Subtopic Deep Dive
Transition State Analysis in Aminolysis Reactions
Research Guide
What is Transition State Analysis in Aminolysis Reactions?
Transition State Analysis in Aminolysis Reactions examines the structures and energies of transition states in nucleophilic acyl substitutions where amines attack esters, carbonates, and related substrates forming tetrahedral intermediates.
Researchers apply linear free energy relationships including Hammett ρ values and Brønsted β coefficients to probe transition state characteristics (Um et al., 2005; 82 citations). Computational methods clarify stepwise mechanisms with defined tetrahedral intermediates (Lee and Sung, 2004; 74 citations). Over 10 key papers from 1977-2016 document kinetics in solvents like acetonitrile and aqueous ethanol (Castro, 2009; 70 citations).
Why It Matters
Transition state analysis guides design of selective acylation reagents by revealing stereoelectronic effects in tetrahedral intermediates (Um et al., 2005). Brønsted βnuc values up to 1.69 indicate late transition states with extensive C-N bond formation, informing catalyst development for organocatalysis (Hoque et al., 2007). Isokinetic relationships from Hammett plots in MeCN differentiate concerted vs. stepwise paths, impacting synthesis of amides from thioesters (Castro, 2009; Lee and Sung, 2004).
Key Research Challenges
Distinguishing Concerted vs Stepwise TS
Large βnuc >1.0 and ρ values suggest late TS but fail to confirm tetrahedral intermediate lifetimes (Hoque et al., 2007; ρnuc=-4.78, βnuc=1.69). Kinetic data alone cannot rule out concerted mechanisms without computational validation (Lee and Sung, 2004). Solvent effects complicate interpretation in MeCN vs. water (Um et al., 2005).
Quantifying Stereoelectronic Effects
Substituent variations yield cross-interaction constants but overlook π-donation in phosphinates (Dey, 2007; βnuc=1.40). Distinguishing field from resonance effects requires multidimensional LFERs not standard in aminolysis studies. Computational TS geometries needed for validation (Adhikary, 2003).
Solvent-Dependent Mechanism Shifts
Aprotic solvents like MeCN enhance nucleophilicity but alter leaving group departure timing (Um et al., 2005). Brønsted plots change slope between aqueous and 44% ethanol media (Castro, 2009). Temperature-dependent isokinetic plots essential but rare (Oh et al., 2001).
Essential Papers
Aminolysis of 2,4‐Dinitrophenyl X‐Substituted Benzoates and Y‐Substituted Phenyl Benzoates in MeCN: Effect of the Reaction Medium on Rate and Mechanism
Ik‐Hwan Um, Sangeun Jeon, Jin‐Ah Seok · 2005 · Chemistry - A European Journal · 82 citations
Abstract Second‐order rate constants ( k N ) have been determined spectrophotometrically for the reactions of 2,4‐dinitrophenyl X‐substituted benzoates ( 1 a – f ) and Y‐substituted phenyl benzoate...
Theoretical and Physical Aspects of Stepwise Mechanisms in Acyl-Transfer Reactions
Ikchoon Lee, Dae Dong Sung · 2004 · Current Organic Chemistry · 74 citations
Recent applications of theoretical and physical approaches to the elucidation of acyl-transfer mechanisms have led to further clarifications of structures of intermediates and transition states inv...
Kinetics and mechanism of the aminolysis of thioesters and thiocarbonates in solution
Enrique A. Castro · 2009 · Pure and Applied Chemistry · 70 citations
Abstract The aminolysis reactions of thioesters and thiocarbonates, in either aqueous solution or in 44 wt % aqueous ethanol at 25 °C, are subjected to a kinetic investigation. The Brønsted-type pl...
Kinetics and Mechanism of the Pyridinolysis of Aryl Phenyl Isothiocyanophosphate in Acetonitrile
Keshab Kumar Adhikary · 2003 · Bulletin of the Korean Chemical Society · 59 citations
The kinetics and mechanism of the pyridinolysis <TEX>$(XC_5H_4N)$</TEX> of Y-aryl phenyl isothiocyanophosphates (1;<TEX>$(YC_6H_4O)\;(C_6H_5O)$</TEX>P(=O)NCS) are investigated in acetonitrile at 55...
New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation
Pavel Nagorny, Zhankui Sun · 2016 · Beilstein Journal of Organic Chemistry · 59 citations
Hydrogen bond donor catalysis represents a rapidly growing subfield of organocatalysis. While traditional hydrogen bond donors containing N–H and O–H moieties have been effectively used for electro...
