Kinetic analysis of second order reactions using UV-VIS spectroscopy

A new method was recently developed for the spectroscopic kinetic analysis of reactions with two linearly independent concentration variables. Firstly, the results of this theory applied to experimental data are represented. For this investigation, reactions of the mechanism type A + Bk (1)--> C + D and A + E uc-->|k(2)|F + G were chosen since both reaction steps can be studied separately. The evaluation of the reaction system consisting of both reaction steps gives satisfactory results when the methods of "formal integration" and "singular value decomposition" (SVD) are used. Absorption coefficients of absorbing species are not needed for the evaluation. Only time dependent spectroscopic measuring values and initial concentrations are used in the presented practical example.     

Amination of Bis(trimethylsilyl)-1,2-bisketene with secondary amines: formation of aminodihydrofuranones

The bisketene (Me(3)SiC=C=O)(2) (3) reacts rapidly with 1 equiv of secondary amines to form aminodihydrofuranones 11 as the only observable products. This is in contrast to previous studies (J. Org. Chem. 1999, 64, 4690) of the reactions of 3 with primary amines in which 3 with 1 equiv of amine gives ketenyl amides 4, which slowly cyclize to succinimides 7. The kinetics of the reaction of 3 with morpholine obeyed a rate law with the term [morpholine](2), consistent with rate-limiting formation of the enol amide 14 with catalysis by a second amine molecule. The subsequent formation of 11 is attributed to hindrance of ketonization of intermediate enol amides 14. The furanones 11 react with Me(3)SiOTf to form silyloxyfurans 16, and these react with diethyl diazodicarboxylate, forming maleamide derivatives 17.     

Generation and Trapping of Triafulvene

Substituted methylidenecyclopropanes 12a – d , being easily available from 1,1-dibromo-2-(phenylthio)-cyclopropane ( 9a ), are attractive precursors of triafulvene (2-methylidene-1-cyclopropene; 1 ). Both the sulfoxide 12b and the sulfone 12c react with an excess of alkoxides (t-BuOK and NaOMe) to give 12e and 12f , respectively, while the sulfinyl group of 12b may be replaced by the PhCH₂S substituent in the presence of PhCH₂SH/t-BuOK. These reactions (Scheme 4) may be explained by assuming 1 as a reactive intermediate, although an alternative sequence including carbene 20 (Scheme 6) is not completely ruled out. D -labelling experiments (Scheme 5) do not give conclusive evidence due to D scrambling, but deprotonation/methylation sequences show that H? C(2) of 12a – c is the most acidic proton. Final evidence for 1 results from the reaction of 12d with cyclopentadienide (Scheme 7): the reaction of 1 with cyclopentadiene produces the expected [4 + 2]-cycloaddition product 23 , while some mechanistic insight results from the sequence 12d → 24 → 25 .     

DFT Studies on the addition reaction between germylene and furan

The mechanism of the addition reaction of germylene H₂Ge and furan has been investigated with B3LYP/6-311+G* method, including geometry optimization and vibrational analysis for the involved stationary points on the potential energy surface. From the surface energy profile, it can be predicted that there are four reactions (1)–(4). Reactions (1) and (2) are similar, which are reactions between H₂Ge and C=C of isolated furan. Furthermore, H₂Ge can react with oxygen atom of furan to form a stable complex H₂Ge-Furan. Reactions (3) and (4) are similar, which are reactions between H₂Ge and C=C of the complex H₂Ge-Furan. All the reactions consist of two steps: the two reactants first form an intermediate (INT) through a barrier-free exothermic reaction; this intermediate then isomerizes to a product (P) via a transition state (TS). The article is published in the original.     

