Rates nucleophilic displacement

Higher perfluoroalkanesulfonates are slightly more reactive than triflates toward nucleophilic displacements. The rate constants for acetolysis of methyl nonafluorobutanesulfonate [6401 -03-2J, methyl trifluoromethanesulfonate [333-27-7] and methyl toluenesulfonate [80-48-8] are 1.49 x, ... 

Rate studies show that base-cataly2ed reactions are second order and depend on the phenolate and methylene glycol concentrations. The most likely path involves a nucleophilic displacement by the phenoxide on the methylene glycol (1), with the hydroxyl as the leaving group. In alkaline media, the methylolated quinone intermediate is readily converted to the phenoxide by hydrogen-ion abstraction (21). 

Solvent for Displacement Reactions. As the most polar of the common aprotic solvents, DMSO is a favored solvent for displacement reactions because of its high dielectric constant and because anions are less solvated in it (87). Rates for these reactions are sometimes a thousand times faster in DMSO than in alcohols. Suitable nucleophiles include acetyUde ion, alkoxide ion, hydroxide ion, azide ion, carbanions, carboxylate ions, cyanide ion, hahde ions, mercaptide ions, phenoxide ions, nitrite ions, and thiocyanate ions (31). Rates of displacement by amides or amines are also greater in DMSO than in alcohol or aqueous solutions. Dimethyl sulfoxide is used as the reaction solvent in the manufacture of high performance, polyaryl ether polymers by reaction of bis(4,4 -chlorophenyl) sulfone with the disodium salts of dihydroxyphenols, eg, bisphenol A or 4,4 -sulfonylbisphenol (88). These and related reactions are made more economical by efficient recycling of DMSO (89). Nucleophilic displacement of activated aromatic nitro groups with aryloxy anion in DMSO is a versatile and useful reaction for the synthesis of aromatic ethers and polyethers (90). 

Rates of debromination of bromonitro-thiophenes and -selenophenes with sodium thio-phenoxide and sodium selenophenoxide have been studied. Selenophene compounds were about four times more reactive than the corresponding thiophene derivatives. The rate ratio was not significantly different whether attack was occurring at the a- or /3-position. As in benzenoid chemistry, numerous nucleophilic displacement reactions are found to be copper catalyzed. Illustrative of these reactions is the displacement of bromide from 3-bromothiophene-2-carboxylic acid and 3-bromothiophene-4-carboxylic acid by active methylene compounds (e.g. AcCH2C02Et) in the presence of copper and sodium ethoxide (Scheme 77) (75JCS(P1)1390). 

The ortho indirect deactivating effect of the two methyl groups in 2,6-dimethyl-4-nitropyridine 1-oxide (163) necessitates a much higher temperature (about 195°, 24 hr) for nucleophilic displacement of the nitro group by chloride (12iV HCl) or bromide ions N HBr) than is required for the same reaction with 4-nitropyridine 1-oxide (110°). With 5-, 6-, or 8-methyl-4-chloroquinolines, Badey observed 2-7-fold decreases in the rate of piperidino-dechlorination relative to that of the des-methyl parent (cf. Tables VII and XI, pp. 276 and 338, respectively). 

Nucleophilic displacement reactions One of the most common reactions in organic synthesis is the nucleophilic displacement reaction. The first attempt at a nucleophilic substitution reaction in a molten salt was carried out by Ford and co-workers [47, 48, 49]. FFere, the rates of reaction between halide ion (in the form of its tri-ethylammonium salt) and methyl tosylate in the molten salt triethylhexylammoni-um triethylhexylborate were studied (Scheme 5.1-20) and compared with similar reactions in dimethylformamide (DMF) and methanol. The reaction rates in the molten salt appeared to be intermediate in rate between methanol and DMF (a dipolar aprotic solvent loiown to accelerate Sn2 substitution reactions). 