Kinetics and Mechanism of the Aminolysis of Diphenyl Phosphinic Chloride with Anilines
Md Enamul Hoque, Hai Whang Lee, Hai Lee et al. · 2007 · Bulletin of the Korean Chemical Society · 56 citations
The aminolyses of diphenyl phosphinic chloride (1) with substituted anilines in acetonitrile at 55.0 oC are investigated kinetically. Large Hammett ρ X (ρnuc = ?4.78) and Bronsted β X (βnuc = 1.69)...
Anilinolysis of Diphenyl Thiophosphinic Chloride and Theoretical Studies on Various R<sub>1</sub>R<sub>2</sub>P(O or S)Cl
Nilay Kumar Dey · 2007 · Bulletin of the Korean Chemical Society · 48 citations
The aminolysis of diphenyl thiophosphinic chloride (2) with substituted anilines in acetonitrile at 55.0 oC is investigated kinetically. Kinetic results yield large Hammett ρX (ρnuc = ?3.97) and Br...
Reading Guide
Foundational Papers
Start with Um et al. (2005; 82 citations) for experimental LFERs in ester aminolysis, then Lee and Sung (2004; 74 citations) for computational TS structures in acyl transfers.
Recent Advances
Study Castro (2009; 70 citations) for thioester/thiocarbonate kinetics and Hoque et al. (2007; 56 citations) for phosphinate βnuc extremes indicating late TS.
Core Methods
Brønsted plots (lg kN vs pKa), Hammett ρX/ρZ, cross-interaction constants; DFT optimization of tetrahedral TS geometries.
How PapersFlow Helps You Research Transition State Analysis in Aminolysis Reactions
Discover & Search
Research Agent uses searchPapers with query 'aminolysis tetrahedral intermediate Brønsted βnuc' to retrieve Um et al. (2005; 82 citations), then citationGraph reveals forward citations on solvent effects and findSimilarPapers identifies Castro (2009) kinetics studies. exaSearch semantic search uncovers Lee and Sung (2004) computational validations across 250M+ OpenAlex papers.
Analyze & Verify
Analysis Agent applies readPaperContent to extract Hammett ρ and β values from Um et al. (2005), then verifyResponse with CoVe cross-checks βnuc=1.69 claims against Hoque et al. (2007). runPythonAnalysis fits Brønsted plots from extracted kN vs pKa data using NumPy linear regression, with GRADE scoring kinetic evidence reliability.
Synthesize & Write
Synthesis Agent detects gaps in concerted vs stepwise mechanism coverage across Um (2005) and Lee (2004), flags contradictions in βnuc interpretations. Writing Agent uses latexEditText for reaction schemes, latexSyncCitations to link 10+ papers, latexCompile for publication-ready reviews, and exportMermaid diagrams tetrahedral TS structures.
Use Cases
"Plot Brønsted βnuc values from aminolysis of phosphinic chlorides vs esters"
Research Agent → searchPapers('aminolysis phosphinic Brønsted') → Analysis Agent → readPaperContent(Hoque 2007) + runPythonAnalysis(pandas plot kN vs pKa, β=1.69 fit) → matplotlib figure of βnuc comparison.
"Write LaTeX review of tetrahedral intermediates in ester aminolysis"
Synthesis Agent → gap detection(concerted/stepwise) → Writing Agent → latexEditText(draft mechanisms) → latexSyncCitations(Um 2005, Castro 2009) → latexCompile(PDF with schemes).
"Find code for computational TS optimization in acyl transfer"
Research Agent → paperExtractUrls(Lee 2004) → Code Discovery → paperFindGithubRepo → githubRepoInspect(DFT Gaussian inputs for tetrahedral TS).
Automated Workflows
Deep Research workflow systematically reviews 50+ aminolysis papers: searchPapers → citationGraph(Um 2005 cluster) → structured report with β/ρ tables. DeepScan 7-step analyzes Castro (2009) kinetics with CoVe checkpoints on mechanism claims and runPythonAnalysis for cross-interaction constants. Theorizer generates hypotheses on stereoelectronic TS effects from Hoque (2007) LFER data.
Frequently Asked Questions
What defines transition state analysis in aminolysis?
It uses LFERs like Hammett ρ and Brønsted βnuc to characterize TS structure in amine attacks on esters forming tetrahedral intermediates (Um et al., 2005).
What methods probe aminolysis mechanisms?
Spectrophotometric kN measurements yield βnuc=0.27-1.69; computational geometry optimization confirms stepwise paths (Hoque et al., 2007; Lee and Sung, 2004).
Which are key papers on ester aminolysis TS?
Um et al. (2005; 82 citations) on dinitrophenyl benzoates in MeCN; Castro (2009; 70 citations) on thioesters; Hoque et al. (2007; 56 citations) on phosphinic chlorides.
What open problems exist?
Solvent-independent βnuc calibration; multidimensional LFERs for π-effects; direct tetrahedral intermediate detection beyond kinetics (Dey, 2007; Adhikary, 2003).
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