Insights into the N‐Heterocyclic Carbene (NHC)‐Catalyzed Intramolecular Cyclization of Aldimines: General Mechanism and Role of Catalyst

One of the most challenging questions in the Lewis base organocatalyst field is how to predict the most electrophilic carbon for the complexation of N‐heterocyclic carbene (NHC) and reactant. This study provides a valuable case for this issue. Multiple mechanisms (A, B, C, D, and E) for the intramolecular cyclization of aldimine catalyzed by NHC were investigated by using density functional theory (DFT). The computed results reveal that the NHC energetically prefers attacking the iminyl carbon (AIC mode, which is associated with mechanisms A and C) rather than attacking the olefin carbon (AOC mode, which is associated with mechanisms B and D) or attacking the carbonyl carbon (ACC mode, which is associated with mechanism E) of aldimine. The calculated results based on the different reaction models indicate that mechanism A (AIC mode), which is associated with the formation of the aza‐Breslow intermediate, is the most favorable pathway. For mechanism A, there are five steps: (1) nucleophilic addition of NHC to the iminyl carbon of aldimine; (2) [1,2]‐proton transfer to form an aza‐Breslow intermediate; (3) intramolecular cyclization; (4) the other [1,2]‐proton transfer; and (5) regeneration of NHC. The analyses of reactivity indexes have been applied to explain the chemoselectivity, and the general principles regarding the possible mechanisms would be useful for the rational design of NHC‐catalyzed chemoselective reactions.     

Coordinatively unsaturated alkyne complexes: synthesis of mono and bis-alkyne complexes of tungsten (II)

[WBr₂(CO₄]_n reacts with alkynes to give complexes [WBr₂CO(RCCR)₂]₂ (1) (R = R′ = Me, Et, Ph; R = Me, R′ = Ph), which react with nucleophiles L{L = CNBu^t, PPh₃, or P(OMe)₃} to give monoalkyne derivatives (WBr₂(CO)(RCCR′)L₂](2). An intermediate bis-alkyne adduct [WBr₂CO(MeCCMe)₂(CNBu^t)] (3) was isolated in the reaction of [WBr₂CO(MeCCMe)₂]₂ with CNBu^t illustrating that cleavage of the dimer (1) is the first stage in these reactions.     

Toward product control in ring‐opening oligomerization of 9H‐9‐borafluorenes

To get deep insights into the structure–reactivity relationship for ring‐opening oligomerization reactions toward targeted design of novel main‐chain boron‐containing materials, detailed DFT B97D/TZVP calculations are carried out to compare the ring‐opening oligomerization of both unsubstituted and tert‐butyl (tBu)‐substituted 9H?9‐borafluorenes. In contrast to substituent exchange between normal boranes, such reactions are initiated by substituent exchanges involving double B? C? B bridged intermediates. On tBu‐substitution, the B? C? B, and B? H? B bridged dimer intermediate is stabilized mainly due to enhanced barrier of 18.1 kcal/mol toward further trimerization channel and higher isomerization barrier of 22.5 kcal/mol toward the double B? H? B bridged dimer. In good agreement with available experiments, it is clearly shown that various product channels can be efficiently controlled by bulky substitution and by reaction temperatures, pointing out the way toward desired higher oligomers with improved thermal stability. © 2014 Wiley Periodicals, Inc.     

Gas-phase reactivity of group 11 dimethylmetallates with allyl iodide

Copper-mediated allylic substitution reactions are widely used in organic synthesis, whereas the analogous reactions for silver and gold are essentially unknown. To unravel why this is the case, the gas-phase reactions of allyl iodide with the coinage metal dimethylmetallates, [CH(3)MCH(3)](-) (M = Cu, Ag and Au), were examined under the near thermal conditions of an ion trap mass spectrometer and via electronic structure calculations. [CH(3)CuCH(3)](-) reacted with allyl iodide with a reaction efficiency of 6.6% of the collision rate to yield: I(-) (75%); the cross-coupling product, [CH(3)CuI](-) (24%); and the homo-coupling product, [C(3)H(5)CuI](-) (1%). [CH(3)AgCH(3)](-) and [CH(3)AuCH(3)](-) reacted substantially slower (reaction efficiencies of 0.028% and 0.072%). [CH(3)AgCH(3)](-) forms I(-) (19%) and [CH(3)AgI](-) (81%), while only I(-) is formed from [CH(3)AuCH(3)](-). Because the experiments do not detect the neutral product(s) formed, which might otherwise help identify the mechanisms of reaction, and to rationalize the observed ionic products and reactivity order, calculations at the B3LYP/def2-QZVP//B3LYP/SDD6-31+G(d) level were conducted on four different mechanisms: (i) S(N)2; (ii) S(N)2'; (iii) oxidative-addition/reductive elimination (OA/RE) via an M(III) η(3)-allyl intermediate; and (iv) OA/RE via an M(III) η(1)-allyl intermediate. For copper, mechanisms (iii) and (iv) are predicted to be competitive. Only the Cu(III) η(3)-allyl intermediate undergoes reductive elimination via two different transition states to yield either the cross-coupling or the homo-coupling products. Their relative barriers are consistent with homo-coupling being a minor pathway. For silver, the kinetically most probable pathway is the S(N)2 reaction, consistent with no homo-coupling product, [C(3)H(5)AgI](-), being observed. For gold, no C-C coupling reaction is kinetically viable. Instead, I(-) is predicted to be formed along with a stable Au(III) η(3)-allyl complex. These results clearly highlight the superiority of organocuprates in allylic substitution reactions.     

