Solvents aprotic, substitution

The same conclusion was reached in a kinetic study of solvent effects in reactions of benzenediazonium tetrafluoroborate with substituted phenols. As expected due to the difference in solvation, the effects of para substituents are smaller in protic than in dipolar aprotic solvents. Alkyl substitution of phenol in the 2-position was found to increase the coupling rate, again as would be expected for electron-releasing substituents. However, this rate increase was larger in protic than in dipolar aprotic solvents, since in the former case the anion solvation is much stronger to begin with, and therefore steric hindrance to solvation will have a larger effect (Hashida et al., 1975 c). 

In the case of cyclic tertiary enaminones as dienophiles in the reaction with nitroalk-enes as heterodienes, [4 + 2]-cycloaddition yields tetrahydrobenzo >][l,2]oxazin-8-ones nearly quantitatively. Heating in aprotic solvents affords substituted diaster-eoisomeric pentalenones by ring contraction of the six-membered ring326 (equation 244). 

Depending on their location on a sugar, sulfonates have very different reactivities. This is apparent, for example, in the behaviour of tosylates. The tosylate of the primary alcohol function can be substituted without difficulty, even in solvents which are not polar or aprotic. Substitution at positions 3 and 4 are only possible in DMF solution. Substitution at position 2 is absolutely impossible. On the other hand, it is often observed without problems at position 2 starting from a triflate or an imidazylate. These reactivity differences clearly appear in the triple substitution reaction of the tris-triflate P-D-galacto 7 J by benzoate (Alais and David 1990). The latter is prepared from the triol in 5 h at 0 C. It reacts quantitatively with tetrabutylammonium benzoate in toluene in 45 min at room temperature to give the D-gluco substitution product at C-4 and C-6. Heating for 1 h at 100 C then leads to the D-manno tribenzoate 74. 

The reactions of ( )-styryl(phenyl)iodonium salt 37 with halide ions give results similar to those obtained with 50 (Scheme 49, Table 14)." In this case the main product is that of elimination. In aprotic solvents the substitution products (79) are predominantly inverted but in TFE a significant amount of retained 79 was also... 

In reactions of tertiary halides, unimolecular processes dominate in protic solvents (especially water and aqueous solvent mixtures) where substitution is usually faster than elimination. Substitution involves nucleophilic attack directly at a cationic center, whereas elimination involves removal of an acidic hydrogen two bonds removed from the cationic atom, explaining the difference. Clearly, a nucleophilic species is strongly attracted to the most positive center and that should lead to the major product. In aprotic solvents, bimolecular substitution is not observed for tertiary halide due to the high energy required to form the pentacoordinate transition state (sec. 2.7.A.i). Under conditions that favor bimolecular reactions and in the presence of a suitable base, elimination is the dominant process. 

In dipolar aprotic solvents partially substituted ammonium cations, i nH4 nN , can form internal hydrogen bonds with small anions, " thus increasing their association. PhHgNPic is more associated than i NPic in and its low A° suggests that two dissociation equilibria... 

The nucleophilicity of anions, in general, depends very much on the degree of solvation. Much of the data that form the basis for quantitative measurement of nucleophilicity is for reactions in hydroxylic solvents. In protic, hydrogen-bonding solvents, anions are subject to strong interactions with solvent. Hard nucleophiles are more strongly solvated by protic solvents than soft nucleophiles, and this difference contributes to the greater nucleophilicity of soft anions in such solvents. Nucleophilic substitution reactions often occur more readily in polar aprotic solvents than they do in protic solvents. This is because anions are weakly solvated in such... 

Secondary halides can undergo both unimolecular and bimo-lecular reactions, as well as substitution and elimination. Elimination is favored in protic solvents and substitution is favored in aprotic solvents. 

In an aprotic solvent, both 8n2 and E2 reactions are favorable for a secondary halide. Are there reaction conditions that will favor substitution over elimination or elimination over substitution Yes The nature of the solvent will favor one over the other, so a last question may be asked Is the solvent for the reaction of a secondary halide protic or aprotic Aprotic solvents favor bimolecular reactions and, because substitution is a faster process than elimination, assume that aprotic solvents favor substitution. If a secondary halide is treated with sodium methoxide in THE, the solvent is aprotic, and the 8fj2 reaction is assumed to give the major product. This is the Williamson ether synthesis in Chapter 11, 8ection 11.3.2. 

