{"doi":"10.1002/poc.1564","title":"A remarkable difference in the deprotonation steps of the Friedel–Crafts acylation and alkylation reactions","abstract":"<jats:title>Abstract</jats:title><jats:p>Friedel–Crafts acylation and alkylation reactions were investigated using density functional theory calculations. The reaction systems studied were (benzene + acetyl chloride + Al<jats:sub>2</jats:sub>Cl<jats:sub>6</jats:sub> (or AlCl<jats:sub>3</jats:sub>)) and (benzene + 2‐chloropropane + Al<jats:sub>2</jats:sub>Cl<jats:sub>6</jats:sub>). In the acylation reaction, the acylium ion intermediate is reached either via a MeC(Cl)OAl<jats:sub>2</jats:sub>Cl<jats:sub>6</jats:sub> complex or via direct Cl transfer: MeC(O)ClAl<jats:sub>2</jats:sub>Cl<jats:sub>6</jats:sub> → MeCO<jats:sup>⌉+</jats:sup>Al<jats:sub>2</jats:sub>Cl<jats:inline-graphic xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"graphic/tex2gif-stack-1.gif\" xlink:title=\"urn:x-wiley:08943230:media:POC1564:tex2gif-stack-1\"/>. The ion adds to benzene electrophilically to form a Wheland intermediate containing a strong CHCl hydrogen bond, which leads to deprotonation and the subsequent formation of acetophenone. The resulting HClAl<jats:sub>2</jats:sub>Cl<jats:sub>6</jats:sub> fragment is subjected to a nucleophilic attack by the carbonyl oxygen of the acetophenone, and recovery of the Al<jats:sub>2</jats:sub>Cl<jats:sub>6</jats:sub> bridge is unlikely. Attack of the Al<jats:sub>2</jats:sub>Cl<jats:sub>6</jats:sub> moiety by MeC(Cl)O gives the complex MeC(Cl)O–AlCl<jats:sub>3</jats:sub>, whose reactivity toward acylation is similar to that of the MeC(Cl)O–Al<jats:sub>2</jats:sub>Cl<jats:sub>6</jats:sub> complex. In the alkylation reaction, deprotonation does not take place, but rather a [1,2] H‐shift from the Wheland intermediate. The resulting <jats:italic>α</jats:italic>‐protonated cumene undergoes deprotonation, with subsequent recovery of the Al<jats:sub>2</jats:sub>Cl<jats:sub>6</jats:sub> bridge. In addition, the Al<jats:sub>2</jats:sub>Cl<jats:sub>6</jats:sub>‐catalyzed isomerization of the <jats:italic>n</jats:italic>‐propyl to the isopropyl cation was found to be a dyotropic shift. Copyright © 2009 John Wiley &amp; Sons, Ltd.</jats:p>","journal":"Journal of Physical Organic Chemistry","year":2009,"id":42573,"datarank":1.258126928026088,"base_score":3.295836866004329,"endowment":3.295836866004329,"self_citation_contribution":0.4943755299006494,"citation_network_contribution":0.7637513981254387,"self_endowment_contribution":0.4943755299006494,"citer_contribution":0.7637513981254387,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":26,"citers_with_citation_signal":22,"citers_with_endowment":22,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":203605,"name":"Shoko Yamazaki","orcid":null,"position":1,"is_corresponding":false},{"id":203604,"name":"Shinichi Yamabe","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.295836866004329,"endowment":3.295836866004329,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18998881","pmcid":null,"openalex_id":"https://openalex.org/W2084996602","authors":[],"funders":[],"total_grants":0,"fwci":0.5111,"citation_percentile":0.67191011,"influential_citations":1,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":2},{"year":2014,"count":1},{"year":2015,"count":3},{"year":2017,"count":1},{"year":2019,"count":2},{"year":2020,"count":3},{"year":2021,"count":4},{"year":2022,"count":1},{"year":2024,"count":4},{"year":2025,"count":2}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/poc.1564","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/poc.1564","host_type":"BRONZE"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/poc.1564","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fpoc.1564","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/poc.1564","host_type":"publisher"},{"url":"https://doi.org/10.1002/poc.1564","host_type":"journal"}],"fields_of_study":["Chemical Reaction Mechanisms","Ammonia Synthesis and Nitrogen Reduction","Organic and Inorganic Chemical Reactions","Chemistry"],"mesh_terms":[],"keywords":["Chemistry","Deprotonation","Medicinal chemistry","Alkylation","Protonation","Acetophenone","Acylation","Reactivity (psychology)","Friedel–Crafts reaction","Isomerization","Nucleophile","Photochemistry","Organic chemistry","Catalysis","Ion"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-14T03:46:35.290278Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}