Hamiltonian dynamics of chemical reactions. Consecutive first-order reactions and reactions possessing one autocatalytic intermediate

A recently proposed Hamiltonian approach to phenomenological chemical kinetics [T. Georgian and G.L. Findley, Int. J. Quantum Chem., Quantum Biol. Symp. 10 , 331 (1983); T. Georgian, J.M. Halpin, and G.L. Findley, Int. J. Quantum Chem., Quantum Biol. Symp. 11 , 347 (1984)] is applied to all consecutive first-order, single-step reactions, and to all reactions possessing one autocatalytic intermediate. The reaction Hamiltonians presented are shown to be consistent with the phenomenological rate equations and the relationship between reaction form and the form of the reaction potential is discussed. In particular, we show: (1) that the interaction between consecutive reactions manifests itself as a coupling term in the reaction potential, a term which may be eliminated via transition to “normal reaction coordinates” for the chemical system; and (2) that coupled sets of autocatalytic reactions give rise to coupling terms in the reaction Hamiltonian which are characteristic of the reaction mechanism.     

ESR studies on reactions of dicyclopentadienyl dicarbonyl titanium with organic halides

ESR method was used to elucidate the mechanism of the reactions of alkyl, allyl or benzyl halides with dicyclopentadienyldicarbonyl titanium. The paramagnetic [intermediates of the reactions were identified during the course of the reactions. The reaction mechanism based on ESR findings and the products analyses is postulated to operate on radical pathways. When alkyl halides were used to react with the organometallic compound 1, the intermediate found was [Cp₂Ti(CO)X] (C), and the main product was identified to be dicyclopentadienyl-acyl-halo titanium (3), an insertion of TiCO into R-X, i.e. [Cp₂Ti-C(0)R] X. When allyl or benzyl halides were used, the intermediate found was [Cp₂TiX] (B), and the main products were identified to be the dicyclopentadienyl titanium dihalides and the coupling products of allyl or benzyl groups.     

Organoplatinum(IV) tris-chelate complexes, each having a cyclic metallacarbonate ring: synthesis, characterization and kinetic studies of the formation

The complexes [Pt[(CH2)4](NN)], 1a (NN = 2,2'-bipyridine) and 1b (NN = 1,10-phenanthroline) react with 2,3-epoxypropylphenyl ether in the presence of CO2 to give tris-chelate platina(IV)cyclopentane complexes characterized by 1H and 13C NMR spectroscopy as [Pt[(CH2)4](CH2CHCH2OPhOCO2)(NN)], 2. The reactions proceed by the SN2 mechanism and the rates were independent of concentration of CO2. It is demonstrated that for 1a, the reaction proceeds 2.32 times faster than the similar reaction in which the dimethyl analog, [PtMe2(2,2'-bipyridine)], is used. The analog tris-chelate complex [Pt[(CH2)4](CH2CHPhOCO2)(phen)], 3a, was similarly synthesized.     

