Preventing Side Reactions

Because of 1,2-hydride and alkyl shifts, it is possible to obtain multiple products from SnI reactions. Thus, to induce one product to predominate, we must find a way to stabilize the carbocation. This is done by using highly polar solvents such as acetic acid, dimethyl formamide, and dimethyl sulfoxide. In using this strategy, the lifetime of a carbocation can be extended, allowing the most stable product more time to form. As a result, 

In this chapter, SN l reactions were introduced, compared to SN2 reactions and discussed mechanistically. Through these discussions, the involvement of electron orbitals, and their various hybrids, was addressed. Furthermore, complicating side reactions such as hydride and alkyl migrations were presented. As discussions move into more advanced mechanistic types, it is important to maintain awareness of the involvement and orientation of orbitals, the steric environment at reactive centers, and the overall reactivity of nucleophiles and electrophilic centers. 

For the following molecules, state the hybridization (sp, sp2, sp3) of the orbitals associated with the highlighted bond. Also, state the geometry of the bound atomic centers (linear, bent, trigonal planar, tetrahedral). 

For each of the following reactions, determine which will proceed via an SN1 or an Sn2 mechanism. In cases where both may be applicable, list appropriate reaction conditions (e.g., solvents, reagents) that would favor SN1 over SN2 and vice versa. Explain your answers. 

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The diphenyl ester of the diacid [XI] is used to prevent side reactions such as decarboxylation. 

The reaction temperature should be kept below 20°C to prevent side reactions. If the temperature exceeds 20°C, one should stop both the addition of the prenyl chloride and the ultrasound irradiation, and wait for the reaction temperature to fall below 15°C. 

Ammonium salts must be removed to prevent side reactions, in particular the formation of iminium on aldehydes. 

Formation of the nucleoside phosphorodichloridite at -30 °C by PCI3 in CH2CI2 solution (step a) is followed by reaction with ethanol (step b). Subsequently dealkylation occurs with the assistance of hydrogen chloride formed in reaction (a) to give the desired 5 -nucleoside H-phosphonate (step c). It was found that a mixture of ethanol and tcrt-butanol (1 1) as alcoholysis agent prevented side reactions and gave a higher yield than when ethanol alone was used. 

Br prevents side reactions and makes BiBr3 a better Lewis acid catalyst, which is in accordance with our work BiBr3 affords only Ritter reaction products in the high dielectric constant solvent CH3CN, while BiCl3 originates a mixture of both v7 -/V-acylamino-hydroxy compounds and chlorohydrins. 

In contrast, a persistent carbocation could not be generated from 9,10-dihydro-BaP introduction of bulky substituents at C-6 prevented side reactions, and the initially formed carbocation underwent rearrangement to the corresponding bay-region carbocation. Introduction of methoxy substituents into the 1- or 3- positions of 9,10-dihydro-BaP-7(8//)-one increased its electrophilic reactivity to the extent that stable carboxonium-arenium dications were produced in FSO3H/SO2CIF (Fig. 9). 

On the other hand, It sometimes happens that the nucleo-philicity of the end standing precursor carbanlon has to be decreased to prevent side reactions. An easy way to achieve that is an Intermediate addition of 1,l-diphenylethylene." This procedure Is used especially when the second monomer to be added Is a methacryllc ester, to prevent attack of the ester carbonyl. 

The mechanism by which the more recently used WR-2721 (Fig. 8) reduces nephrotoxicity is not very well understood. WR-2721 protects against nephrotoxicity when administered just prior to cis-Pt (144,145) and it is known that WR-2721 is preferentially taken up by normal cells and not by tumor cells (146). Recently, it was concluded that the uncharged form of the dephosphorylated WR-2721 (known as WE-1065) is the actual species taken up by both normal and tumor cells (147). It has been proposed that the conversion of WR-2721 to WR-1065 is slower in tumors, compared with normal tissues (147), possibly because tumors generally have lower levels of alkaline phosphatase (148). Furthermore, it has been proposed (147) that once formed, WR-1065 will have a decreased uptake rate in tumors, probably as a consequence of their lower pH (149) as compared with normal tissues i.e., the neutral form of WR-1065 will only constitute 0.1% of the total drug present at pH 7 and 1% of the total at pH 8. The reactive WR-1065 is likely to bind directly to cis-Pt, thereby preventing side reactions of cis-Pt. 

