Salt effects substitution

As has been noted above, there is no gross change in the mechanism of nitration of PhNH3+ down to 82 % sulphuric acid. The increase in o- andp-substitution at lower acidities has been attributed differential salt effects upon nitration at the individual positions. The two sets of partial rate factors quoted for PhNH3+ in table 9.3 show the effect of the substituent on the Gibbs function of activation at the m- and -positions to be roughly equal for reaction in 98 % sulphuric acid, and about 28 % greater at the -position in 82 % sulphuric acid. ... 

If (A i[X ]/A 2[Y ]) is not much smaller than unity, then as the substitution reaction proceeds, the increase in [X ] will increase the denominator of Eq. (8-65), slowing the reaction and causing deviation from simple first-order kinetics. This mass-law or common-ion effect is characteristic of an S l process, although, as already seen, it is not a necessary condition. The common-ion effect (also called external return) occurs only with the common ion and must be distinguished from a general kinetic salt effect, which will operate with any ion. An example is provided by the hydrolysis of triphenylmethyl chloride (trityl chloride) the addition of 0.01 M NaCl decreased the rate by fourfold. The solvolysis rate of diphenylmethyl chloride in 80% aqueous acetone was decreased by LiCl but increased by LiBr. ° The 5 2 mechanism will also yield first-order kinetics in a solvolysis reaction, but it should not be susceptible to a common-ion rate inhibition. 

A similar salt effect is observed in the reaction of propargylic epoxides67. RMgBr in diethyl ether in the presence of 5% CuBr PBu, gave an anti-SN2 substitution product, whereas RMgCl in diethyl ether/pentane in the presence of 5% copper(I) bromide and chlorotrimethylsilane (1 equivalent) afforded a syn-SN2 substitution product (Table 3). 

The kinetics of decarboxylation of 4-aminosalicylic acid in some buffer solutions at 50 °C were studied. The first-order rate coefficients increased with increasing buffer concentration, though the pH and ionic strength were held constant (Table 217). This was not a salt effect since the rate change produced by substituting potassium chloride for the buffer salt was shown to be much smaller. It follows from the change in the first-order rate coefficients (kx) with... 

Since the rate was independent of acidity even over the range where H0 and pH differ, and the concentration of free amine is inversely proportional to the acidity function it follows that the rate of substitution is proportional to h0. If the substitution rate was proportional to [H30+] then a decrease in rate by a factor of 17 should be observed on changing [H+] from 0.05 to 6.0. This was not observed and the discrepancy is not a salt effect since chloride ion had no effect. Thus the rate of proton transfer from the medium depends on the acidity function, yet the mechanism of the reaction (confirmed by the isotope effect studies) is A-SE2, so that again correlation of rate with acidity function is not a satisfactory criterion of the A-l mechanism. 

Nucleophilic aromatic substitution has been the subject of frequent and extensive reviews1-10. The data on reaction rates, reaction products, substituent effects, salt effects, etc. are all readily available and need not be reassembled here. In spite of this abundance of both data and discussion, some questions of mechanism remain incompletely resolved. 

A unimolecular ionization was shown to be the mechanism of solvolysis by means of rate studies, solvent effects, salt effects, and structural effects (179,180). The products of reaction consist of benzo [bjthiophen derivatives 209 or nucleophilic substitution products 210, depending upon the solvent system employed. By means of a series of elegant studies, Modena and co-workers have shown that the intermediate ion 208 can have either the open vinyl cation structure 208a or the cyclic thiirenium ion 208b, depending... 

Only low yields of the azide ion adduct are obtained from the reaction of simple tertiary derivatives in the presence of azide ion 2145 46 and it is not possible to rigorously determine the kinetic order of the reaction of azide ion, owing to uncertainties in the magnitude of specific salt effects on the rate constants for the solvolysis and elimination reactions. Therefore, these experiments do not distinguish between stepwise and concerted mechanisms for substitution reactions at tertiary carbon. 

An unusual solvent effect was observed in cycloadditions of aromatic nitrile N-oxides with alkyl-substituted p-benzoquinones in ethanol-water (60 40) the reaction rates were 14-fold greater than those in chloroform (148). The use of ion pairs to control nitrile oxide cycloadditions was demonstrated. A chiral auxiliary bearing an ionic group and an associated counterion provides enhanced selectivity in the cycloaddition the intramolecular salt effect controls the orientation of the... 

The difference between A obsd and caic might be due to a specific salt effect on the rate constant for solvolysis. However, this is unlikely because perchlorate ion acts to stabilize carbocations relative to neutral substrates.At high concentrations of sodium bromide, the rate-limiting step for solvolysis of 1-Br is the capture of 1 by solvent (ks Scheme 5A). Substitution of Br for CIO4 should destabilize the carbocation-like transition state for this step relative to the starting neutral substrate, and this would lead to a negative, rather than positive deviation of obsd for equations (3A) and (3B). 

