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Abstract
1-Naphthoylchloride, featuring the functional group −C(=O)Cl, is a key component in numerous organic syntheses and plays a crucial role in the synthesis of JWH derivatives. This comprehensive article provides an extensive overview of 1-naphthoylchloride, covering its general information, physico-chemical properties, detailed chemical information, synthesis methods, insightful conclusions, and a comprehensive bibliography.
General Information About 1-naphthoylchloride [1-7]
Other synonyms names of 1-naphthoylchloride are: 1-(Chlorocarbonyl)naphthalene; 1-Naphthalenecarbonyl chloride; 1-naphthalenecarboxylic acid chloride; 1-naphthaloylchloride; 1-Naphthoic acid chloride; 1-naphthylcarbonyl chloride; alpha-Naphthoyl chloride
IUPAC Name of 1-naphthoylchloride: naphthalene-1-carbonyl chloride
CAS number is 879-18-5
Physico-Chemical Properties of 1-naphthoylchloride [1-7]
- Molecular Formula C11H7ClO
- Molar Weight 190.62 g/mol
- 118 °C / 0.1 mm (436.75 °C / 760 mmHg) Alfa Aesar
- 120 °C / 2 mmHg (335.9846 °C / 760 mmHg) Manchester Organics
- 190 °C / 35 mmHg OU Chemical Safety Data
- 118 °C / 0.1 mm (436.75 °C / 760 mmHg) Alfa Aesar
- 190 °C / 35 mmHg (322.1218 °C / 760 mmHg) Sigma-Aldrich
- 120 °C / 2 mm (335.9846 °C / 760 mmHg) Oakwood
- 16-19 °C Alfa Aesar
- 16-19 °C Manchester Organics
- 26 °C OU Chemical Safety Data
- 18 °C Jean-Claude Bradley
- 26 °C Jean-Claude Bradley
- 16-19 °C Alfa Aesar
- 16-19 °C Sigma-Aldrich
- 16-19 °C Oakwood
- Refraction index 1.6525 Alfa Aesar and 1.652 Sigma-Aldrich
- Density 1.265 g/mL Alfa Aesar and 1.265 g/mL Sigma-Aldrich
- Solubility: decomposes in water
- Color/Form: White, Liquid or Solid
- Safety and Handling: Danger!; Serious eye damage/eye irritation Category 1; Skin corrosion/irritation Category 1B; H318-Causes serious eye damage; H314-Causes severe skin burns and eye damage; Toxic Gases and Vapors, Acid Halides.
Structural formula present on Figure 1.
Figure 1. Structure of 1-naphthoylchloride
Liquid possible of the 1-naphthoylchloride can be seen in the picture provided in Figure 2.
Figure 2. Liquid of 1-naphthoylchloride
Chemical Information of 1-naphthoylchloride [1-8]
In the field of organic chemistry, an acyl chloride, also known as an acid chloride, refers to an organic compound that contains the functional group −C(=O)Cl. Its chemical formula is typically represented as R−COCl, where R represents a side chain. These compounds are considered reactive derivatives of carboxylic acids (R−C(=O)OH). Acyl chlorides constitute a significant subgroup within the category of acyl halides. Due to their inability to form hydrogen bonds, they exhibit lower boiling and melting points compared to similar carboxylic acids. Acyl chlorides with low molecular weight are often lachrymators, and they exhibit violent reactions when exposed to water, alcohols, and amines.
1-Naphthoyl chloride is a metabolite derived from 1-naphthol. It has found applications in the synthesis of steroidal alkaloids, including the anti-inflammatory drug indomethacin and the anesthetic ketamine. Moreover, 1-Naphthoyl chloride serves as a precursor in the production of synthetic cannabinoids, which are substances that mimic the effects of cannabis but are not derived from marijuana. These synthetic cannabinoids interact with receptors present on specific cells that are sensitive to cannabinoids. This binding leads to alterations in cellular function and can induce psychological effects such as paranoia and hallucinations.
Reactions involving 1-naphthoyl chloride:
When exposed to water, acyl chlorides undergo hydrolysis, resulting in the formation of the corresponding carboxylic acid and hydrochloric acid. Figure 3.
When alcohols react with 1-naphthoyl chloride, the presence of bases, such as pyridine or N,N-dimethylformamide, serves as a catalyst for acylation. These reagents activate the acyl chloride through a mechanism known as nucleophilic catalysis. In this process, the amine acts as a nucleophile, attacking the carbonyl bond. Initially, a transient tetrahedral intermediate is formed, which is then converted into a quaternary acylammonium salt through the displacement of the leaving group. This quaternary acylammonium salt is more susceptible to attack by alcohols or other nucleophiles. Figure 4.
The reaction of 1-naphthoyl chloride with thiols involves the substitution of the chlorine atom with a thiol group. This reaction can be facilitated by the presence of a base, such as sodium hydroxide or triethylamine, which acts as a catalyst. The thiol attacks the carbonyl carbon of the acyl chloride, leading to the formation of a tetrahedral intermediate. The intermediate then undergoes elimination of the chloride ion, resulting in the incorporation of the thiol group into the acyl chloride molecule. This reaction is an important step in the synthesis of thioesters and other sulfur-containing compounds. The resulting product can be further utilized in various chemical transformations and organic synthesis processes. Figure 5.
Figure 5. Reaction with Thiols
The reaction of 1-naphthoyl chloride with ammonia, primary, and secondary amines results in the production of their respective amides. To facilitate the reaction and eliminate the by-product, hydrochloric acid, it is beneficial to employ an alkaline solution, pyridine, or an excess of the amine. These substances act as catalysts, promoting the conversion of the acyl chloride to the desired amide compound. By utilizing these reaction conditions, the formation of amides can be achieved more efficiently and with improved yields. Figure 6.