Insertion, reduction, and carbon-carbon coupling induced by monomeric aluminum hydride compounds bearing substituted pyrrolyl ligands

A monomeric aluminum hydride complex bearing substituted pyrrolyl ligands, AlH[C(4)H(3)N(CH(2)NMe(2))-2](2) (1), was synthesized and structurally characterized. To further confirm the presence of Al--H bonds, the compound AlD[C(4)H(3)N(CH(2)NMe(2))-2](2) ([D]1) was synthesized by reacting LiAlD(4) with [C(4)H(4)N(CH(2)NMe(2))-2]. Compound 1 and [D]1 react with phenyl isothiocyanate yielding Al[C(4)H(3)N(CH(2)NMe(2))-2](2)[eta(3)-SCHNPh] (2) and Al[C(4)H(3)N(CH(2)NMe(2))-2](2)[eta(3)-SCDNPh] ([D]2) by insertion. The reactions of 1 with 9-fluorenone and benzophenone generated the unusual aluminum alkoxide complexes 3 and 4, respectively, through intramolecular proton abstraction and C-C coupling. A mechanistic study shows that 9-fluorenone coordinates to [D]1 and releases one equivalent of HD followed by C-C coupling and hydride transfer to yield the final product. Reduction of benzil with 1 affords aluminum enediolate complex 5 in moderate yield. Mechanistic studies also showed that the benzil was inserted into the aluminum hydride bond of [D]1 through hydroalumination followed by proton transfer to generate the final product [D]5. All new complexes have been characterized by (1)H and (13)C NMR spectroscopy and X-ray crystallography.     

Oxidation of Bromide by Tert‐Butyl Hypochlorite

The kinetics of the oxidation reaction of bromide by tert‐butyl hypochlorite (^tBuOCl) was studied at 25°C, ionic strength 0.5 M, and under isolation conditions. A stopped‐flow spectrophotometer was employed for monitoring the reactions. Kinetic studies show that the reaction is first order with respect to [Br^?] and [^tBuOCl]. Linear dependences of the proton concentration, in perchloric acid medium, and the buffer solution concentration were found on the rate constant. The activation parameters were calculated using the Arrhenius and Eyring equations from the kinetic studies performed to analyze the influence of temperature on the rate constant. The results are consistent with a reaction mechanism of general acid catalysis. The catalytic constants were obtained for the oxidation of bromide by tert‐butyl hypochlorite. The slope obtained for the Brönsted relationship was 0.36.     

A simple method for analysis of consecutive reactions with a second order formation and a first order decay of an intermediate

A simple method is developed to evaluate rate constants from absorbance-time traces for a pair of consecutive reactions consisting of a second order formation and a first order decay of an intermediate. Initially, a first order profile is simulated utilizing the data near the end of the reaction. The difference between this simulated and observed profiles provides the absorbance-time data for the initial phase from which a second order rate constant is evaluated. These rate constants were used to simulate composite kinetic curves which were then compared with experimental curves. This method was used to test the reaction between cis-Pt(NH₃)₂(H₂O)₂ ²⁺ and a nonapeptide, ERFKCPCPT. The reaction proceeds through a cysteine coordinated intermediate formed in a second order process (first order with respect to each reactant). The intermediate is then converted to a product through a first order process, in which both cysteines are coordinated to platinum(II).     

Influence of H2S and thiols on the binding of alkenes and alkynes to ReS4-: the spectator sulfido effect

