Hydrolysis imines

A -1,3,4-Oxadiazolin-2-imine, N-phenyl-pyrolysis, 6, 437 A -1,3,4-Oxadiazolin-5-imines IR spectra, 6, 429 A -1,3,4-Oxadiazolin-2-imines hydrolysis, 6, 438... 

The transaldolase functions primarily to make a useful glycolytic substrate from the sedoheptulose-7-phosphate produced by the first transketolase reaction. This reaction (Figure 23.35) is quite similar to the aldolase reaction of glycolysis, involving formation of a Schiff base intermediate between the sedohep-tulose-7-phosphate and an active-site lysine residue (Figure 23.36). Elimination of the erythrose-4-phosphate product leaves an enamine of dihydroxyacetone, which remains stable at the active site (without imine hydrolysis) until the other substrate comes into position. Attack of the enamine carbanion at the carbonyl carbon of glyceraldehyde-3-phosphate is followed by hydrolysis of the Schiff base (imine) to yield the product fructose-6-phosphate. 

Both monohydrido complexes contain a cyclometalated molecule derived from the N-benzylideneaniline substrate, and the presence of the aniUne Ugand in the later complex seems to be due to some imine hydrolysis caused by adventitious water. Accordingly, this aniline complex practically disappears when carefully dried substrates and solvents are used [29]. 

In contrast, 2-methylcyclohexanone and 2-methylindanone were racemized during imine hydrolysis with sodium acetate/acetic acid/pentanc/water8. In the preparation of 2-isopropyIcy-clohexanone and 2-isopropyl-6-methylcyclohexanone enantiomeric excess of the final products was low due to racemization8. 

The effect of metal ions on the hydrolysis of imines is of considerable biological interest. A number of papers have discussed the effect of metal ions on the formation and hydrolysis of such compounds.389-400 Until recently detailed kinetic studies on imine hydrolysis were lacking, but a number of detailed investigations have now been carried out. The low solubility of many aromatic imines (which are generally more readily characterized) in aqueous solution has led to the use of mixed alcohol-water solvent systems which can lead to problems of interpretation. 

The reductive alkylation of methyl pyruvate with and the t-butyl esters of amino acids using Pd/C catalyst leads to the formation of iminodicarboxylic acids such as 67 in selectivities of 29-75% d.e. depending on the amino acid and solvent used (hexane gave the best results). Hydrolysis of the t-butyl ester to the acid 68 followed by hypochlorite-promoted decarboxylation and imine hydrolysis leads to the formation of ( -alanine 69 in correspondingly high e.e.s278,281. The likely decarboxylation mechanism as far as the imine stage is shown in Scheme 65. 

The catalytic and chiral efficiency of (S,S)-le was also appreciated in the asymmetric synthesis of isoquinoline derivatives, which are important conformationally constrained a-amino acids. Treatment of 2 with a,a -dibromo-o-xylene under liquid-liquid phase-transfer conditions in the presence of (S,S)-le showed complete consumption ofthe starting Schiffbase. Imine hydrolysis and subsequent treatment with an excess amount of NaHCOs facilitated intramolecular ring closure to give 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid tert-butyl ester 38 in 82% yield with 98% ee. A variety of l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives possessing different aromatic substituents, such as 39 and 40, can be conveniently prepared in a similar manner, with excellent enantioselectivity (Scheme 5.20) [25]. 

Other API examples include methaqualone (87) and terbutaline sulfate in which the amine converts to an imine followed by imine hydrolysis (88). In the case of diazepam under acidic aqueous conditions, the imine undergoes hydrolysis to the corresponding benzophenone (Fig. 54) (89). 

In the case of xylometazoline hydrochloride, imine hydrolysis chemistry occurs to open the 4,5-dihydro-lH-imidazole ring (Fig. 55) (90). Similar degradation chemistry is observed for the following APIs flurazepam hydrochloride (91), clorazepate dipotassium (92), clonazepam (93), methaqualone (94), chlordiazepoxide, and oxazepam (18). 

A similar approach was reported by Lygo and co-workers who applied comparable anthracenylmethyl-based ammonium salts of type 26 in combination with 50% aqueous potassium hydroxide as a basic system at room temperature [26, 27a], Under these conditions the required O-alkylation at the alkaloid catalyst s hydroxyl group occurs in situ. The enantioselective alkylation reactions proceeded with somewhat lower enantioselectivity (up to 91% ee) compared with the results obtained with the Corey catalyst 25. The overall yields of esters of type 27 (obtained after imine hydrolysis) were in the range 40 to 86% [26]. A selected example is shown in Scheme 3.7. Because the pseudo-enantiomeric catalyst pairs 25 and 26 led to opposite enantiomers with comparable enantioselectivity, this procedure enables convenient access to both enantiomers. Recently, the Lygo group reported an in situ-preparation of the alkaloid-based phase transfer catalyst [27b] as well as the application of a new, highly effective phase-transfer catalyst derived from a-methyl-naphthylamine, which was found by screening of a catalyst library [27c],... 

In the case of 269a along with 272a, the reduction produced the intermediate amine 271a, as main product (56%). The presence of the intermediate was independent on the reduction time but rather resulted by an imine hydrolysis promoted by the aqueous acidic medium (Scheme 49) <2005SC1493>. 

Reduction of the nitrile with H2 and Pd-BaS04, a poisoned Pd catalyst, forms an imine. Hydrolysis of the imine with aqueous acid forms an aldehyde that has one more carbon than the aldose that began the sequence. 

Imines can be hydrolyzed in quantitative yield by use of boric acid in ethanol under reflux [1]. Imines that are susceptible to intra- and intermolecular attack in the presence of other catalysts have been successfully hydrolyzed by use of boric acid [2], The conversion of isoxazolines into y3-hydroxy ketones and yS-hydroxy esters involves hydrogenolysis of the N-O bond and imine hydrolysis in a single step [3]. In the presence of boric acid, racemization is inhibited (Eq. 1) [3a]. 

Mukaiyama and coworkers have pioneered many routes to the total syntheses of rare carbohydrates such as the 2-amino-2-deoxypentoses [75]. In 1982, they reported that the potassium enolate derived from the magnesium salt of the (/ )-atrolactic acid derivative 85 adds to 2,3-0-isopropylidene-D-glyceraldehyde in a highly stereoselective manner giving, after alcohol protection, imine hydrolysis and amine protection, the D-arabinopentoate derivative 86 (Scheme 13.35). Further elaboration leads to 2-acetamido-2-deoxy-D-arabinose 87. In a similar fashion, starting from (5 )-atrolactic acid, 2-acetamido-2-deoxy-D-ribose 88 was prepared [76]. 

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