Ammonia aldehydes with

Most processes in use in the 1990s make pyridines by condensation of ammonia with aldehydes or ketones either in the vapor phase or in the Hquid phase. These processes are based on the pioneering work of Chichibabin (3). Commercial practice of that process was not reali2ed until some 50 years after its discovery (74,75). 

Despite the increasing information on the photochemistry of 2,4-dienones and other unsaturated ketones, as well as on the ring-chain valence isomerism of halogen-substituted pyran and dihydi opyran systems,the data are still very scarce. The intermediate formation of pyrans valence-isomeric with unsaturated carbonyl compounds in the pyridine syntheses based on reactions of ammonia with aldehydes or ketones, advocated by various authors (cf. Section II,B,2,f), is still rather speculative. (See also Section II,B,2,e for the valence isomerism of 5-chloro-2,4-dienones with pyrylium chlorides.)... 

Good yields of secondary amines are achieved using both the methods in the reactions of aromatic and aliphatic aldehydes as well as of diaUcyl ketones and cycloalkanones with aliphatic and alicyclic amines (and ammonia). Anilines give low yields, but when 2 equiv is used in the sodium hydrogen telluride method, the yields are improved. In the reaction of ammonia with aldehydes, symmetrical secondary amines are obtained, whereas glu-taraldehyde and amines lead to N-substituted piperidines. 

Synthesis of 1,3,5-triazine derivatives from the reaction of ammonia with aldehydes 508... 

So far, all of the examples have involved primary amines. The reaction of ammonia with aldehydes and ketones also forms imines, but the products are unstable and cannot usually be isolated. If a secondary amine is used, an enamine, rather than an imine, is formed. An enamine has an amino group bonded to one of the carbons of a CC double bond. It is related to the imine in the same manner as an enol is related to a ketone (see Section 11.6). The mechanism for its formation can be outlined as follows ... 

Unlike aliphatic aldehydes (with the exception of formaldehyde which 3delds hexamethylenetetramine. Section 111,67) benzaldehyde yields hydrobenzamide (and not an aldehyde ammonia) with ammonia ... 

Reactions. The chemical properties of cyanoacetates ate quite similar to those of the malonates. The carbonyl activity of the ester function is increased by the cyano group s tendency to withdraw electrons. Therefore, amidation with ammonia [7664-41-7] to cyanoacetamide [107-91-5] (55) or with urea to cyanoacetylurea [448-98-2] (56) proceeds very easily. An interesting reaction of cyanoacetic acid is the Knoevenagel condensation with aldehydes followed by decarboxylation which leads to substituted acrylonitriles (57) such as (29), or with ketones followed by decarboxylation with a shift of the double bond to give P,y-unsaturated nitriles (58) such as (30) when cyclohexanone [108-94-1] is used. 

By-Products. Almost all commercial manufacture of pyridine compounds involves the concomitant manufacture of various side products. Liquid- and vapor-phase synthesis of pyridines from ammonia and aldehydes or ketones produces pyridine or an alkylated pyridine as a primary product, as well as isomeric aLkylpyridines and higher substituted aLkylpyridines, along with their isomers. Furthermore, self-condensation of aldehydes and ketones can produce substituted ben2enes. Condensation of ammonia with the aldehydes can produce certain alkyl or unsaturated nitrile side products. Lasdy, self-condensation of the aldehydes and ketones, perhaps with reduction, can lead to alkanes and alkenes. 

In the case of the bases derived from quaternary heterocyclic ammonium salts, the carbinolamines (5) can react as cyclic aldehyde-ammonias with many reagents with which the amino-aldehyde (7) could react. However, reactions of the carbinolamines which are not characteristic of amino-aldehydes are also known. Carbinolamines can easily be reconverted into the quaternary salts by the action of dilute acids, and they form alkyl ethers very easily with alcohols. If these last reactions do not occur, then this is convincing evidence for the base possessing the amino-aldehyde structure. However, if these reactions do occur this does not provide unambiguous confirmation of the carbinolamine structure. They are also given by the bi-molecular ethers (8), and, in the case of a tautomeric equilibrium... 

The mechanism proposed by Emmons thus corresponds in part to the decomposition of the trialkyl-oxaziranes by ferrous salts. By radical attack on the 7V-alkyl group of the oxazirane, the radical 32 is formed which rearranges with ring opening to 33. Radical 33 propagates the chain by attack on a further molecule of oxazirane. It takes up an H-atom and is decomposed to ketone and ammonia. The aldehyde produced from the M-alkyl group is converted to tar. 

