Side and Subsequent Reactions

Mono-metallation of most simple acetylenic compounds in organic solvents can be accomplished without complications. The same holds for reactions of RCsCH with alkali amides in liquid ammonia. However, HCsCSiR3 and HC=CSnR3 cannot be metallated in this way, because the bonds between C and Si and between C and Sn are cleaved. HCsCSeR and HC=CPR2 disproportionate into HCsCH and RSeCsCSeR or R2PCsCPR2, respectively, under the influence of alkali amides [40,102], 

The metallation of 3,1-enynes and 1,3-diynes with butyllithium requires careful experimentation, because dilithiation (and in the case of the enynes subsequent dimerization) occurs when the base is present in excess [2,41]  

In liquid ammonia with alkali amides, or in Et20 or THF with lithium dialkylamides, these complications do not occur, because these bases are considerably weaker than BuLi. 

Vinylacetylene, H2C=CHC=CH, undergoes a fast oligomerization if it is treated with a slight excess of BuLi [1]. 

This process can be avoided if the solution of BuLi is cautiously added to a small excess of. vinylacetylene. Alkali amides or lithium dialkylamides do not cause such an oligomerization. 

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The procedure described below is quite general and uses finely, freshly machine--powdered KOH, which is added to a solution of the primary or secondary (acetylenic) alcohol and a 10-15% molar excess of tosyl chloride in Et20, kept around 0 C The excess of tosyl chloride is destroyed during the reaction of the excess of KOH. Side- and subsequent reactions ("saponification of the ester by KOH and 1,2-elimination of p-toluenesulfonic acid from thtfester) can be suppressed by keeping the temperature of the reaction mixture below 5 C. This procedure can be carried out within 2 h and generally gives excellent (often almost quantitative) yields of the tosylates. Purification of acetylenic tosylates by distillation, which is risky because of the limited thermal stability of the esters, is not necessary because the... 

The Michael reaction is the conjugate addition of a soft enolate, commonly derived from a P-dicarbonyl compound 24, to an acceptor-activated alkene such as enone 41a, resulting in a 1,5-dioxo constituted product 42 (Scheme 8.14) [52]. Traditionally, these reactions are catalyzed by Bronsted bases such as tertiary amines and alkali metal alkoxides and hydroxides. However, the strongly basic conditions are often a limiting factor since they can cause undesirable side- and subsequent reactions, such as aldol cyclizations and retro-Claisen-type decompositions. To address this issue, acid- [53] and metal-catalyzed [54] Michael reactions have been developed in order to carry out the reactions under milder conditions. 

For solubilities of metallated acetylenic compounds see Table I on page 37. 2. Side- and Subsequent Reactions... 

Whereas iodinations of polar organometallic compounds in most cases are carried out with elemental iodine (see for example Exp. 40) the aggressive nature of chlorine may give rise to side and subsequent reactions, or reactions with the organic solvent. However, there are a number of compounds, containing so-called positive... 

Sequence-specific heteropolymers, as a class of synthetic molecules, are unique in that they must be made by chemical steps that add one monomer unit at a time. Moreover, to create truly protein-like structures, which typically have chain lengths of at least 100 monomers and a diverse set of 20 side chains (or more), extremely efficient and rapid coupHngs under general reaction conditions are necessary. For these reasons, soHd-phase synthesis is typically used, so that excess reagents can be used to drive reactions to completion, and subsequent reaction work-ups are quite rapid. 

In the presence of 02, most radicals are converted into the corresponding per-oxyl radicals with the notable exception of heteroatom-centered radicals which do not react with 02 at an appreciable rate (Chap. 8.2). However, even though peroxyl radical reactions may dominate in the reactions induced by the autoxi-dation of Fe(II)EDTA or Fe(II)NTA (Chap. 2.5), in the case of 2 -deoxynucleo-sides the subsequent reactions seem to be considerably modified by the presence of the transition metal ion, i.e. product ratios are found in these reactions which are different from those observed by ionizing radiation in the absence of Fe(II)/ Fe(III) (Murata-Kamiya et al. 1998). A basis for understanding these differences may be the various redox reactions that the peroxyl radicals will undergo with Fe(II)/Fe(III) (cf. Yurkova et al. 1999 Theruvathu et al. 2001 see also Chaps 2.5 and 8.3). 

A common explanation of the DMAP acceleration suggests that DMAP, as a stronger nucleophile than the alcohol, reacts with the O-acylisourea leading to a reactive amide ( active ester ). This intermediate cannot form intramolecular side products but reacts rapidly with alcohols. DMAP acts as an acyl transfer reagent in this way, and subsequent reaction with the alcohol gives the ester. 

Determination of Concentration For a simple reaction, as shown in Equation (1), the reaction rate can actually be measured at any time during the reaction. However, one prefers to measure at small conversion to reduce the error of to a minimum and so that c/c i,, cIca,Many reactions consist of a reaction network, including parallel and subsequent reactions. For such cases, small conversions are necessary to avoid falsification of the desired reaction rate by undesired side and/or subsequent reactions. 

