Crossover experiment

Hthiated 4-substituted-2-methylthia2oles (171) at -78 C (Scheme 80). Crossover experiments at—78 and 25°C using thiazoles bearing different substituents (R = Me, Ph) proved that at low temperature the lithioderivatives (172 and 173) do not exchange H/Li and that the product ratios (175/176) observed are the result of independent metala-tion of the 2-methyl and the C-5 positions in a kinetically controlled process (444). At elevated temperatures the thermodynamic acidities prevail and the resonance stabilized benzyl-type anion (Scheme 81) becomes more abundant, so that in fine the kinetic lithio derivative is 173, whereas the thermodynamic derivative is 172. 

The intramolecular nature of the rearrangement was firmly established by a crossover experiment in which 39 and 40 were heated simultaneously and found to yield the same products as when they were heated separately. There was no evidence for the formation of... 

Rapid exchange of positions was observed for acyl and amidoyl groups in the NMR spectra of compounds 36 in 1-chloronaphthalene solution at high temperatures (170-215°C) (Scheme 18). [72JCS(CC)709]. Crossover experiments clearly indicated the intermolecular exchange. The value of the free-energy barrier was determined as AG = 100 kJ mol at the coales-... 

JCS(P1)2673 89H1121]. As proven by crossover experiments, interconversion of the tautomers occurs intermolecularly, an ion pair 37c being the intermediate in the dissociation-recombination mechanism of the rearrangement. 

The rearranged dicationic species 4, which has been shown to be an intermediate, leads to the stable benzidine 2 upon deprotonation. It has been demonstrated by crossover experiments that the rearrangement does not proceed via a dissoci-ation/recombination process. From the reaction of hydrazobenzene the benzidine is obtained as the major product (up to 70% yield), together with products from side reactions—2,4 -diaminobiphenyl 5 (up to 30% yield) and small amounts of 2,2 -diaminobiphenyl 6 as well as o- and /j-semidine 7 and 8 ... 

An arenediazonium ion 1 in aqueous alkaline solution is in equilibrium with the corresponding diazohydroxide 4 The latter can upon deprotonation react with diazonium ion 1, to give the so-called anhydride 5. An intermediate product 5 can decompose to a phenyl radical 6 and the phenyldiazoxy radical 7, and molecular nitrogen. Evidence for an intermediate diazoanhydride 5 came from crossover experiments " ... 

Another helpful test is the so-called crossover experiment. Thus, a mixture of di-Pd(CH3) (PR3)2 and cA-Pd(CD3)2(PR.3)2 yields only C2D6 and C2H6 C2H3D3 is absent.20 This result shows that the elimination reaction is intramolecular. 

Competition reactions ad eosdem, 106 ad eundem, 105 (See also Reactions, trapping) Competitive inhibitor, 92 Complexation equilibria, 145-148 Composite rate constants, 161-164 Concentration-jump method, 52-55 Concurrent reactions, 58-64 Consecutive reactions, 70, 130 Continuous-flow method, 254—255 Control factor, 85 Crossover experiment, 112... 

The exact mechanism has still not been completely worked out. Opinions have been expressed that it is completely intermolecular, completely intramolecular, and partially inter- and intramolecular. " One way to decide between inter- and intramolecular processes is to run the reaction of the phenolic ester in the presence of another aromatic compound, say, toluene. If some of the toluene is acylated, the reaction must be, at least in part, interraolecular. If the toluene is not acylated, the presumption is that the reaction is intramolecular, though this is not certain, for it may be that the toluene is not attacked because it is less active than the other. A number of such experiments (called crossover experiments) have been carried out sometimes crossover products have been found and sometimes not. As in 11-14, an initial complex (40) is formed between the substrate and the catalyst, so that a catalyst/substrate molar ratio of at least 1 1 is required. 

For example, crossover experiments have demonstrated that the ZnCl2-catalyzed reaction is intermolecular Yagodin, V.G. Bunina-Krivorukova, L.I. Bal yan, Kh.V. J. Org. Chem. USSR, 1971, 7, 1491. 

Further evidence consistent with the polar radical pair mechanism was provided by a crossover experiment (Scheme 6.26). A 1 1 mixture of labeled 8Z /8 and unlabeled 8Z/8E was heated in xylene at 125 °C for 2h and at 135 °C for 4h to afford hydroxypyrimidinones 3 and 3. Analysis of the products by high resolution mass spectrometry showed no crossover between the labeled and unlabeled fragments. This result reinforces the computational results discussed previously wherein PRP recombines to give product within the solvent cage (Scheme 6.24). 

This accounts for the considerable discrepancy between the alkene Z/E ratio found on work-up and the initial oxaphosphetan ais/trans ratio. By approaching the problem from the starting point of the diastereomeric phosphonium salts (19) and (20), deprotonation studies and crossover experiments showed that the retro-Wittig reaction was only detectable with the erythreo isomer (19) via the cis-oxaphosphetan (17). Furthermore, it was shown that under lithium-salt-free conditions, mixtures of (19) and (20) exhibited stereochemical drift because of a synergistic effect (of undefined mechanism) between the oxaphosphetans (17) and (18) during their decomposition to alkenes. 

In order to further examine the role of a pinacolic intermediate, a crossover experiment wa conducted. In the reaction of a lsl mixture of TBP and benzopinacol with U, a statistical distribution of all 6 coupled products was seen. This surprising result shows that the carbon-carbon bond of the pinacol is broken before the products are formed. 

Cyclohexadienylidenes, disubstituted at the 4-position are expected to be kinetically more stable than the parent carbene, however, the rearrangement to benzene derivatives is still very exothermic. The gas phase chemistry of 4,4-dimethyl-2,5-cyclohexadienylidene Is was investigated by Jones et al.100,101 The gas phase pyrolysis of the diazo compound 2s produces a mixture of p-xylene and toluene, and by crossover experiments it was demonstrated that the methyl group transfer occurs intermolecularly via free radicals. Thus, the pyrolysis of a mixture of the dimethyl and the diethyl derivative 2s and 2t... 