When 1-naphthoyl chloride reacts with carboxylic acid salts, it undergoes a transformation, leading to the formation of carboxylic acid anhydrides. Figure 7.
1-naphthoyl chloride reacts with cyanides. Figure 8.
Figure 8. Reaction with cyanides.
Reactions with Gilman reagents result in the formation of ketones, while reactions with Grignard reagents yield alcohols. Carbon nucleophiles, such as Grignard reagents, convert acyl chlorides into ketones. These ketones can then undergo further reaction with a second equivalent of the nucleophile to produce tertiary alcohols. In the case of acyl halides reacting with certain organocadmium reagents, the reaction stops at the ketone stage. Similarly, the reaction with Gilman reagents also leads to the formation of ketones, as these lithium diorganocopper compounds exhibit lower nucleophilicity. Figure 9.
Figure 9. Reactions with Grignard and Gilman reagents
Chloroanhydrides are reduced by strong reducing agents such as LiAlH4 or DIBAL-H to form primary alcohols. Figure 10.
Figure 10. Reduced by strong reducing agents such as LiAlH4 or DIBAL-H
Lithium tri-tert-butoxyaluminum hydride (LiAlH(Ot-Bu)3), a bulky reducing agent, reduces 1-naphthoyl chloride to an aldehyde. Figure 11.
Figure 11. Reduced by LiAlH(Ot-Bu)3
Chloroanhydrides of carboxylic acids, in the presence of Lewis acids such as iron(III) chloride or aluminum chloride, undergo Friedel-Crafts reaction with aromatic compounds, resulting in the formation of aromatic ketones. Figure 12.
Figure 12. Friedel-Crafts reaction
Acyl chlorides undergo reactions with low-valent metal centers to form transition metal acyl complexes. One example is the potential oxidative addition of 1-Naphthoylchloride to Vaska’s complex, which converts square planar Ir(I) to octahedral Ir(III). This reaction illustrates the transformation of the coordination geometry and oxidation state of the metal center. Figure 13.
Figure 13. Reaction by Vaska’s complex
The synthesis reaction of naphthoylindole, which is also employed in the synthesis of JWH derivatives. Figure 14.
Figure 14. Reaction with indole
Synthesis of 1-naphthoylchloride [9, 10]
In laboratory settings, acyl chlorides are typically synthesized by treating carboxylic acids with thionyl chloride (SOCl2). This reaction is catalyzed by dimethylformamide (DMF) and other additives. Thionyl chloride is an ideal reagent for this purpose due to the gaseous nature of its by-products (HCl, SO2) and its low boiling point (76 °C), allowing easy removal of residual thionyl chloride. The catalytic role of DMF involves its reaction with oxalyl chloride to generate the Vilsmeier reagent, an iminium intermediate. This intermediate then reacts with the carboxylic acid, forming a mixed imino-anhydride. Through acyl substitution with the liberated chloride, the acid anhydride is formed, accompanied by the release of regenerated DMF. Oxalyl chloride, although more expensive than thionyl chloride, is a milder reagent, offering greater selectivity. The synthesis process follows the scheme depicted in Figure 15.
Figure 15. General scheme of 1-naphthoylchloride synthesis
Making thionyl chloride
Conclusion
1-Naphthoyl chloride is a typical representative of acyl chlorides. It serves as a metabolite of 1-naphthol and finds application in various synthesis processes. Notably, it has been utilized in the synthesis of steroidal alkaloids, including well-known pharmaceuticals such as the anti-inflammatory drug indomethacin and the anesthetic ketamine. Furthermore, 1-naphthoyl chloride plays a crucial role in the synthesis of derivatives of JWH, which are compounds of interest due to their potential pharmacological properties. Its versatile reactivity and wide range of applications make 1-naphthoyl chloride a valuable compound in organic synthesis.
Bibliography
- https://materials.springer.com/substanceprofile/docs/smsid_ybxmowrnpdxkkvxe
- https://pubchem.ncbi.nlm.nih.gov/compound/1-Naphthoyl-chloride
- https://en.wikipedia.org/wiki/Acyl_chloride
- https://www.chemspider.com/Chemical-Structure.63334.html?rid=86ad3adf-4675-4cba-854b-dc9f8f4d6bb3
- https://www.sigmaaldrich.com/UA/en/product/aldrich/250252
- https://www.fishersci.co.uk/shop/products/1-naphthoyl-chloride-99-thermo-scientific/10409950
- https://en.wikipedia.org/wiki/Vaska%27s_complex
- Hartwig, John (2010). Organotransition Metal Chemistry: From Bonding to Catalysis. New York: University Science Books. p. 1160. ISBN 978-1-938787-15-7. https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201004890
- Martin Ansell (1972). “Preparation of acyl halides”. In Saul Patai (ed.). Acyl Halides. PATAI’S Chemistry of Functional Groups. pp. 35–68. doi:10.1002/9780470771273.ch2 https://onlinelibrary.wiley.com/doi/10.1002/9780470771273.ch2
- Giovanni Appendino, Alberto Minassia, Orazio Taglialatela-Scafati Recreational drug discovery: natural products as lead structures for the synthesis of smart drugs. Nat. Prod. Rep., 2014, 31, pp. 880-904. DOI: 10.1039/c4np00010b https://pubs.rsc.org/en/content/articlelanding/2014/NP/c4np00010b