Quenching addition reactions

In an altogether different type of approach, the hydrazone is formed in situ as a lithium salt. Wilson et al. (80JHC389) described this approach in the one-pot synthesis of 5-aryl-2-phenylpyrazol-3-ones 72a-f from the corresponding hydrazones 65a-f (Scheme 20). The latter were obtained by condensing ketones 64a-f with phenylhydrazine. Treatment of hydrazones 65a-f with n-butyllithium in dry THF, followed by the addition of half a molar equivalent of diethyl carbonate 67 and then quenching the reaction mixture with hydrochloric acid, produced pyrazol-3-ones 72a-f, along with products 71. The yields of the products 72 are in the range 22-97%. Four intermediates—66a-f, 68a-f, 69a-f, and 70a-f— were proposed for this reaction. 

A dicarbocyanine dye, dithiazinine (79), is used as a broad-spectrum anthelmentic agent, although, interestingly, it seems to have been prepared initially for use in photographic emulsions. It is made by heating 2-methylbenzothiazole ethiodide (77) with the malondialdehyde equivalent, B(ethylmercapto)-acrolein diethylacetal (78) in the presence of pyridine. There apparently ensues a sequence of addition-elimination reactions quenching the reaction mixture with potassium iodide solution results in separation of green crystals of dithiazanine iodide (79). ... 

The same high reactivity of radicals that makes possible the alkene polymerization we saw in the previous section also makes it difficult to carry out controlled radical reactions on complex molecules. As a result, there are severe limitations on the usefulness of radical addition reactions in the laboratory. Tn contrast to an electrophilic addition, where reaction occurs once and the reactive cation intermediate is rapidly quenched in the presence of a nucleophile, the reactive intermediate in a radical reaction is not usually quenched, so it reacts again and again in a largely uncontrollable wav. 

Electrophilic addition (Intermediate is quenched, so reaction stops. ... 

C in a TH F-toluene-hexane mixture. After the mixture was cooled below —50 °C, ketone 41 was added. After 60min, the reaction was quenched with aqueous citric acid. The organic layer was then solvent switched into toluene, and the product 50 was crystallized by the addition of heptane (91-93% isolated yield, >99.5% ee). The chiral modifier 46 is easily recycled from the aqueous layer by basification with NaOH and extraction into toluene to recover 46 (>99% purity, 98% recovery yield). The modifier has been recycled up to nine times in subsequent chiral addition reactions without any problem. 

The IR showed the complete disappearance of the OH stretch of 46 after 0.5 equiv of Red-AI was added. Quenching the reaction at this stage resulted only in the recovery of starting material. However, the addition of an additional 1.0 equiv of Red-Ad to intermediate 83 led to the rapid formation of 48 and 10. It was speculated that the addition of the excess Red-AI led to the formation of 84 [31], where... 

When we allowed pentafluorophenyl-lithium to decompose in ether in the presence of an excess of N, ZV-dimethy laniline we obtained the compounds (92) 70, X = F), (94), the latter as the major compound, and a product which was shown to be (97). That this latter compound did not arise by metallation of 2V,lV-dimethylaniline followed by addition to tetrafluorobenzyne was shown by quenching the reaction mixture with deuterium oxide. No deuterium incorporation was detected. The compound (97) provides a rare example of a product derived by a Stevens rearrangement in which aryl migration has occurred b>. 

Quench the reaction by immediate gel filtration on a desalting column. If a dextran-based resin is used for the chromatography, the support itself will react with sodium periodate to quench excess reagent. Alternatively, N-acetylmethionine may be added to quench the reaction, because the thioether of the methionine side chain will react with periodate to form sulfoxide or sulfone products (Geoghegan and Stroh, 1992). In addition, sodium... 

Immediately quench the reaction by the addition of sodium sulfite (Na2S03) to provide a 2X molar excess over the initial amount of periodate added. Purify the oxidized antibody by gel filtration using a desalting resin. The chromatography buffer is 0.1 M sodium phosphate, 0.15M NaCl, pH 7.2. To obtain efficient separation between the oxidized antibody and excess periodate, the sample size applied to the column should be at a ratio of no more than 5 percent sample volume to the total column volume. Collect 0.5 ml fractions and monitor for protein at 280 nm. 

Quench the reaction by the addition of NH4HCO3 to a final concentration of 20 mM. The optimal time course for the reaction should be determined by removing portions of the solution at different points, starting at about 5-10 minutes and extending out to 2 hours in length. 

Quench the cleavage reaction by the addition of an equal volume of SDS electrophoresis sample buffer containing up to 40 percent glycerol. The SDS will denature the protein interaction and glycerol acts as a free radical scavenger, thus effectively quenching the reaction. 

