Propiolactone, hydrolysis

A mixture of 100 g (0.6 mole) of 1-morpholino-l-cyclohexene, 28.8 g (0,4 mole) of /3-propiolactone, and 100 ml of chlorobenzene is placed in a 500-ml round-bottom flask fitted with a condenser (drying tube). The mixture is refluxed for 4 hours. The solvent and excess enamine are removed by distillation at aspirator pressure. (The residue may be distilled to afford the pure morpholide, bp 187-18871 rnm, 1.5090.) Basic hydrolysis may be carried out on the undistilled morpholide. To the crude amide is added 400 ml of 10% sodium hydroxide solution. The mixture is cautiously brought to reflux, and refluxing is continued for 2 hours. The cooled reaction mixture is made acidic (pH 4) and is extracted three times with ether. The combined ether extracts are washed twice with 5 % hydrochloric acid solution and twice with water. The ethereal solution is dried (sodium sulfate), then filtered, and the solvent is removed (rotary evaporator). The residue may be recrystallized from petroleum ether-benzene, mp 64°. 

Exercise 18-26 What can you conclude about the mechanism of acid-catalyzed hydrolysis of oxacyclobutan-2-one (/8-propiolactone) from the following equation ... 

The acidity function has been used in analyzing the kinetic data on acid-catalyzed reactions in concentrated solutions. Longhand Purchase found that the rate of hydrolysis of /S-propiolactone in concentrated aqueous solutions of H2SO4 and HCIO4 is first-order in lactone and proportional to ho. The over-all reaction is... 

When deviations do occur from the ho relation and they are not directly traceable to the activity coefficient assumption, then it may be taken as evidence for a mechanism that does not involve simple decomposition of the conjugate acid of the substrate. Such is the case, interestingly enough, in the closely related, acid-catalyzed hydrolysis of 7-butyrolactone, which has been very carefully studied in HCIO4 and HCl solutions.- To account for the fact that the catalyzed reaction rate was proportional not to ho but instead to (H" "), the authors have proposed a mechanism very similar to that for the jS-propiolactone [Eq. (XVI.5.9)]... 

The value of AV = +2.5 cm3 found for the acid catalyzed hydrolysis of (3-propiolactone (Table 2) confirms the A1 mechanism [43], Furthermore, it also excludes transition state model I which involves partial charge separation and a negative contribution to AF due to electro-striction of the solvent. 

The uiechauism of the hydrolysis has also been confirmed by n kinetic study carried out with i>ropic1actono and the iactone.H i>l 3-hydroxyhutyric acid - (Fig. 7) and malic acid, - flit-hydrogen ion conoentratiou ueoesaary for mechanism Aac w imn-h higher with propiolactone than with the /3-methyl homolog. 

For the preparation of a, -dlpheiiyl-j9-propiolactone, whifdi is completely insoluble in water and therefore dues not undeigo hydrolysis [reaction (III)], the jS-chloro acid gives the highest yidd< [Pg.334]

Joos B has reported that ointments centaming 0.1-0.4% of a Tuixture of propiolactone and aqueous albumin 30%) gi-ve excellent cosmetic results with regeneration of the skin. However, if one grants that Complete hydrolysis does not occur rapidly, there are objections to its cosmetic application in vitro propiolactone destroys certain enzymes of skin samples stored for use as grafts ° it is a vesicant (seotkm IX.l..d) and in addition osjtnnogenk. It initiates epitheliomas in rats when iq lied locally. 

Long and his co-workers (Long, Dunkle, and McDevit, 75) have used the acidity function to decide whether or not a water molecule is present in the activated complex in the acid-catalyzed hydrolysis of 7-butyro-lactone. They found no correlation with Ho and therefore conclude that the water molecule is present in the activated complex. This is in contrast to their findings for the hydrolysis of /S-propiolactone. Paul (76) has studied the decomposition of trioxane in mixtures of perchloric acid and sodium perchlorate at constant perchlorate concentration (6 M) and found good correlation with the acidity function as determined by Harbottle (77). 

The synthesis of various phosphonate analogues of aspartic acid, glutamic acid and their homologues and serine phosphate have been reported. The kynurenine phosphinic acid analogue 217 and the corresponding phosphinate 218 have been synthesised from iV-protected 2-amino P-propiolactone (Scheme 27). Kinetic resolution was achieved by esterase-selective hydrolysis of the carboxylate group in the diester. 

Dialkylaluminum acetylides add smoothly to 6-propiolactones [(78) R=H, Me] giving the acids (79) in 38-95% yields.6 Kinetic resolution of racemic allenic esters has been effected by partial hydrolysis (31-50% conversion) using PLE (Scheme 3).67 Optical yields are best (up to 93% ) with highly substituted substrates. 

Questions about the gross mechanism that remain to be answered are whether the proton in the reactive protonated ester is on the carbonyl oxygen or on the ether oxygen, whether the attacking water molecule first adds or substitutes directly, and whether or not the transition state is highly polar. These questions are similar to those discussed earlier in connection with the hydrolysis of 8-propiolactone, and the possible transition states are similar to those in Table 7. Again, of course, the representations are of extreme transition states, and the true one may be intermediate. A decision in favor of one of these representations is to be taken as an abbreviated statement, the fuller description being that the particular transition state chosen is nearer the true one than any other. 

The acid-catalysed, neutral, and base-catalysed hydrolysis of seven lactones was studied using a hybrid supermolecule polarizable continuum model (PCM) approach including six explicit water molecules. DFT and ab initio methods were used to analyse the features of the various possible hydrolysis mechanisms of -propiolactone, j0-butyrolactone, j0-isovalerolactone, diketene, y-butyrolactone, 2(5//)-furanone, and... 

The mechanisms of the regioselectivity and stereochemistry of the ring-opening reactions of y3-butyrolactones by activated anions has been reviewed. A study of the mechanism of hydrolysis of y3-propiolactone has been reported. A mechanistic appraisal of diastereoselective and enantioselective syntheses of optically active j8-lactones has been made. An ab initio study on the thermal decomposition of y-butyrolactone has shown that decarbonylation is easier energetically than decarboxylation. ... 

Hydrolysis of -propiolactone in concentrated perchloric acid solution [8]... 

Specific features of the mechanism the reaction occurs in die absence of acid its rate is independent of pH in some interval of its change. Oxygen fiom water transits to alcohols (experiments in water enriched in 0). If the a-C atom of the alcohol residue is asymmetric, the inversion of the optical activity occurs during t drolysis. Steric effect also influences the reaction rate. This mechanism was established for lactone hydrolysis b-propiolactone, p-butyrolactone, and lactone of malic acid. 

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