Aldehyde-ammonia adducts

The aldehyde-ammonia adducts usually are not very stable. They readily undergo dehydration and polymerization. 1-Aminoethanol, for example, gives a cyclic trimer of composition C6Hl5N3-3H20, mp 97°, with structure 4 ... 

This reaction can be used for the detection of aldehydes in the presence of ketones and for the differentiation of aliphatic aldehydes from aromatic ones. In a neutral medium aldehydes produce a black color or a precipitate other transient colors are sometimes formed which, in the case of aromatic aldehydes, last a bit longer. In an acid medium aliphatic aldehydes behave similarly as in a neutral medium, while in the presence of aromatic aldehydes a yellow color is produced first sometimes a precipitate is formed which persists for a certain time. Some other derivatives also react similarly to aide-hydes, such as, for example, cyanohydrins, aldehyde-ammonia adducts, sodium bisulfite addition compounds of aldehydes, and oximes. For modification with detection tubes containing the reagent see (62). 

Chloral forms well-crystallized adducts (126) with diaziridines containing at least one NH group (B-67MI50800). Carbonyl addition products to formaldehyde or cyclohexanone were also described. Mixtures of aldehydes and ammonia react with unsubstituted diaziridines with formation of a triazolidine ring (128). Fused diaziridines like (128) are always obtained in ring synthesis of diaziridines (127) from aldehyde, ammonia and chloramine. The existence of three stereoisomers of compounds (128) was demonstrated (76JOC3221). Diaziridines form Mannich bases with morpholine and formaldehyde (64JMC626), e.g. (129). 

Ammonia itself yields imines, R2C=NH, with carbonyl compounds but these derivatives are unstable and react with each other to form polymers of varying size. The classical aldehyde ammonias are found to be hydrated cyclic trimers, but from aldehydes carrying powerfully electron-withdrawing substituents it is possible to isolate the simple ammonia adduct [73, cf. (72), and hydrates, p. 208, hemi-acetals,... 

We found that if 2 equivalents of ethyl 4,4,4-trifluoroacetoacetate (ETFAA) were reacted with one equivalent of an aldehyde and ammonium hydroxide in ethanol under the standard Hantzsch dihydropyridine synthesis conditions, a cis-dihydroxypiperidine 8a was obtained in modest yields after recrystallization. By carefully monitoring the crude reaction mixture with nmr, we were able to identify one of the other products as the trans isomer 8b which is usually more soluble and remains in the mother liquor. The other remaining products were identified as the ammonium salt, enamine, and possibly hydrate, ammonia adduct and hemiketal of ETFAA. We found that better results were obtained if 2 equivalents of ETFAA were reacted with one equivalent of an aldehyde first in a nonprotic solvent followed by passing excess gaseous ammonia into the reaction mixture to form a mixture of cis - and trans-2,6-dihydroxypiperidines 8a and 8b. The nmr shows that, in this manner, the combined yields of cis- and trans-2.6-dihydroxypiperidines 8a and 8b are in excess of 90%. The nmr spectrum also reveals that an isomeric mixture of 2-... 

With aldehydes some diaziridines condense under the conditions of preparation. The formation of a fused triazolidine ring occurs regularly if aldehydes are treated with ammonia and chloramine to give diaziri-dines [Eq. (39)]. If, however, chloral is added previously to the reaction mixture, the 3-aIkyl-diaziridines (45) arc caught as their chloral adducts. By the alkali fission of these chloral adducts, 3-alkyl-diaziridines, e.g. (45), can be prepared. 

During the first month of this experiment, it was realized that this reaction is extremely variable. Thus, diverse amines (ammonia, primary and secondary amines, hydrazine derivatives, hydroxylamines) 13, carbonyl compounds (aldehydes, ketones) 14, acid components 15 or their anions (H2O, Na2S203, H2Se, R2NH, RHN-CN, HN3, HNCO, HNCS, RCO2H, RCOSH, ROCO2H, etc.), and the isocyanides could form the a-adducts 16 that rearrange into their products 17 (Scheme 1.5). 

Our own group is also involved in the development of domino multicomponent reactions for the synthesis of heterocycles of both pharmacologic and synthetic interest [156]. In particular, we recently reported a totally regioselective and metal-free Michael addition-initiated three-component substrate directed route to polysubstituted pyridines from 1,3-dicarbonyls. Thus, the direct condensation of 1,3-diketones, (3-ketoesters, or p-ketoamides with a,p-unsaturated aldehydes or ketones with a synthetic equivalent of ammonia, under heterogeneous catalysis by 4 A molecular sieves, provided the desired heterocycles after in situ oxidation (Scheme 56) [157]. A mechanistic study demonstrated that the first step of the sequence was a molecular sieves-promoted Michael addition between the 1,3-dicarbonyl and the cx,p-unsaturated carbonyl compound. The corresponding 1,5-dicarbonyl adduct then reacts with the ammonia source leading to a DHP derivative, which is spontaneously converted to the aromatized product. 