Specific solvation is of great importance. Aprotic solvents do not virtually solvate an ion. This strongly facilitates its attack at the positively charged carbon atom of the RX substrate. Therefore, in aprotic solvents nucleophilic substitution occurs espe-... 

Solvent Effects on the Rate of Substitution by the S 2 Mechanism Polar solvents are required m typical bimolecular substitutions because ionic substances such as the sodium and potassium salts cited earlier m Table 8 1 are not sufficiently soluble m nonpolar solvents to give a high enough concentration of the nucleophile to allow the reaction to occur at a rapid rate Other than the requirement that the solvent be polar enough to dis solve ionic compounds however the effect of solvent polarity on the rate of 8 2 reactions IS small What is most important is whether or not the polar solvent is protic or aprotic Water (HOH) alcohols (ROH) and carboxylic acids (RCO2H) are classified as polar protic solvents they all have OH groups that allow them to form hydrogen bonds... 

The large rate enhancements observed for bimolecular nucleophilic substitutions m polai aprotic solvents are used to advantage m synthetic applications An example can be seen m the preparation of alkyl cyanides (mtiiles) by the reaction of sodium cyanide with alkyl halides... 

Rate increases with increasing po larity of solvent as measured by its dielectric constant e (Section 8 12) Polar aprotic solvents give fastest rates of substitution solvation of Nu IS minimal and nucleophilicity IS greatest (Section 8 12)... 

New heat-resistant polymers containing -iiitrophenyl-substituted quinoxaline units and imide rings as well as flexible amide groups have been synthesi2ed by polycondensation reaction of a dianainoquinoxaline derivative with diacid dichlorides (80). These polymers are easily soluble in polar aprotic solvents with inherent viscosities in the range of 0.3—0.9 dL/g in NMP at 20°C. AH polymers begin to decompose above 370°C. 

Condensation ofDianhydrides with Diamines. The preparation of polyetherknides by the reaction of a diamine with a dianhydride has advantages over nitro-displacement polymerization sodium nitrite is not a by-product and thus does not have to be removed from the polymer, and a dipolar aprotic solvent is not required, which makes solvent-free melt polymerization a possibiUty. Aromatic dianhydride monomers (8) can be prepared from A/-substituted rutrophthalimides by a three-step sequence that utilizes the nitro-displacement reaction in the first step, followed by hydrolysis and then ring closure. For the 4-nitro compounds, the procedure is as follows. 

Nucleophilic Substitution Route. Commercial synthesis of poly(arylethersulfone)s is accompHshed almost exclusively via the nucleophilic substitution polycondensation route. This synthesis route, discovered at Union Carbide in the early 1960s (3,4), involves reaction of the bisphenol of choice with 4,4 -dichlorodiphenylsulfone in a dipolar aprotic solvent in the presence of an alkaUbase. Examples of dipolar aprotic solvents include A/-methyl-2-pyrrohdinone (NMP), dimethyl acetamide (DMAc), sulfolane, and dimethyl sulfoxide (DMSO). Examples of suitable bases are sodium hydroxide, potassium hydroxide, and potassium carbonate. In the case of polysulfone (PSE) synthesis, the reaction is a two-step process in which the dialkah metal salt of bisphenol A (1) is first formed in situ from bisphenol A [80-05-7] by reaction with the base (eg, two molar equivalents of NaOH),... 

Isoquinoline can be reduced quantitatively over platinum in acidic media to a mixture of i j -decahydroisoquinoline [2744-08-3] and /n j -decahydroisoquinoline [2744-09-4] (32). Hydrogenation with platinum oxide in strong acid, but under mild conditions, selectively reduces the benzene ring and leads to a 90% yield of 5,6,7,8-tetrahydroisoquinoline [36556-06-6] (32,33). Sodium hydride, in dipolar aprotic solvents like hexamethylphosphoric triamide, reduces isoquinoline in quantitative yield to the sodium adduct [81045-34-3] (25) (152). The adduct reacts with acid chlorides or anhydrides to give N-acyl derivatives which are converted to 4-substituted 1,2-dihydroisoquinolines. Sodium borohydride and carboxylic acids combine to provide a one-step reduction—alkylation (35). Sodium cyanoborohydride reduces isoquinoline under similar conditions without N-alkylation to give... 