The diacyl peroxide-amine system, especially BPO-DMT or BPO-DMA, has been used and studied for a long time but still no sound initiation mechanism was proposed. Some controversy existed in the first step, i.e., whether there is formation of a charge-transfer complex of a rate-controlling step of nucleophilic displacement as Walling 1] suggested ... 

Qiu et al. [11] reported that the aromatic tertiary amine with an electron-rich group on the N atom would favor nucleophilic displacement and thus increase the rate of decomposition of diacyl peroxide with the result of increasing the rate of polymerization (Table 1). They also pointed out that in the MMA polymerization using organic peroxide initiator alone the order of the rate of polymerization Rp is as follows ... 

Streitweiser et al.597 have also measured second-order rate coefficients for hydrogen exchange of fluorobenzenes with sodium methoxide in methanol, Table 182. Nucleophilic displacement of fluoride ion by methoxide ion accompanies... 

Bordwell and Cooper211 drew attention to the inertness of a-halosulfones and related compounds towards nucleophilic displacements of the halogen. Thus chloromethyl p-tolyl sulfone reacts with potassium iodide in acetone at less than one-fiftieth of the rate for n-butyl chloride. On the other hand, l-(p-toluenesulfonyl)-3-chloro-l-propene reacts about 14 times faster than allyl chloride. This contrast (and other comparisons) led the authors to attribute the inertness of a-halosulfones to steric hindrance, which was eliminated when the sulfonyl group was more remote from the reaction center. 

Although the foregoing reactions involve dehalogenation by reduction or elimination, nucleophilic displacement of chloride may also be important. This has been examined with dihalomethanes using HS at concentrations that might be encountered in environments where active anaerobic sulfate reduction is taking place. The rates of reaction with HS exceeded those for hydrolysis and at pH values above 7 in systems that are in equilibrium with elementary sulfur, the rates with polysulfide exceeded those with HS. The principal product from dihalomethanes was the polythio-methylene HS (CH2-S) H (Roberts et al. 1992). 

Dimethylsulfonium methylide is both more reactive and less stable than dimethylsulfoxonium methylide, so it is generated and used at a lower temperature. A sharp distinction between the two ylides emerges in their reactions with a, ( -unsaturated carbonyl compounds. Dimethylsulfonium methylide yields epoxides, whereas dimethylsulfoxonium methylide reacts by conjugate addition and gives cyclopropanes (compare Entries 5 and 6 in Scheme 2.21). It appears that the reason for the difference lies in the relative rates of the two reactions available to the betaine intermediate (a) reversal to starting materials, or (b) intramolecular nucleophilic displacement.284 Presumably both reagents react most rapidly at the carbonyl group. In the case of dimethylsulfonium methylide the intramolecular displacement step is faster than the reverse of the addition, and epoxide formation takes place. 

Another difference between dimethylsulfonium methylide and dimethylsulfoxonium methylide concerns the stereoselectivity in formation of epoxides from cyclohexanones. Dimethylsulfonium methylide usually adds from the axial direction whereas dimethylsulfoxonium methylide favors the equatorial direction. This result may also be due to reversibility of addition in the case of the sulfoxonium methylide.92 The product from the sulfonium ylide is the result the kinetic preference for axial addition by small nucleophiles (see Part A, Section 2.4.1.2). In the case of reversible addition of the sulfoxonium ylide, product structure is determined by the rate of displacement and this may be faster for the more stable epoxide. 

The rate of appearance of p-nitrophenolate ion from p-nitrophenyl methylphosphonate (7), an anionic substrate, is moderately accelerated in the presence of cycloheptaamylose (Brass and Bender, 1972). The kinetics and pH dependence of the reaction are consistent with nucleophilic displacement of p-nitrophenolate ion by an alkoxide ion derived from a cycloheptaamylose hydroxyl group to form, presumably, a phosphonylated cycloheptaamylose. At 60.9° and pH 10, the cycloheptaamylose-induced rate acceleration is approximately five. Interestingly, the rate of hydrolysis of m-nitrophenyl methylphosphonate is not affected by cycloheptaamylose. Hence, in contrast to carboxylate esters, the specificity of cycloheptaamylose toward these phosphonate esters is reversed. As noted by Brass and Bender (1972), the low reactivity of the meta-isomer may, in this case, be determined by a disadvantageous location of the center of negative charge of this substrate near the potentially anionic cycloheptaamylose secondary hydroxyl groups. 