A simple and straightforward way to distinguish between a direct insertion process and one going through free radicals is by a crossover experiment. 

Cyclohexane and cyclohexane-d12 have been used as the probe for crossover and, hence, the reactive multiplicity of the subject carbenes. By combining direct and triplet-sensitized generation of the carbene with kinetic analysis from laser spectroscopy and the results of the crossover experiments, a rather complete picture of the reaction of aromatic carbenes with hydrocarbons emerges. 

Xanthylidene does not react measurably with cyclohexane at room temperature (Table 5). Thermolysis of DAX at high temperature does, however, give some of the expected coupling product 9-cyclohexylxanthene. The crossover experiment (1 1 C6H12, C6D12) reveals that this product is not formed by the abstraction-recombination sequence. This observation is consistent with the direct insertion characteristic of a singlet carbene. 

C-C bond formation mediated by silane.6,6a 6f With respect to the development of intramolecular variants, these seminal studies lay fallow until 1990, at which point the palladium- and nickel-catalyzed reductive cyclization of tethered 1,3-dienes mediated by silane was disclosed. As demonstrated by the hydrosilylation-cyclization of 1,3,8,10-tetraene 21a, the /rarcr-divinylcyclopentanes 21b and 21c are produced in excellent yield, but with modest stereoselectivity.46 Bu3SnH was shown to participate in an analogous cyclization.46 Isotopic labeling and crossover experiments provide evidence against a mechanism involving initial diene hydrosilylation. Rather, the collective data corroborate a mechanism involving oxidative coupling of the diene followed by silane activation (Scheme 15). 

Aldehyde 54 and the hydroxamic acids 55 were generated together in an acid-catalysed elimination reaction (Scheme 7 pathway (ii)). A crossover experiment indicated that esters are formed in a concerted rearrangement concomitant with the likely formation of the hydroxynitrene 57 (Scheme 7 pathway (iii)) while there is no evidence to date for the formation of hydroxynitrene, joint solvolysis of equimolar quantities of /V-acetoxy-/V-butoxy-/>-chlorobenzamide 26e and N- acetoxy-/V-benzyloxybenzamide 27a afforded significant quantities of butyl p-chlorobenzo-ate (36%) and benzyl benzoate (54%) as the only esters. This is an example of a HERON reaction, which has been identified in these laboratories as a characteristic rearrangement of bisheteroatom-substituted amides.32,33,42 43 155 158 Since ester formation was shown to prevail in neutral or low acid concentrations, it could involve the conjugate anion of the hydroxamic acid (vide infra).158... 

Initially, a reaction of A-acetoxy-A-butoxybenzamide 25c with A-methyl aniline 61 in butyl benzoate 63(R = Bu) and acetic acid. Close examination of these highly coloured reaction mixtures indicated the presence of crystals of A,A-dimethyl-A,A-diphenyltetrazene 65 (Scheme 11, R = Bu). The reaction is promoted by polar solvents as reactants are unchanged in pure acetonitrile. A crossover experiment using a mixture of /V- a ce t o x y - A-- b u t o x y - to 1 u a m i d e 26d and A-acetoxy-A-ethoxybenz-amide 25a afforded clean yields of butyl /Moluatc and ethyl benzoate thus pointing to an intramolecular rearrangement.41... 

Treatment of A-acyloxy-A-alkoxybenzamides 76a with dilute aqueous sodium hydroxide, at room temperature, resulted in the rapid formation of alkyl benzoates 67.40 A crossover experiment using A-acetoxy-A-butoxy-/ -chlorobenzamide 26e and A-acetoxy-A-benzyloxybenzamide 27a resulted in the exclusive formation of butyl / -chlorobenzoate (46%) and benzyl benzoate (43%) esters along with the hydrolysis products, / -chlorobenzoic acid and benzoic acid indicating that ester formation involves an intramolecular process. 

Three different isomers are formed consecutively on reacting [RuCl2(PPh3)3] with 4,6 -bis(pyrazol-l-yl)pyrimidine, bpzpm the final product is cis,trons-[RuCl2(PPh3)2(bpzpm)] (160). Nuclear magnetic resonance spectroscopy (NMR) shows facile cis < - trans interconversion for [H(dtbp)Ru(p-Cl)2Ru(dtbp)H], where dtbp = bis[di(t-butyl)phosphano-methane or -ethane. Crossover experiments implicate mononuclear intermediates in these isomerizations (161). 

The products of reductive cyclization incorporate two non-exchangeable hydrogen atoms. Homolytic and heterolytic hydrogen activation pathways may now be discriminated on the basis of hydrogen-deuterium crossover experiments. Reductive cyclization of the indicated nitrogen-tethered enyne under a mixed atmosphere... 

Scheme 22.19 Mechanistic studies involving hydrogen-deuterium crossover experiments, along with the observance of non-conjugated cycloisomerization products, suggest that rhodium (III) metallocyclopentene formation occurs in advance of hydrogen activation.

The mechanism proposed for this transformation is outlined in Scheme 24 (235). The slow step of this reaction is silyl transfer from the copper alkoxide 353. This step may occur through the intermediacy of an external silicon source (intermolecular) or by internal transfer of the silyl group (intramolecular). To probe this issue, these workers conducted a double-crossover experiment involving two distinct nucleophiles with different silyl groups, 342a and 359, and examined the products prior to desilylation. The results show conclusively that silicon transfer has a significant intermolecular component, and is somewhat sensitive to the solvent, Eq. 199. 

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