Aminoacetal intermediate

The Pomeranz-Fritsch reaction involves the preparation of isoquinolines 4 via the acid-mediated cyclisation of the appropriate aminoacetal intermediate 3. The best yields are usually obtained when the benzaldehyde portion 1 has electron-donating substituents in the 3- or 3,4- positions relative to the aldehyde. 

Isoquinoline and saturated variants synthesis via acid-mediated cyclization of the appropriate aminoacetal intermediate. 

A variation involves the reaction of benzylamines with glyoxal hemiacetal (168). Cyclization of the intermediate (35) with sulfuric acid produces the same isoquinoline as that obtained from the Schiff base derived from an aromatic aldehyde and aminoacetal. This method has proved especially useful for the synthesis of 1-substituted isoquinolines. 

Alkylation of trifluoro- and trichloroacetamides with a-bromoacetic esters has been utilized for the synthesis of a wide range of a-aminoacetic acids [11-13] (Table 5.13). Hydrolysis of the intermediate a-trihaloacetamidoacetic esters with methanolic potassium hydroxide converts the methyl and ethyl esters directly into the amino carboxylic acids. /-Butyl a-aminoacetates are more stable, but they are hydrolysed under phase-transfer catalytic conditions (see Chapter 9.2). Reaction of the trihaloacetamides with 1,4-dibromobutane and 1,5-dibromopentane and subsequent hydrolysis provides a simple route to pyrrolidine-2-carboxylic acid (75%) and piperidine-2-carboxylic acid (58%) [11, 12],... 

Selected examples of the synthesis of a-aminoacetic acids via the intermediate trifluoroacetamido... 

Oxidation of sulphonamides in the presence of bromide or iodide ions and sodium methoxide in methanol also leads to formation of the N-halogeno intermediate. The nitrogen-halogen bond in these intermediates is weak and will undergo themiolysis. At -10 °C, reaction proceeds by base catalysed elimination of hydrogen halide and ftirther steps lead to an a-amino acetal 20. The reaction is carried out in an undivided cell and renders a-aminoacetals readily available for the iso-... 

The versatility of d,v-aminoindanol as chiral auxiliary has been considered in various Claisen9293 rearrangements and was found to be particularly efficient in the 6-azaelectrocyclization reaction.93 Indeed, the reaction of ( >3-carbonyl-2,4,6-trienal 98 with enantiopure m-aminoindanol 1 proceeded under remarkably mild conditions to produce pentacyclic piperidine 99 as a single isomer. The reaction was thought to proceed via isomerization of dihydropyridine intermediate 100 toward the thermodynamically more stable aminoacetal 99 (Scheme 24.22). 

The reaction of aminoacetic acid with carbon disulfide has been much studied especially in the presence of various alkylating agents. S-alkyl dithiocarbamates (CLXXXII) are formed as intermediates. These are then converted to the 2-(alkylthio)-z]2-thiazolin-5-one (CLXXXIII) by means of the classical dehydrating agents (224. ... 

A synthesis shown below of ethyl oxazole-4-carboxylate illustrates a sophisticated use of this strategy, in which an imino ether and the potassium enolate of an aldehyde are involved " iminoethers on reaction with aminoacetal give amidines, which close in acid to give 2-substituted imidazoles. " " The process can be conducted without isolation of the intermediate. 

The aromatic ring system has been prepared both from quinoxaline intermediates and from 1-phenylimidazoles. Reaction of the 2-chloroquinoxalines 1 with aminoacetaldehyde dimethylacetal followed by acid treatment of the resultant aminoacetals gave imidazo[l,2-ajquinoxaline (2) and its 4-phenyl derivative (3). Compound 3 was the... 

Bis(methylthio)nitroethene reacts with organocuprates, aryl or alkyl groups displacing one methylthio group. These products react with aminoacetal, as the a-aminocarbonyl synthon, to give intermediates which ring close to 2-substituted-3-nitropyrroles. ... 

Jackson modification and Schlittler-Muller modification. The Fischer modification involves the treatment of benzalaminoacetal with fuming sulfuric acid, whereas Bobbitt modification produces tetrahydroisoquinoline derivative through the hydrogenation of an imine intermediate in situ to an aminoacetal, which in turn is converted into product by the acid-promoted cyclization and hydrogenation. This modification for tetrahydroisoquinoline is also known as the Pomeranz-Fritsch-Bobbitt cyclization. The Schlittler-Muller modification involves the preparation of benzalaminoacetal from benzyl amines and gly-oxal semiacetal. In addition, this reaction has been extended to prepare other types of aromatic heterocycles, such as thieno[2,3-c] and thieno[3,2-c]pyridines by intromolecular cyclization to thiophene ring. ... 

Treating the protected amine 141 in the presence of the Rh-BIPHEPHOS catalyst (see Figure 3) under hydroformylation conditions, leads to enamide 142. The consecutive reactions are hydroformylation to give the linear aldehyde, cyclization to give aminoacetal and the elimination of water. Compound 142 is a key intermediate in the synthesis o rosopinine 143 [86]. 

---