A much more general method for acyl silane synthesis involving silyl diazo intermediates is illustrated in Scheme 1688. The lithiated derivative of trimethylsilyl diazomethane reacts smoothly with alkyl halides in THF solution to give a-trimethylsilyl diazoalkanes in good yields. Oxidative cleavage of the diazo moiety is effected using 3-chloroperbenzoic acid in benzene solution, to give access to a wide variety of acyl silanes in yields of up to 71%. A phosphate buffer (pH 7.6) is used to prevent side reactions. Aromatic acyl silanes clearly cannot be prepared by this chemistry since an aromatic nucleophilic substitution reaction would be required. 

Oxygenation of allylic alcohols. This Ru(II) complex, as well as RuBr2[P(C6H5)3]3 and RuH(OAc)[P(C6H5)3]3, catalyzes the oxidation of allylic alcohols to 2,/J-unsaturated ketones or aldehydes by molecular oxygen with retention of configuration. The oxidation of retinol to retinal (second example) requires addition of 2,6-dimethylpyridine to prevent side reactions.2... 

The pH of the solution should be exactly calibrated by means of a pH meter in order to prevent side reactions. The use of pH paper is not recomnended. 

A limited set of phenylenediamine color developers are used. Kodak s CD-3, CD-4, and CD-6 (26-28) are the principle color developers used today [31], They are directly incorporated into the alkaline processing fluid. The methyl group in the 2-position is important for preventing side reactions and enhancing the formation of the desired dye. The phenylenediamine undergoes a two-electron oxidation to quinonediimine, which then reacts with the color couplers to form the desired chromophores [32],... 

It is very important to keep the concentration of Br2 and HBr low to prevent side reactions derived from simple ionic addition with the alkene. These reagents are therefore generated in situ from NBS. The catalytically active species is Br2, which is almost always present in NBS samples (red colour). 

The reaction rates at the various positions on the ring vary greatly. For example, with TDI, the relative rates are shown in Figure 2.27. The reactions are exothermic, so the rate of addition must be controlled to prevent side reaction. 

Stabilizers are added to the system to prevent side reactions and gelation. The aim is to have the final system very slightly acidic (0.33 microequivalents... 

The reaction is reversible, but the equilibrium can be shifted to the point of complete reduction by removal of the acetaldehyde with a stream of dry hydrogen or nitrogen. This has the additional advantage of preventing side reactions such as an aldol condensation between the original aldehyde and acetaldehyde. The method of reduction with aluminum ethoxide was found applicable to several aldehydes but to only a few ketones of special types. 

With conventional protocols requiring low reaction temperatures, typically —78 °C, to prevent side reactions from occurring, scaling the reaction for industrial production of such compounds has proved difficult. As such, the authors evaluated the process under continuous flow, proposing that the effective temperature control and accurate residence times attainable within miniaturized flow reactors would enable the synthesis of diarylethenes at temperatures above — 78 °C and thus facilitate the large-scale synthesis of such compounds. 

Poly (benzyl ether) [G-2]-TEMPO, [G-3]-TEMPO, and [G-4]-TEMPO compounds have been synthesized and used as additives in the benzoyl peroxide initiated polymerization of styrene [127] (see Scheme 15c). After an induction period, chain growth is observed. However, the MWD is larger than in a dendrim-er-free TEMPO modulated system (Mw/Mn 2). The expectation that the den-drimer would isolate the growing chain end and prevent side reactions is not borne out. Polymerizations of methylmethacrylate, vinylacetate, and n-buty-lacrylate with the same initiator/TEMPO recipe are disappointing. 

The amine product plays a critical role, as it deprotonates the H2 complex 18 to regenerate the catalytically active 17. This also prevents side reactions based on nucleophilic ring opening of the aziridinium cations by the amine products. Alkyl substituted aziridinium cations react via a classical SN2-mechanism. 

The addition of urea to the reacting system prevents side reactions, e.g. the formation of nitrous esters. The yield amounts to about 60%. 

To prevent side reactions, the amino group of alanine must be protected to make it nonnucleophilic. In Section 24-7B, we saw that an amino acid reacts with benzyl chlo-roformate (also called benzyloxycarbonyl chloride) to form a urethane, or carbamate ester, that is easily removed at the end of the synthesis. This protecting group has been used for many years, and it has acquired several names. It is called the benzyloxycarbonyl group, the carbobenzoxy group (Cbz), or simply the Z group (abbreviated Z). 

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