From Aminoaldehydes

This synthesis was first described by Bischler, who, in 1891, prepared 2-methylquinazoline by heating 2-acetamidobenzaldehyde (81) with ethanolic ammonia at 100oC. ° It is now known that the reaction proceeds excellently at room temperature, being complete in 18 hr (in even less time when the acyl group is more electron attracting).81 Precautions to avoid polymerization of 2-aminobenzaldehyde when it is being acylated have been worked out.81 

An alternative approach, when the appropriate 2-nitrobenzaldehyde is available, is Riedel s synthesis82 dry hydrogen chloride was passed through a suspension of the aldehyde in formamide to give (82), which was reduced 

The rarity of 1,2-dihydroquinazolines lends interest to the preparation of 3-methyl- 1,2-dihydroquinazolinium (83), isolated as its picrate, from a mixture of 2-aminobenzaldehyde, formaldehyde, and methylamine set aside at 20°C at pH 5 for 3 days (excellent yield).84 

In the still more 7t-deficient 1,2,3-triazole series (see 20), several 4-amino-5-formyl derivatives resisted both direct acylation and acetal formation. A successful alternative was to form intermediates with side chains conjugated to the nucleus. For example, 1- and 2-methyl-, as well as 3-benzyl-4-amino-l,2,3-triazole-5-aldehydes reacted with a cold mixture of dimethylformamide and phosphoryl chloride to give excellent yields of, e.g., 3-benzyl-4-dimethyl-aminomethyleneamino-l,2,3-triazole-5-aldehyde (84). This was converted to 9-benzyl-8-azapurine (see 21) in excellent yield by refluxing in methanolic ammonium acetate.87 In a variation of this reaction, an imidate (85) replaced the amidine (84) as intermediate. Thus, 4-amino-l-methyl-l,2,3-triazole-5-aldehyde and triethyl orthoacetate, refluxed for 2 hr, gave an excellent yield of 4-ethoxyethylideneamino-l,2,3-triazole-5-aldehyde (85), cyclized, by stirring in cold ethanolic ammonia, to 2,7-dimethyl-8-azapurine (good yield).87 

In an extension of these reactions, 4-amino-2-methyl-l,2,3-triazole-5-aldehyde was refluxed with tetraethyl orthocarbonate. The isolated intermediate (86), stirred with cold ethanolic ammonia, provided 2-ethoxy-8-methyl-8-azapurine in good yield.87 This reaction seems to be unique for producing a 2-alkoxy-substituted pyrimidine ring. 

---

Espelt, L., Parella, T., Bujons, J., Solans, C., Joglar, J., Delgado, A. and, Clapes, P., Stereoselective aldol additions catalyzed hy dihydroxyacetone phosphate-dependent aldolases in emulsion systems preparation and structural characterization of linear and cyclic iminopolyols from aminoaldehydes. Chem. Eur. J., 2003, 9, 4887. 

Cyclic Schiff bases derived from aminoaldehydes or aminoketones ... 

Cyclic Schiff bases from aminoaldehydes and aminoketones... 

The parent compounds undergo facile hydrolysis to aminoaldehydes subsequent to the covalent hydration and reversible ring-opening as described above for pyrido[4,3-d]pjrrimidines (Section IV, B). 2-(3-Pyridyl)pyTido[2,3-d]pyrimidine undergoes hydrolysis to yield 2-aminonicotinaldehyde and nicotinamide when treated with N—HCl under reflux for 3 hours. This mechanism also probably involves a covalent hydrate. 2-Methylpyrido[4,3-d]pyrimidin-4(3H)-one, although much more stable than the parent compound, is readily hydrolyzed with dilute acid, whereas the isomeric compounds from the other three systems are stable under such conditions. 

Our efforts to concretely determine the relative stereochemistry of this dimer have been met by failure. We have made attempts to resolve several of the monomeric tetracyclic aminoaldehydes of type 100 by HPLC using chiral stationary phase, in order to know for sure the structure of the homodimer. The poor solubility of these compounds in typical HPLC solvents hampered these efforts to access enantiopure monomer. A few attempts at diastereomeric salt formation from compounds of type 101 using chiral carboxylic acids were also unsuccessful. Computational analysis corroborates the assumption that the homodimer should be formed preferentially. 

A stereochemical behavior similar to that of the 1-bromo-l-lithio aUcene 164 with regard to chiral aldehydes is shown by the hthiated methoxyallene 183. When added to iV,iV-dibenzylated a-aminoaldehydes 188, it reacts with non-chelate control so that awh -carbinols 189 are obtained predominantly. Diastereomeric ratios of 189 190 range from 80 20 to 95 5. As outlined above, the hydroxyalkylated allenes 189/190 can be converted into furanones 191/192 upon treatment with potassium f-butoxide and subsequent acid hydrolysis" . When, on the other hand, the adducts of 183 to the aldehydes 193 are submitted to an ozonolysis, A-protected a-hydroxy-/3-amino esters 194/195 result (Scheme 25)"" . 

In a similar way to the formation of 273 from 272, the 3-hydroxytetrahydrooxazine 218 was prepared from the 3-oxa-5-aminoaldehyde diethyl acetal 275 in 60% yield using oxalic acid to bring about the cyclization (Equation 24) <1981JHC825>. 

At low temperatures, the Zn enolate derived from dimethyl 3-methylpent-2-endioate 39 reacts with aldehydes in a one-pot aldolisation and cyclisation to yield the syn-dihydropyran-2-one 40. At the higher temperatures necessary to achieve reaction with a-aminoaldehydes, the anri-products predominate indicating thermodynamic control (Scheme 22) <99T7847>. An aldol condensation features in the asymmetric synthesis of phomalactone. The key step is the reaction of the enolate of the vinylogous urethane 41 with crotonaldehyde which occurs with 99% syn-diastereoselectivity and in 99% ee (Scheme 23) <99TL1257>. 

Imines 223 derived from glyoxal acetals react with various organomagnesium compounds with high diastereoselectivity (equation 152) . The 1,2-aminoalcohols 224 can be converted into the protected enantiopure aminoaldehydes 225. For these reactions toluene was found to be a superior solvent. 

In the first step, the tertiary amide structure is reduced to hemiaminal 31 with the aid of the at complex (30) from D1BAH and butyl-lithium The hemiaminal opens selectively to aminoaldehyde 32 In a second step the ring nitrogen atom is protected as carbamate 11 with ethyl ehloroformate. 

A-Boc-cr-aminoaldehyde condensation products 78 are also precursors for nucleophilic attack via an internal nucleophile onto the carbonyl derived from the carboxylic acid of the classical Ugi adduct in an acid-catalyzed process. Thus, reaction in the Ugi followed by TFA treatment and prolonged evaporation in a Savant or GeneVac evaporator (8 h) affords imidazolines 79 containing four potential points of diversity in good... 

---