K /Na exchange in distal tubule Dose Adults. 5-10 mg PO daily Peds. 0.625 mg/kg/d X in renal impair Caution [B, ] Contra T K, SCr >1.5 mg/dL, BUN >30 mg/dL, diabetic neuropathy Disp Tabs SE T K HA, dizziness, dehydration, impotence Interactions T Risk of hyperkalemia W/ ACEI, K-sparing diuretics, NSAIDs, K salt substitutes T effects OF Li, digoxin, antihypertensives, amantadine T risk of hypokalemia W/ licorice EMS Monitor ECG for signs of hyperkalemia (peaked T waves) T effects of digoxin OD May cause bradycardia, light-headedness, and syncope symptomatic and supportive... 

Hydrochlorothiazide A Spironolactone Aldactazide) [Antihypertensive/Thiazide K Sparing Diuretic] Uses Edema, HTN Action Thiazide K -sparing diuretic Dose 25-200 mg each component/d, doses Caution [D, +] Contra Sulfonamide aUa-gy Disp Tabs (HCTZ/spironolactone) 25 mg/25 mg, 50 mg/50 mg SE Photosens, X BP, t or -1-K% -1- Na% hypoglycemia, hyperlipidemia, hyperuricemia Additional Interactions t Risk of hypokalemia W/ ACEIs, K-sparing diuretics, K supls, salt substitutes -1- effects OF digoxin EMS See Hydrochlorothiazide Amiloride OD See Hydrochlorothiazide Amiloride... 

The yield of the nucleophilic substitution product from the stepwise preassociation mechanism k[ = k. Scheme 2.4) is small, because of the low concentration of the preassociation complex (Xas 0.7 M for the reaction of X-2-Y). Formally, the stepwise preassociation reaction is kinetically bimolecular, because both the nucleophile and the substrate are present in the rate-determining step ( j). In fact, these reactions are borderline between S l and Sn2 because the kinetic order with respect to the nucleophile cannot be rigorously determined. A small rate increase may be due to either formation of nucleophile adduct by bimolecular nucleophilic substitution or a positive specific salt effect, whUe a formally bhnole-cular reaction may appear unimolecular due to an offsetting negative specific salt effect on the reaction rate. 

A more satisfactory solution to the mechanism of these substitutions now seems experimentally feasible. It is likely that the trisamino chelate (XXXIII) could be completely resolved by salt formation with a suitable optically active acid. The optically pure amine could then be converted by electrophilic cleavage into optically active bromo-, chloro-, and thiocyanate-substituted chelates. It would thus be a simple matter to determine whether these substitutions proceed with complete retention of asymmetry. Further, the question of a symmetrical five-coordinate intermediate in racemization of such compounds could probably be elucidated by a study of solvent polarity or salt effects on the kinetics of the racemization of these chelates. 

The reactions of thiocyanogen may roughly be divided into two types (1) Reactions in which the radical combines directly with metals to form the corresponding thiocyanates, and with cuprous thiocyanate to form the cupric salt. (2) Reactions in which a substitution is effected for example, with aniline, dimethylaniline and phenol, the corresponding jj-thiocyano-derivatives and thiocyanie acid are formed.1... 

In the phenyl-substituted salts 45 and 46, the four-membered ring is found to be nearly planar with a relatively large distance between C(l) and C(3). The conformations of the phenyl groups on C( 1) and C(3) are such that they can effectively conjugate with the allylic system. 

Rubidium chloride even slows the reaction, this is especially well seen within a time span of 1-3 hr after the start of the process (Fig. 2, curve 2). In this case the normal salt effect is likely to prevail over the effect of oximate ion pair separation due to substitution of the potassium cation by the rubidium cation. The addition of cesium carbonate during the first 1.5 hr does not much affect the rate of the formation of 2-phenylpyrrole. The accelerating effect of these additives becomes evident only 2 hr after the beginning of the reaction and gradually increases (5 hr later the yield gain of pyrrole is 7% as compared with a standard run, Fig. 2, curve 4) which seems to result from a slow rate of heterophase exchange process ... 

A study19 of the effect of added lithium perchlorate on the second-order rate coefficients for reaction (12) (R = Et, Pr", Bu") showed that all three substitutions, in solvent 96 % methanol-4 % water, were subject to marked positive kinetic salt effects. The effects were analysed in terms of the Bronsted-Bjerrum equation... 

Fig. 1. Kinetic salt effects in the bimolecular substitution of tetraalkyltins (R4Sn) by mercuric iodide in solvent 96 % methanol-4 % water. Et = Et4Sn, Pr" - Pr4"Sn, Bu — Bu"4Sn.

---