROMOVALERIC ACID DERIVATIVES

Site-Specific Protein Modification with 5-Bromovaleric Acid Derivatives

Site-Specific Protein Modification with 5-Bromovaleric Acid Derivatives

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5-Bromovaleric Acid: A Powerful Bifunctional Intermediate in Organic Chemistry



 Introduction


In synthetic chemistry, versatility is key. Some molecules offer just one reactive group, limiting their utility. But others, like 5-Bromovaleric Acid, provide two reactive sites—unlocking a range of possible transformations. With a terminal bromine atom and a carboxylic acid group, 5-Bromovaleric Acid is a valuable building block used in pharmaceutical synthesis, bioactive compound design, and polymer science.


This article dives into the structure, properties, and practical applications of 5-Bromovaleric Acid—along with a hands-on synthetic example to show how it’s used in the lab.






 Chemical Identity




  • IUPAC Name: 5-Bromopentanoic acid




  • Common Name: 5-Bromovaleric acid




  • Molecular Formula: C₅H₉BrO₂




  • Molecular Weight: 181.03 g/mol




  • Structure:




    Br–CH₂–CH₂–CH₂–CH₂–COOH



This compound features:





  • A carboxylic acid (–COOH) group: acid, polar, reactive in esterification and amidation




  • A bromine atom on the ω-carbon: a good leaving group, ideal for nucleophilic substitution (SN2)







 Physical and Chemical Properties

































Property Value
Appearance White crystalline solid
Melting Point 32–35°C
Solubility (Water) Moderately soluble
Solubility (Organic) Soluble in ethanol, DMSO, acetone
Reactivity Highly reactive at Br and COOH




The combination of acidic and electrophilic functionality gives it broad utility in multistep synthesis.






 Reactivity Overview


1. Carboxylic Acid Group:




  • Esterification: Reacts with alcohols in acid




  • Amide formation: With amines using coupling agents (EDC, DCC)




  • Conversion to acid chloride: With SOCl₂ or oxalyl chloride




2. Bromine Substitution (SN2):




  • Replaces Br with nucleophiles:





    • NH₃ / Amines → 5-Aminovaleric acid




    • NaN₃ → 5-Azidovaleric acid




    • NaCN → 5-Cyanovaleric acid




    • RS⁻ → Thiol derivatives




    • Mg → Grignard reagent for C–C bond formation









 Example: Synthesis of 5-Aminovaleric Acid from 5-Bromovaleric Acid


Let’s walk through a simple real-world transformation:



 Objective:


Convert 5-Bromovaleric Acid to 5-Aminovaleric Acid (a γ-amino acid useful in peptide mimics and polymer precursors).



 Reaction Scheme:



Br–(CH2)4–COOH + NH3 → H2N–(CH2)4–COOH + HBr


 Procedure (Laboratory Scale):




  1. Reagents:





    • 5-Bromovaleric acid (1.0 g, 5.5 mmol)




    • Ammonia (aqueous, excess or gas bubbled in)




    • Solvent: Ethanol/water mixture or neat aqueous ammonia




    • Stirring at room temp or mild heat (40–60°C)






  2. Reaction Time:





    • 12–24 hours depending on concentration and temperature






  3. Work-Up:





    • Remove excess ammonia under reduced pressure




    • Adjust pH to ~2–3 with HCl to protonate amine




    • Extract into water; purify by crystallization or ion-exchange






  4. Product:





    • 5-Aminovaleric acid (H₂N–(CH₂)₄–COOH), a white solid






 Notes:




  • This is a clean SN2 reaction where bromide is the leaving group, and ammonia acts as the nucleophile.




  • The reaction avoids racemization since all carbons are achiral.







 Applications


1. Pharmaceutical Development




  • Used in making GABA analogs and neuroactive agents




  • Functions as a chain linker in peptide and drug design




  • Precursor to δ-valerolactam, a ring used in CNS drugs




2. Polymer Science




  • Reacts to form nylon-like polyamides




  • Used to create bioerodible materials and hydrogels




3. Bioconjugation




  • After functionalization, can be linked to:





    • Peptides




    • Polymers




    • Nanoparticles









 Safety and Handling


While not highly toxic, 5-Bromovaleric Acid should be handled with standard lab precautions:


























Hazard Description
Skin/Eye Irritant Can cause irritation on contact
Toxic if Inhaled Avoid breathing dust or vapors
Decomposition May release HBr if overheated




Safe Handling:




  • Wear gloves, goggles, lab coat




  • Use in fume hood




  • Store in cool, dry, airtight container







 Analytical Identification





























Method What It Shows
¹H NMR Br–CH₂ (downfield ~3.4 ppm), CH₂ chain, COOH singlet
IR Strong C=O stretch (~1700 cm⁻¹), broad O–H (2500–3000)
GC-MS Molecular ion at 181 m/z; isotopic Br pattern
HPLC High-resolution purity check







 Summary





























Feature Details
Dual Reactivity Bromine (electrophilic) and COOH (acidic)
Main Use Intermediate in fine chemical synthesis
Key Reactions SN2, esterification, amidation, lactam formation
Example Product 5-Aminovaleric Acid







Final Thoughts


5-Bromovaleric Acid is a compact yet powerful intermediate for both lab-scale and industrial applications. Its ability to link, transform, and diversify molecules makes it essential in drug synthesis, polymer design, and bioconjugation strategies.


Whether you’re making bioactive amines, click chemistry precursors, or functional polymers, this compound offers a reliable, flexible pathway to molecular innovation.

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