12256-88-1

Upstream product

• 110-91-8 morpholine 
• 1214-54-6 5-benzylidene Meldrum's acid 

Downstream Products

• 28627-67-0 succinimide anion 
• 135346-51-9 Acetic acid (1S,2S,5R,6S)-5,6-diacetoxy-2-(2,2-dimethyl-4,6-dioxo-[1,3]dioxan-5-yl)-cyclohex-3-enyl ester 

Relevant academic research and scientific papers

Kinetic Solvent Isotope Effect and Proton Inventory Study of the Carbon Protonation of Amine Adducts of Benzylidene Meldrum's Acid and Other Meldrum's Acid Derivatives. Evidence for Concerted Intramolucular Proton Transfer

Rate constants for carbon protonation of the glycinamide and morpholine adducts of benzylidene Meldrum's acid (TA-(gly) and TA-(mor)) and of the anions of 5-benzyl and 5-(1-phenylethyl) Meldrum's acid (13 and 14) were determined in H2O and D2O.For protonation by L3O+ the kinetic solvent isotope effects for TA-(gly) and TA-(mor) are very low (0.82 and 0.72 respectively) and about threefold lower than those of 13 (2.48) and 14 (2.52); for protonation by L3+NCH2CONH2 the isotope effects are all normal, i.e., 6.01 for TA-(gly), 6.57 for 13, and 7.68 for 14.It is shown that the unusually low isotope effects for protonation of TA-(gly) and TA-(mor) by L3O+ are the result of a two-step mechanism which involves equilibrium protonation on the amine nitrogen, followed by rate limiting intramolecular proton switch from nitrogen to carbon.On the basis of this mechanism one may calculate a kinetic isotope effect for the intramolecular proton switch step of 3.66 (TA-(gly)) and 3.29 (TA-(mor)), respectively.Plausible alternative mechanisms such as carbon protonation by L3O+ with transition-state stabilization by hydrogen bonding between the amine nitrogen and L3O+, or preequilibrium protonation on the amine nitrogen followed by rate-limiting carbon protonation by water, with transition-state stabilization by hydrogen bonding between the protonated amine nitrogen and the incipient hydroxide ion, are not consistent with the data.A proton inventory on the intramolecular proton switch step shows that the transition state includes a water molecule that acts as a bridge for the proton transfer.On the other hand, the proton inventory on the intermolecular protonation of TA-(gly) by L3+NCH2CONH2 indicates that the proton transfer is direct, in agreement with prevailing views.

Nucleophilic Addition to Olefins. 4. Structure-Reactivity Relationships in the Reactions of Amines with Substituted Benzylidene Meldrum's Acids. Evidence for Intramolecular Proton Transfer to Carbon

The reactions of piperidine and morpholine with benzylidene Meldrum's acid (1-H) and its p-OMe and p-NMe2 derivatives (1-OMe, 1-NMe2) in water are characterized by a fast and slow kinetic process.The fast reaction refers to the formation of a zwitterionic adduct (TA+/-) which is in rapid acid-base equilibrtium with TA- (eq 1).The slow process leads, via an iminium ion, to the respective benzaldehyde and Meldrum's acid anion (eq 3) whereby protonation of TA- on carbon, to form TA0, is rate limiting.The effect of the substituents in the olefin on rate (K1) and equilibrium constants (K1) for adduct formation indicate that the transition state is located approximately halfway between reactants and products (δ log K1/δ log K1 = 0.40 - 0.45).On the other hand, βnuc is extremely low (0.07 -0.12), suggesting that C-N bond formation has made very little progress in the transition state.These data then suggest an imbalanced transition state for which two different and possibly complementary explanations are proposed.According to the first, rehybridization of the benzylic carbon (site of nucleophlic attack) is ahead of C-N bond formation.In the second it is assumed that some negative charge is localized on the benzylic carbon in the transition state but delocalized into the (COO)2C(CH3)2 moiety in the product, as has been suggested for the nitroalkane anomaly.Prhotonation of TA- on carbon by morpholinium ion is retarded 1000-fold owing to a steric effect; carbon protonation by the hydronium ion occurs mainly by prior equilibrium protonation on nitrogen, to form TA+/-, followed by an intramolecular proton switch, TA+/- -> TA0 (eq 3), through an intermediate water molecule.