Competition Experiments of Ley Ley examined product distributions to obtain relative reactivity values (RRVs) for both rhamnose and mannose sugars with benzyl, 3,4-cyclic diacetals, and benzoyl groups. Using a limiting amount of acceptor (1 equiv), two donors were added in excess (2 equiv each), followed by the addition of activator (NIS/TfOH, 2 equiv) (Scheme 11.13). After quenching the reaction, the product distribution was analyzed by -NMR. 

An allenyllithium intermediate was implicated in the reaction of BuLi with an alkynylated cyclohexene epoxide (Table 9.5) [11], It was found that addition of 2equiv. of BuLi to the alkynyloxirane in the presence of 5mol% CuBr-2PPh3 led, after quenching with H20, not to the expected SN2 butylated allene, but instead to the protonolysis product. Likewise, quenching the reaction with Mel or MeSSMe led to the methylated and thiolated allenes, respectively. Furthermore, the putative lithioallene could be trapped by C02 or PhCHO to yield the expected adducts. 

The addition of allenyl ether-derived anions to Weinreb [4] or to morpholino amides [5] follows a slightly different pathway (Eq. 13.2). For example, the addition of lithioallene 6 to Weinreb amide 7 at -78 °C, followed by quenching the reaction with aqueous NaH2P04 and allowing the mixture to warm to room temperature leads to cyclopentenone 9 in 80% yield [6]. The presumed intermediate of this reaction, allenyl vinyl ketone 8, was not isolated, as it underwent cyclization to 9 spontaneously [7]. These are exceptionally mild conditions for a Nazarov reaction and are probably a reflection of the strain that is present in the allene function, and also the low barrier for approach of the sp and sp2 carbon atoms. What is also noteworthy is the marked kinetic preference for the formation of the Z-isomer of the exocyclic double bond in 9. Had the Nazarov cyclization of 8 been conducted with catalysis by strong acid, it is unlikely that the kinetic product would have been observed. 

Allenamide ( )-13 was prepared by trapping the corresponding lithioallene with carbon dioxide, followed by conversion of the carboxylate to the amide. Chromatographic resolution of the enantiomers of 13 was easily accomplished on a 10x250mm Chiralcel OD HPLC column. Addition of vinyllithium 14 to (+)-13, followed by quenching the reaction with aqueous NaH2P04, led to cyclopentenone (—)-15 in 64% yield with >95% chirality transfer (Eq. 13.4). The absolute stereochemistry of (-)-5 is consistent with the mechanistic hypothesis put forth in Eq. 13.3 [8]. 

The use of ethylene adduct lb is particularly important when the species added to activate catalyst la is incompatible with one of the reaction components. Iridium-catalyzed monoallylation of ammonia requires high concentrations of ammonia, but these conditions are not compatible with the additive [Ir(COD)Cl]2 because this complex reacts with ammonia [102]. Thus, a reaction between ammonia and ethyl ciimamyl carbonate catalyzed by ethylene adduct lb produces the monoallylation product in higher yield than the same reaction catalyzed by la and [Ir(COD)Cl]2 (Scheme 27). Ammonia reacts with a range of allylic carbonates in the presence of lb to form branched primary allylic amines in good yield and high enantioselectivity (Scheme 28). Quenching these reactions with acyl chlorides or anhydrides leads to a one-pot synthesis of branched allylic amides that are not yet directly accessible by metal-catalyzed allylation of amides. 

The Sjjf.fl character of the reaction was ascertained by the effect of light irradiation and addition of a radical trap. Namely, under light irradiation, the half-reaction time was considerably shortened (3 instead of 41 min). Addition of di(tert-butyl)nitroxide completely quenched the reaction—neither C- nor 0-substitution was observed after 4 h. The radical trap may only react with the R radicals that escaped the solvent cage where R, Nu, and X have been formed. This means that, in the... 

Phenylpyrimidine. On treatment of 4-phenylpyrimidine with potassium amide in liquid ammonia at 33°C for 70 hr in the presence of potassium nitrate, followed by quenching the reaction mixture by addition of ammonium chloride and workup, two products were isolated 2-amino-4-phenylpyrimidine (60%) and 6-amino-4-phenylpyrimidine (15%) (79JOC4677). When the reaction was carried out with labeled potassium amide in liquid ammonia and using the combined methodologies of chemical conversions and mass spectrometry as discussed previously (see Section II,C,l,a) it was found that in 6-amino-4-phenylpyrimidine (62/63), hardly any label was incorporated in the ring ( 5%), but that about... 

---