The addition of nucleophiles to the carbonyl group may be catalysed by acids obtained by the protonation of the carbonyl oxygen (equilibrium 26). Acid catalysis can also occur during the elimination step which follows the addition step. For example, the reactions of aldehydes with amines (and of all the ammonia derivatives) to form imines are generally assumed to occur in two steps the first is the addition of nucleophile to yield a gem amino alcohol, the second includes the elimination of water from the tetrahedral adduct 138 (see Scheme 45). This elimination is usually thought to be catalysed by electrophiles171,212. 

Hantzsch dihydropyridine synthesis. The original Hantzsch synthesis2 involves condensation of two equivalents of a keto ester with an aldehyde in the presence of ammonia. In an enantioselective version.5 the chirality is introduced by use of a chiral hydrazone (2) of an alkyl acetoacetate prepared from 1. The anion of 2 is then treated with Michael acceptors to form adducts (3), which cyclize to 4-aryl-l,4-dihydropyridines (4), in 64-72% overall yield and in 84-98% ee. 

Figure 1 Strecker and related systems complex network of equilibrium reactions from aqueous solutions of cyanide, ammonia, and aldehyde, 1. Pathways for exiting the equilibrated network correspond to (a) cyanohydrin hydrolysis, (b) aminonitrile hydrolysis, and (c) Biicherer-Bergs reaction. Adducts 6 and 7 and other hydrolysis products can be formed at high concentrations of reactants.

Imidazole-4-carboxylates have been made from amidines derived from or-ainino acids (see Section 2.2.1 and Table 2.2.1), by Claisen rearrangement of the adduct formed when an arylamidoxime reacts with a propiolate ester (see Section 2.2.1 and Scheme 2.2.6), from a-aminocarbonyls with cyanates or thiocyanates (see Section 4.1 and Table 4.1.1), from a-oximino- 6-dicarbonyl compounds heated with an aUcylamine (see Section 4.1 and Scheme 4.1.7), and by anionic cycloaddition of an alkyl isocyanoacetate to diethoxyacetonitrile (see Section 4.2 and Scheme 4.2.11 see also Scheme 4.2.12). A further useful approach is to use an appropriate tricarbonyl compound with an aldehyde and a source of ammonia (see Chapter and Scheme 5.1.1). Irradiation of 1-alkenyltetrazoles bearing an ester substituent may have applications (see Section 6.1.2.3). 

The polymeric material from the plain caramel is generated from the condensation reactions of the aldehydes and ketones formed by heating the sugar with bases or acids. The ammonia caramel is formed in a Maillard type reaction [2] where carbonyl compounds react with amino groups or ammonia. This type of compound will be further presented in Sections 11.2 and 11.3. Sulfite caramel is also a Maillard type polymer. However, as hydrogen sulfites form stable adducts with aldehydes and ketones, the sulfite caramels include in their structure sulfite groups. 

Condensations. Alumina promotes the formation of a-hydroxyphosphonate esters from aromatic aldehydes and dialkyl phosphonates, and the adducts are converted to a-aminophosphonate esters on reaction with ammonia. A solvent-free synthesis of a-nitro ketones comprises mixing nitroalkanes, aldehydes, and neutral alumina and oxidizing the adducts with wet, alumina-supported CrOj (15 examples, 68-86%). The Knoevenagel reaction, the Michael addition of nitromethane to gcm-diactivated alkenes, and the formation of iminothiazolines from thioureas and a-halo ketones are readily effected with alumina under microwave irradiation. 

C 77.38%, H 7.58%, N 15.04%. Found in coal tar and in bone oil. Synthesis (40-50% yield) from cyclohexyl-amine with excess ammonia and zinc chloride at 350 Nordt, PB Report 704 (1941). Prepn from ethylene -mercuric acetate adduct and ammonia water (70% yield) Gumboldt, Feichtinger. Z. Naturforsch. 4b, 123 (1949). Review of the various methods of condensing aldehydes, ketones, ethylene, butadiene, etc., with ammonia F. Brody, P. R. Ruby in A. Weissberger, 77te chemistry of Heterocyclic Compounds, vol. 14, part I (New York, i960) pp 99-589. Contains 1851 references. 

A large number of oc-amino sulfonic acids have been prepared from the hydrogen sulfite adducts ( -hydroxy sulfonic acids) and ammonia or amines at or slightly above room temperature. 976They are very important intermediates in the Knoevenagel-Bucherer form of the Strecker amino acid synthesis (cf. page 877). In this synthesis the aldehyde-bisulfite compounds are converted by ammonia or amines into a-amino sulfonic acids and thence by alkali cyanide or hydrogen cyanide into oc-amino nitriles, which are then hydrolysed ... 

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