The most effective catalyst for the hydrolysis of p-nitrophenyl acetate was reported to be a cycloheptaamylose derivative containing approximately two imidazole groups per cycloheptaamylose molecule (Cramer and Mackensen, 1970). At pH 7.5 and 23°, this material accelerates the rate of release of phenol from p-nitrophenyl acetate by a factor of 300 when compared with the hydrolysis of this substrate in the absence of catalyst. However, when compared with an equivalent concentration of imidazole, which is an effective catalyst for ester hydrolysis at neutral pHs, the rate accelerations imposed by this cycloheptaamylose derivative are only two- to threefold. Cramer and Mackensen attributed this rate enhancement to nucleophilic displacement of phenol from the included ester by a cycloheptaamylose hydroxyl group, assisted internally by the attached imidazole group... 

Such nucleophilic displacements are likely to be addition-elimination reactions, whether or not radical anions are also interposed as intermediates. The addition of methoxide ion to 2-nitrofuran in methanol or dimethyl sulfoxide affords a deep red salt of the anion 69 PMR shows the 5-proton has the greatest upfield shift, the 3- and 4-protons remaining vinylic in type.18 7 The similar additions in the thiophene series are less complete, presumably because oxygen is relatively electronegative and the furan aromaticity relatively low. Additional electronegative substituents increase the rate of addition and a second nitro group makes it necessary to use stopped flow techniques of rate measurement.141 In contrast, one acyl group (benzoyl or carboxy) does not stabilize an addition product and seldom promotes nucleophilic substitution by weaker nucleophiles such as ammonia. Whereas... 

The nucleophilic displacement reactions of organolithium compounds with alkyl halides are second order insofar as the rates have been measured, but there are unexplained examples of autocatalysis and non-reproducable rate constants. The product of the reaction in the case of the methylallyl chlorides is the same mixture regardless of... 

Figure 27 shows plots of all the available EM s for closures of small- and common-sized saturated carbocycles and heterocycles by intramolecular nucleophilic displacement. Clearly, a-values as small as 0.1 would be required in order to calculate extrathermodynamically from (67) EM-values comparable to those actually observed for ring-sizes 3 and 4, and an even smaller value would be necessary for ring-size 5. This would lead to the conclusion that the effect of ring strain on cyclisation rates is insignificant. The same conclusion was recently drawn by Benedetti and Stirling (1983), based on rates and activation parameters for the cyclisation of bis-sulphonyl-stabilised carbanions to 3-, 4-, and 5-membered bis-sulphonylcyloalkanes. 

In accord with general Eyring TS theory, we may consider every elementary chemical reaction to be associated with a unique A- B supramolecular complex that dictates the reaction rate. In the present section we examine representative TS complexes from two well-known classes of chemical reactions Sn2 nucleophilic displacement reactions... 

In contrast with aliphatic nucleophilic substitution, nucleophilic displacement reactions on aromatic rings are relatively slow and require activation at the point of attack by electron-withdrawing substituents or heteroatoms, in the case of heteroaromatic systems. With non-activated aromatic systems, the reaction generally involves an elimination-addition mechanism. The addition of phase-transfer catalysts generally enhances the rate of these reactions. 

A phase-transfer catalysed nucleophilic displacement reaction on chloro-acetanilides by cyanate ions, followed by ring-closure (Scheme 5.10), provides a simple and viable synthesis of hydantoins [41], The formation of the hydantoins is inhibited by substituents in the orf/to-position of the aryl ring, but the addition of potassium iodide, or tetra-n-butylammonium iodide, generally increases the overall rate of formation of the cyclic compounds, presumably by facilitating the initial nucleophilic substitution step. 

---