Methylamine, reaction with phthalimides

Theil et al. developed a method for chemoenzymatic synthesis of both enantiomers of cispentacin [89]. frans-2-Hydroxymethylcyclopentanol, obtained by the sodium borohydride reduction of ethyl 2-oxocyclopentanecarboxylate, was monosilylated with tert-butyldimethylsilyl (TBDMS) chloride to afford 55. Lipase PS-catalysed transesterification with vinyl acetate in /erf-butyl methyl ether furnished the ester 56 and the alcohol 57. The deacetylated 58 was obtained by the Mitsunobu reaction with phthalimide, triphenylphosphine and diethyl azodicarboxylate (DEAD) to furnish the cis oriented 59 with inversion of configuration (not retention as mentioned in the original article) (Scheme 9). Desilylation, Jones oxidation and subsequent deprotection with aqueous methylamine gave the ( R,2S) enantiomer 5 [89]. The (15, 2/f) enantiomer was prepared by the same route from the silyl alcohol 57. 

Allylic amines. With phthalimide reaction, high yields of the AJ-allylated phtht be removed with methylamine in methanol... 

A different approach using alkene derivatives involved allylic substitution reactions. Ethyl cyclohex-3-en-l-carboxylate (7.51) reacted with N-bromosuccin-imide to give 7.52.26 This allowed reaction with potassium phthalimide to give 7.53 in an overall yield of 41%. Catalytic hydrogenation and treatment with methylamine led to ds-3-aminocyclohexane-l-carboxylic acid, 7.22.26... 

The observed kinetic data summarized in Table 7.1 and Table 7.2 follow the simple first-order rate law for less than nine half-lives of the reactions. However, the observed kinetic data for the reaction of methylamine with phthalimide at 0.08-M CH3NH2 buffer of pH 10.93 do not follow strictly a first-order rate law if the data analysis includes all the observed data points within observed t range 20 to 2220 sec, as is evident from the A,.a. <, values in Table 7.3. But, the rate of methylaminolysis of phthalimide follows the first-order rate law for the reaction period of < 10 half-lives, as is evident from the data analysis shown in Table 7.3. Similarly, the rate of 2-hydroxyethylaminolysis of phthalimide at 0.20-M2-hydroxyethylamine buffer of pH 9.84 follows the first-order rate law for the reaction period of < 3.5 half-lives. The chemical reasons for the deviation of observed data points from the first-order rate law in these reactions are described in detail elsewhere."... 

In case the value of A cannot be obtained with certainty, the classical Guggenheim method can be used to overcome this problem. But the Guggenheim method also suffers from a serious limitation, i.e., it must be certain that the reaction obeys the first-order rate law until t = °o (i.e., the reaction time at which Aobs = A J. Thus, this method may yield an erroneous value of k if it is used for the reactions of primary amines, such as methylamine, with phthalimide. However, the observed kinetic data for such reactions may be easily and relatively accurately analyzed by the iterative method (Table 7.3) rather than other conventional approaches and the Guggenheim method. 

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