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. 

Dihydropyridines from condensation of /3-ketoesters with aldehydes and ammonia... 

A primary or secondary amine can be used, as well as ammonia. With respect to the carbonyl component used, the best results have been obtained with aromatic aldehydes and with high boiling ketones. 

The Hantsch pyridine synthesis provides the final step in the preparation of all dihydrop-yridines. This reaction consists in essence in the condensation of an aromatic aldehyde with an excess of an acetoacetate ester and ammonia. Tlie need to produce unsymmetrically subsrituted dihydropyridines led to the development of modifications on the synthesis. (The chirality in unsymmetrical compounds leads to marked enhancement in potency.) Methyl acetoacetate foniis an aldol product (30) with aldehyde 29 conjugate addition of ethyl acetoacetate would complete assembly of the carbon skeleton. Ammonia would provide the heterocyclic atom. Thus, application of this modified reaction affords the mixed diester felodipine 31 [8]. 

The addition of ammonia to aldehydes or ketones does not generally give useful products. According to the pattern followed by analogous nucleophiles, the initial products would be expected to be hemiaminals, but these compounds are generally unstable. Most imines with a hydrogen on the nitrogen spontaneously poly-... 

In the vast majority of gas-solid reactions, gaseous or evaporated compounds react at the surface of a solid catalyst. These catalytic processes are very frequently used in the manufacture of bulk chemicals. They are much less popular in processing of the large molecules typical of fine chemistry. These molecules are usually thermally sensitive and as such they will at least partially decompose upon evaporation. Only thermally stable compounds can be dealt with in gas-solid catalytic processes. Examples in fine chemicals manufacture are gas-phase catalytic aminations of volatile aldehydes, alcohols, and ketones with ammonia, with hydrogen as... 

Besides direct reduction, a one-pot reductive amination of aldehydes and ketones with a-picoline-borane in methanol, in water, and in neat conditions gives the corresponding amine products (Scheme 8.2).40 The synthesis of primary amines can be performed via the reductive amination of the corresponding carbonyl compounds with aqueous ammonia with soluble Rh-catalyst (Eq. 8.17).41 Up to an 86% yield and a 97% selectivity for benzylamines were obtained for the reaction of various benzaldehydes. The use of a bimetallic catalyst based on Rh/Ir is preferable for aliphatic aldehydes. 

Glycine and the other amino acids are probably formed via the Strecker-cyano-hydrin synthesis (which has been known for more than 150 years) from aldehyde, HCN and ammonia, with subsequent hydrolysis (Strecker, 1850,1854 Miller, 1953). 

The Sn2 reaction of quinazolinone 147 with phenylhydrazine was followed by rearrangement of the tautomerized intermediate 148 <00T7987>. The loss of both ammonia and aniline was followed by the addition of a second equivalent of phenylhydrazine to the resulting imine to produce quinazolinone hydrazone 149. Subsequent Fischer indolization of 149 followed by condensations with aldehydes led to 7-azarutacarpines. 

Sodium cyanoborohydride NaBIpCN in methanol is the reagent of choice for the reductive alkylation of ammonia, primary aliphatic and aromatic amines and secondary aliphatic amines with aldehydes and relatively unhindered ketones (equation 53). 

The reaction involves formation of an imine through reaction of ammonia with the ketone, followed by reduction of this imine (see Section 7.7.1). As we noted earlier (see Section 15.1.1), nicotinamide coenzymes may also participate in imine reductions as well as aldehyde/ketone reductions, further emphasizing the imine-carbonyl analogy (see Section 7.7.1). The reverse reaction, removal of ammonia from glutamate, is also of importance in amino acid catabolism. 

The synthesis of oxaziridine-fused quinazolinones 277 follows a different route. Quinazolinones 274 (R = Et, nPr, n-hexyl) can readily be prepared by reacting 2-oxo-l-cyclohexanecarboxamide with aldehydes in the presence of ammonia solution. In the reaction of 274 and monoperoxyphthalic acid, the hydroxyoxaziridines 277 were formed via the presumed intermediates 275 and 276. No spectroscopic evidence was given for 277, nor was its relative configuration investigated [76JPR(318)895]. 

Mannich Reaction The reaction of a compound with a reactive hydrogen with aldehydes (non-enol forming) and ammonia or a primary or secondciry amine to form a Mannich base (ciminomethylated compound). 

The formation of the diacetamide derivatives requires, in this theory, the existence of two acetyl groups so located in the molecule, that they can react, through the ammonia, with the aldehyde carbon. 

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