The three-component reaction of ReS4- (1), H2S, and unsaturated substrates (un = alkene, alkyne) affords the ReV derivatives Re(S)(S2un)(SH)2-. These adducts arise via the addition of H2S to intermediate dithiolates ReS2(S2C2R4)- and dithiolenes ReS2(S2C2R2)-. The species [ReS[S2C2(tms)2](SH)2]-, [ReS(S2C7H10)(SH)2]- (3), and [ReS(S2C2H4)(SH)2]- are prepared according to this route. Similarly, the selenolate-thiolate complex [ReS(S2C7H10)(SeH)(SH)]- (5) is produced by the reaction of [ReS2(S2C7H10)]- with H2Se. The corresponding reactions using benzenethiol in place of H2S afford the more thermally robust adducts [ReS[S2C2(tms)2](SH)(SPh)]-, [ReS(S2C7H10)(SH)(SPh)]- (7), and [ReS(S2C2H4)(SH)(SPh)]-. Norbornanedithiolato compounds 3, 5, and 7 are obtained as pairs of isomers that differ in terms of the relative orientation of the norbornane bridgehead relative to the Re=S unit. The reaction of [ReS(S2C7H10)(SD)2]- (3-d2) with H2S to give 3 is proposed to proceed via elimination of D2S and subsequent addition of H2S. Variable-temperature 1H NMR measurements on the equilibrium of [ReS(S2C6H12)(SPh)(SH)]- with 1,1-hexene, and PhSH gave the following results: deltaH = -7 (+/- 1) kJ x mol(-1); deltaS = 23 (+/- 4) J x mol(-1) x K(-1). Solutions of ethanedithiol and 1 react with C2(tms)2 and C2H4 to give [ReS[S2C2(tms)2](S2C2H4)]- and [ReS(S2C2H4)2]-, respectively, concomitant with loss of H2S. The pathway for the ethanedithiol reaction is examined using 2-mercaptoethanol, affording [ReS[S2C2(tms)2](SC2H4OH)]-, which does not cyclize. Treatment of a solution of diphenylbutadiyne and 1 with PhSH gives two isomers of the dithiolene [ReS(SH)(SPh)[S2C2Ph(C2Ph)]]-. The corresponding reaction of ethanedithiol, diphenylbutadiyne, and 1 affords the 1,4-diphenylbutadiene-1,2,3,4-tetrathiolate complex [[ReS(S2C2H4)]2(S4C4Ph2)]2-.     

Alkylation Reactions at the Benzo Moiety of 2,4‐Dimethoxy‐3‐(phenylsulfonyl)benzo[a]heptalenes – Model Compounds of Colchicinoids

Alkylation reactions of 3‐(X‐sulfonyl)benzo[a]heptalene‐2,4‐diols (X=Ph, morpholin‐4‐yl) and their dimethyl ethers were studied. The diols form with K₂CO₃/MeI in aqueous media the 1‐methylated benzoheptalenes, but in yields not surpassing 20% (Table 1). On the other hand, 2,4‐dimethoxybenzo[a]heptalenes can easily be lithiated at C(3) with BuLi and then treated with alkyl iodides to give the 3‐alkylated forms in good yield (Table 2). Surprising is the reaction with two equiv. or more of t‐BuLi since the alkylation at C(4) is accompanied by the reductive elimination of the X‐sulfonyl group at C(3) (Table 3). Most exciting is also the course of 2,4‐dimethoxy‐3‐(phenylsulfonyl)benzo[a]heptalenes in the presence of an excess of MeLi. After the expected exchange of MeO against Me at C(4) (Scheme 6), rearrangement takes place under formation of 4‐benzyl‐2‐methoxybenzo[a]heptalenes and concomitant loss of the sulfonyl group at C(3) (Table 4). In the case of X=morpholin‐4‐yl, rearrangement cannot occur. However, the intermediate benzyl anions of Type E (Scheme 8) react easily with O₂ of the air to build up corresponding benzo[a]heptalene‐4‐methanols (Table 6).     

Ligands rock & roll: stepwise twisting of two cis-coordinated lopsided N-heterocycles in an octahedral bis(2-phenylazopyridine)-ruthenium(II) complex with seven atropisomers