Anodic Oxidation. The abiUty of tantalum to support a stable, insulating anodic oxide film accounts for the majority of tantalum powder usage (see Thin films). The film is produced or formed by making the metal, usually as a sintered porous pellet, the anode in an electrochemical cell. The electrolyte is most often a dilute aqueous solution of phosphoric acid, although high voltage appHcations often require substitution of some of the water with more aprotic solvents like ethylene glycol or Carbowax (49). The electrolyte temperature is between 60 and 90°C. 

When R = H, in all the known examples, the 3-substituted tautomer (129a) predominates, with the possible exception of 3(5)-methylpyrazole (R = Me, R = H) in which the 5-methyl tautomer slightly predominates in HMPT solution at -17 °C (54%) (77JOC659) (Section 4.04.1.3.4). For the general case when R = or a dependence of the form logjRTT = <2 Za.s cTi + b Xa.s (Tr, with a>0,b <0 and a> b, has been proposed for solutions in dipolar aprotic solvents (790MR( 12)587). The equation predicts that the 5-trimethylsilyl tautomer is more stable than the 3-trimethylsilylpyrazole, since experimental work has to be done to understand the influence of the substituents on the equilibrium constant which is solvent dependent (78T2259). There is no problem with indazole since the IH tautomer is always the more stable (83H(20)1713). 

The realization that die nucleophilicity of anions is strongly enhanced in polar aprotic solvents has led to important improvements of several types of synthetic processes that involve nucleophilic substitutions or additions. 

Neopentyl (2,2-dimethylpropyl) systems are resistant to nucleo diilic substitution reactions. They are primary and do not form caibocation intermediates, but the /-butyl substituent efiTectively hinders back-side attack. The rate of reaction of neopent>i bromide with iodide ion is 470 times slower than that of n-butyl bromide. Usually, tiie ner rentyl system reacts with rearrangement to the /-pentyl system, aldiough use of good nucleophiles in polar aprotic solvents permits direct displacement to occur. Entry 2 shows that such a reaction with azide ion as the nucleophile proceeds with complete inversion of configuration. The primary beiuyl system in entry 3 exhibits high, but not complete, inversiotL This is attributed to racemization of the reactant by ionization and internal return. 

Sodium acetate reacts with /p-nitrophenyl benzoates to give mixed anhydrides if the reaction is conducted in a polar aprotic solvent in the presence of a crown ether. The reaction is strongly accelerated by quartemary nitrogen groups substituted at the orthc position. Explain the basis for the enhanced reactivity of these compounds. 

Other measures of nucleophilicity have been proposed. Brauman et al. studied Sn2 reactions in the gas phase and applied Marcus theory to obtain the intrinsic barriers of identity reactions. These quantities were interpreted as intrinsic nucleo-philicities. Streitwieser has shown that the reactivity of anionic nucleophiles toward methyl iodide in dimethylformamide (DMF) is correlated with the overall heat of reaction in the gas phase he concludes that bond strength and electron affinity are the important factors controlling nucleophilicity. The dominant role of the solvent in controlling nucleophilicity was shown by Parker, who found solvent effects on nucleophilic reactivity of many orders of magnitude. For example, most anions are more nucleophilic in DMF than in methanol by factors as large as 10, because they are less effectively shielded by solvation in the aprotic solvent. Liotta et al. have measured rates of substitution by anionic nucleophiles in acetonitrile solution containing a crown ether, which forms an inclusion complex with the cation (K ) of the nucleophile. These rates correlate with gas phase rates of the same nucleophiles, which, in this crown ether-acetonitrile system, are considered to be naked anions. The solvation of anionic nucleophiles is treated in Section 8.3. 

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