Morpholine, proton transfer

Since morpholine and piperidine are stereochemically similar but exhibit different pKa values, the difference between their rates in the reactions of the fluoro-substrates in acetonitrile could be also due to a change in mechanism, whereby proton transfer from the intermediate 1 in equation 1 becomes rate-limiting when the reagent is morpholine. The change from an uncatalysed to a base-catalysed reaction with decrease in basicity of the nucleophile is well known in ANS for both primary and secondary amines1 200. 

A related asymmetric dimerization is seen in the aminophosphinite-Ni(0) catalyzed dimerization of conjugated dienes (Scheme 61) 133). 1,3-Pentadiene forms head-to-head linked optically active 1,3,6-trienes that subsequently are isomerized to achiral 2,4,6-trienes. The linear dimerization is considered to proceed via a bis-ir-allylnickel intermediate, where the NH group in the ligand mediates proton transfer in the reaction. The reaction rate is one to two orders of magnitude higher than the reaction using morpholine, ethanol, or P-methyloxaphospholidines as modifiers. 

To test further the hypothesis that proton transfer from cyanocarbon acids is approaching normal behaviour, measurements were made [19] around ApK ca. 0 by studying the ionization of bromomalononitrile (pK° 7.81) in phosphate (pK° 7.21) and morpholine (pK° 8.49) buffers using the temperature-jump technique. The results of these experiments... 

Fig. 5. Rates of proton transfer for cyanocarbon acids. Open and closed points represent forward (log10 k, ) and reverse (logI0 -i ) rate coefficients, respectively, and ApK is the statistically corrected difference in acidities between the cyanocarbon acid and base (B). Points are o and for f-butylmalononitrile reacting with carboxylate ions and H20 a and for malononitrile with formate ion and H20 and for bromomalononitrile with phosphate ion and morpholine x for 1,4-dicyano-2-butene with phenolate ions. Redrawn with permission from F. Hibbert and F. A. Long, J. Am. Chem. Soc., 94 (1972) 2647. Copyright by the American Chemical Society.

The color change is observed only in protic solvents, demonstrating the participation of the solvent during the proton transfer occurring before the morpholine elimination. Solutions of 250 are uncolored when dissolved and become yellow when thermal equilibrium is established. Depending on the... 

Kinetic studies of Michael addition of alicyclic secondary amines to ethyl propiolate in H2O and MeCN have demonstrated a substantial solvent effect on reactivity and transition-state structure. The amines were found to be less reactive in MeCN, although they are by 7-9 units more basic in the aprotic solvent. The reaction rates for morpholine and deuterated morpholine proved to be identical, which rules out both a stepwise mechanism in which proton transfer would occur in the RLS and a concerted mechanism in which nucleophilic attack and proton transfer would occur through a four-membered cyclic transition state. Consequently, a stepwise mechanism with proton transfer occurring after the RLS is probable. Br0nsted-type plots were found to be linear with = 0.29 and 0.51 in H2O and MeCN, respectively, indicating that bond formation is not advanced significantly in the RLS. The small value is also consistent with the absence of isotope effect. ... 

Abstract. Nucleophilic addition of amines to olefins which are activated by electron withdrawing substituents occurs readily in aqueous dimethylsulfoxide. The reaction comprises two steps (1) nucleophilic addition to form a zwitterionic complex (2) removal of the ammonio proton of the zwitterion by a base. In most cases the first step is rate limiting but in some cases proton transfer is rate limiting. The latter situation prevails either when the reverse of the nucleophilic attack step is very rapid, as in the reaction of morpholine with benzylidenemalononitrile, or when the rate of proton transfer is depressed by a steric effect, as in the reaction of morpho-line with 1,l-dinitro-2,2-diphenylethylene. The steric effects in this latter system are among the most dramatic ones reported to date. Our data also show that the kinetic barrier to nucleophilic attack is substantially higher for nitro than for cyano activated olefins. This effect seems to be related to the well known fact that proton transfers involving nitro activated carbon acids are much slower than those of cyano activated carbon acids. 

Behavior according to Fig. 2 shows a transition from rate limiting proton transfer at low amine concentration to rate limiting nucleophilic attack at high amine concentration. This comes about because the k2p[RR NH] term in eq 3 is dominant and thus k2p changes from k2p < k -j at low to k2p >> k j at high amine concentration. This behavior is exemplified by the reactions of 2 with morpholine and aniline (5), and by the reaction of 3 with morpholine (7). 

On the other hand, in the reaction of morpholine with 2 = 2.4 X 10 sec" is relatively low here it is the unusually low proton transfer rate constants (entries 6-9 in Table II) which make k2p < reasons for the slow proton... 

A selection of proton transfer rate constants is summarized in Table II. Our results for the 2/morpholine system are particularly striking. All rate constants refer to thermodynamically strongly favored (ApK >> 0) proton transfers between normal acids and bases and thus would be expected to have values in the order of 10 to 10 s " ( v Iq for T + (3). However the... 

Line I filled squares proton transfer from (EtS02)2 CHMe to a series of oxyanions. Data from Reference 26. Filled circles proton transfer from tert. butyl malononitrile to a series of oxyanions. Data from Reference 28. Open squares proton transfer from malononitrile to morpholine, phosphate and bicarbonate. Data from Reference 28. Open circle proton transfer from 1,4-dicyanobutene to a series of amines. Data from Reference 28. Open triangles proton transfer from a series of disulphones to H2O. Data from Reference 27. 

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