1H NMR data of alpha-[Ru(azpy)2(MeBim)2](PF6)2 (azpy=2-phenylazopyridine, MeBim=1-methylbenzimidazole), 2, revealed the presence of a total of seven atropisomers at -95 degrees C: three head-to-tail, HT, isomers (A, C, and D), and four head-to-head, HH, isomers which, due to the presence of an intrinsic C2 axis in the alpha-[Ru(azpy)2] moiety, are two sets of identical pairs (B/B and E/E). The NMR data of 2 represent a unique example of a coordination compound that shows a variable temperature (VT) behavior with more, well-defined steps of slow-to-fast exchange of its atropisomers. At 65 degrees C, all atropisomers are in fast exchange; on lowering the temperature the sharp signals first broaden (at room temperature) and consecutively split up into two sets of relatively sharp signals, in slow exchange, at about 0 degrees C (D, 40 %, and the coalesced signals of ABBCEE, 60 %). Upon further cooling, the set of peaks belonging to D remain sharp until the lowest recording temperatures. The signals of the other set of resonances, on the other hand, first broaden again and then separate into two sets of broad peaks (C/E/E and A) and one set of sharp peaks (B and B in fast exchange); on lowering the temperature even more, these signals broaden once again and finally, at -95 degrees C, are split up into a total of four sets of signal (A, B/B, C, and E/E). At low temperatures, ROESY experiments revealed that atropisomerization occurs through the synchronous rotation of both MeBim ligands in the interconversion of the two "identical" HH atropisomers B and B, as well as in the interconversion between C and E/E. The HH rotamers B/B furthermore exhibit a slow-to-fast exchange atropisomerization behavior that is observed independently from the other dynamic processes in this compound. The versatile cis bifunctional binding of the DNA model bases (MeBim ligands) in 2 parallels the observation of alpha-[Ru(azpy)2Cl2] which shows extraordinarly high cytotoxicity against tumor cell lines.     

Stereoselective total syntheses of three Lycopodium alkaloids, (-)-magellanine, (+)-magellaninone, and (+)-paniculatine, based on two Pauson-Khand reactions

The total syntheses of (-)-magellanine, (+)-magellaninone, and (+)-paniculatine were completed from diethyl l-tartrate via the common intermediate in a stereoselective manner. The crucial steps in these syntheses involved two intramolecular Pauson-Khand reactions of enynes: the first Pauson-Khand reaction constructed the bicyclo[4.3.0] carbon framework, the corresponding A and B rings of these alkaloids in a highly stereoselective manner, whereas the second Pauson-Khand reaction stereoselectively produced the bicyclo[3.3.0]skeleton, which could be converted into the C and D rings of the target natural products.     

Mechanistic Study on the Cleavage and Reorganization of C(sp3)?H and CN Bonds in Carbodiimides: Synthesis of 1,2‐Dihydrothiopyrimidines and 2,3‐Dihydropyrimidinthiones through Four‐Component Coupling

This study sheds light on the cleavage and reorganization of C(sp³)? H and C?N bonds of carbodiimides in a three‐component reaction of terminal alkynes, sulfur, and carbodiimides by a combination of methods including 1) isolation and X‐ray analysis of six‐membered‐ring lithium species 2‐S , 2) trapping of the oxygen‐analogues ( B‐O and D‐O ) of both four‐membered‐ring intermediate B‐S and ring‐opening intermediate D‐S , 3) deuterium labeling studies, and 4) theoretical studies. These results show that 1) the reaction rate‐determining step is [2+2] cycloaddition, 2) the C?N bond cleavage takes place before C(sp³)? H bond cleavage, 3) the hydrogen attached to C6 in 2‐S originates from the carbodiimide, and 4) three types of new aza‐heterocycles, such as 1,2‐dihydrothiopyrimidines, N‐acyl 2,3‐dihydropyrimidinthiones, and 1,2‐dihydropyrimidinamino acids are constructed efficiently based on 2‐S . All results strongly support the idea that the reaction proceeds through [2+2] cycloaddition/4π electrocyclic ring‐opening/1,5‐H shift/6π electrocyclic ring‐closing as key steps. The research strategy on the synthesis, isolation, and reactivity investigation of important intermediates in metal‐mediated reactions not only helps achieve an in‐depth understanding of reaction mechanisms but also leads to the discovery of new synthetically useful reactions based on the important intermediates.     

Amidomethylation of indoles and cyclisations to spiro[pyrrolo[4,3,2-de]isoquinoline-3,4′-piperidines]

4-Aminomethylindoles react with aldehydes and ketones to form pyrrolo[4,3,2-de]isoquinolines. The structures of starting materials and end products were determined using 1D and 2D ¹H nmr techniques.