In the reaction of a-diketones with formamide and formaldehyde at 180°-200°C, no a-hydroxyketones can be detected during the reaction,65 and hence formaldehyde cannot be acting as a reducing agent. It seems then that imidazole formation must be due to generation of ammonia from formamide and subsequent reaction between the diketone, ammonia, and formaldehyde. The advantage of this method over the older Radziszewski synthesis lies in the reduced decomposition of the diketone with consequent reduction in side, reactions which normally produce mixtures of imidazoles. 

Transition metal catalysis of the Michael reaction of 1,3-dicarbonyl compounds with acceptor activated alkenes has been known since the early 1980 s 2>3 It is a valuable alternative to the classic base catalysis of the reaction. Because of the mild and neutral conditions, the chemoselectivity of these reactions is superior to that provided by base catalysis, since the latter suffers from various unwanted side or subsequent reactions, such as aldol cyclizations, ester solvolyses or retro-Claisen type decompositions. A number of transition metal and lanthanide compounds have been reported to catalyze the Michael reaction, but FeCb 6 H20 is one of the most efficient systems to date. A number of 3-diketones or p-oxo esters and MVK are cleanly converted to the corresponding Michael reaction products within a few hours at room... 

A further noteworthy side reaction of palladium-catalyzed methylenecyclopropane cycloadditions is the isomerization of 2-(n-alkyl) methylenecyclopropanes to isoprene-type dienes, and subsequent reaction of the latter with electron-deficient alkenes to form cyclohexenes in a Diels — Alder reaction, rather than providing [3 + 2]-addition products. 

This hydrocarboration method is a valuable tool in industrial and laboratory synthesis, since it allows introduction of the one-carbon unit of carbon monoxide into unsaturated substrates and construction of new carbon skeletons with aldehyde functions or derivatives thereof formed by reduction, oxidation, condensation and other conversions. Hydroformylation, mainly catalyzed by cobalt, rhodium, or platinum complexes is an unsymmetrical 1,2-addition leading to linear and branched products if terminal olefins are used as the substrate. Since linear products are normally the industrial products wanted54, considerable efforts have concentrated on the control of regiochemistry. Other problems of the hydroformylation method arise from side reactions such as hydrogenation, double bond migration, and subsequent reactions of the products (e.g., condensation, reduction, dccarbonylation)54. 

Regioselective formation of the tosylhydrazone dianion was observed in tosylhydrazones of the type 111 derived from unsymmetrical ketones such as 2-butanone. Abstraction of protons from the less hindered side of 111 and subsequent reaction with acetone gave a / -hydroxytosylhydrazone, which on treatment with alkyllithium gave the homoallylic alcohol 112 in good yield as shown in equation 58s 3. Another example is shown in equation 59. 

The deprotonations with LDA are generally extremely fast, even at temperatures far below 0 °C and side- or subsequent reactions such as displacement of the OR group in carboxylic esters, or self-condensations, respectively, remain limited to a minimum. Enolates derived from lactones, e.g., y-butyrolactone, are extremely unstable and must be generated and functionalized below — 70 °C [7]. 

Narasimhan et al. (194) instituted a new approach to the synthesis of furoquinoline alkaloids by introducing a C2 side chain into a preformed quinoline nucleus. Lithiation of 2,4-dimethoxyquinoline, 2,4,6-tri-methoxyquinoline, and 2,4,8-trimethoxyquinoline with n-butyllithium in ether and subsequent reaction with ethylene oxide furnished hydroxyethyl derivatives 237, which with 20% hydrochloric acid were converted into dihydrodictamnine (239), dihydropteleine (240), and dihydro-y-fagarine... 

A dye component that is used frequently is H acid (l-amino-8-hydroxynaphthalene-3,6-disulfonic acid). Production of this comparatively complex substitution pattern requires a series of different chemical reactions. The known side reactions and subsequent reactions on sulfonation and nitration of the naphthalene system and high-pressure hydrolysis of its substituents reduce the yield of the target product. If, as a consequence, intermediate isolations are unavoidable during the course of the process to prevent a gradual increase in the amount of by-products, additional product losses in mother and wash liquors will occur. Management of the often considerable quantities of solid waste and wastewater is therefore an important consideration in the production of H acid. 

The determination of the total rate constant k of the process RO2 + NO -> RO + N02/nitrate from the shape of iQ 02 ) is essentially based on the first-order law [NO2KO = [N02]oo [1 exp(-fc [NO] 01- Corrections were made for the (slight) [NO]-decrease and for axial diffusion effects. Moreover, side-reactions such as RO2 + NO2 pernitrate, RO + NO nitrite, RO + NO2 nitrate, decomposition of RO and subsequent reactions, as well as contributions of nitrates and pernitrates to the total N02 signal, were duly taken into account by kinetic... 

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