Ketones, reaction with ammonia

The ketocarbene 4 that is generated by loss of Na from the a-diazo ketone, and that has an electron-sextet, rearranges to the more stable ketene 2 by a nucleophilic 1,2-shift of substituent R. The ketene thus formed corresponds to the isocyanate product of the related Curtius reaction. The ketene can further react with nucleophilic agents, that add to the C=0-double bond. For example by reaction with water a carboxylic acid 3 is formed, while from reaction with an alcohol R -OH an ester 5 is obtained directly. The reaction with ammonia or an amine R -NHa leads to formation of a carboxylic amide 6 or 7 ... 

One of the initial findings about bicyclic aziridines is reported in [88] the authors carried out the synthesis of 3,5a-dihydro-l//-azireno[l,2-c]imidazoles by reacting trwith carbonyl compounds in methanol saturated with ammonia in the presence of ammonium bromide. In particular, 2,2-dimethyl-6-(4-nitrophenyl)-4-phenyl-l,3-diazabicyclo[3.1.0]hex-3-ene 72 was obtained in the reaction of ketone 70 with ammonia and acetone 71 (Scheme 1.19). 

Trichloroacetamido)phenyl ketone.s 18 or their tribromo analogs are, in most cases, readily converted to the corresponding 4-substituted quinazolin-2(l//)-ones 19 by reaction with ammonia via loss of the trihalomethyl function. Under similar conditions, the 2-trifluoroac-etamide derivative reacts to yield 2-(trifluoromethyl)quinazoline. The mechani.sm of this... 

C=N- Reaction with ammonia, primary amines, hydrazine, hydroxyl-amine, semicarbazide, Girard D reagent Ketones [206], aldehydes [206] irreducible under given conditions better developed waves with some reducible compounds simultaneous determination of pyridoxal and pyridoxal-5-phosphate [193], 17-ketosteroids [238],... 

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. 

The facile synthesis of 2,3-difluoro-2-iodo-4-oxoalkanoate esters has provided starting materials for synthesis of 4-fluoropyrrole-2-carboxylate esters. The starting materials are prepared by photo-induced radical addition of difluoroiodomethyl ketones to acrylate esters. On reaction with ammonia, pyrroles were formed. <94TL4319> Some of the esters were converted to primary amides by aminolysis under the reaction conditions. 

Alexei Eugenivich Chichibabin (Kusemino, nr. Poltava, Russia, 17 March 1871 (O.S.)-Paris, 15 August 1945), assistant in the University of Moscow (1900) and professor (1909) in the Technical High-School there, published much work in organic chemistry, notably on tervalent carbon. The Chichibabin amination reaction (1914) involves the formation of 2-aminopyridine by heating pyridine with sodamide in toluene, and hydrolysis of the product with water. The Chichibabin pyridine synthesis involves the condensation of aldehydes, ketones, etc., with ammonia or amines to form substituted pyridines. ... 

Amino acids are prepared from aldehydes and ketones via reaction with ammonia and HCN or via reactions of halo-acids with ammonia or amines. Phthalimide is a useful amine-nucleophile surrogate for the preparation of amino acids. 

Like the a-bromo aldehydes and ketones, the a-bromo acids are very reactive in displacement reactions and therefore serve as sources of many a-substituted carboxylic acids (Fig. 19.46). A particularly important example is the formation of a-amino acids through reaction with ammonia. 

For example, if the reaction with ammonia is carried out in the presence of a reducing agent such as H2 and a metal catalyst, then the double bond will be reduced as it is formed, forming a primary amine. The reaction of an aldehyde or a ketone with excess anunonia in the presence of a reducing agent is called reductive amination. 

Aldehydes and ketones react with ammonia and primary amines to form imines. Reaction with aldehydes yields aldimines, and ketimines arise in reactions with ketones (Figure 8.28). Imines derived from aliphatic carbonyl compounds are generally unstable and are transformed to more stable products, such as amines, diamines and others. Secondary amines react with aldehydes and ketones with the formation of enamines (Figure 8.29). Imines are similarly flavour-active compounds derived from furan-2-carbaldehyde. For example, the aromas of Ar-furfuryl(isobutylidene)amine, N-(furfuryl)isopentyhdeneamine (8-155) and N-(furfurylidene)isobutylamine (8-156) reportedly resemble chocolate. 

A class of nitrogen containing compounds that was omitted from the section just dis cussed includes mines and their derivatives Immes are formed by the reaction of aide hydes and ketones with ammonia Immes can be reduced to primary amines by catalytic hydrogenation... 

Historically these compounds have been made in two-step processes. Eor smaller volumes, reaction of an appropriate ketone or aldehyde with a cyanide salt followed by treatment with an ammonium salt proves satisfactory (Strecker synthesis). Eor larger volumes, treatment of the ketone or aldehyde with HCN to produce a cyanohydrin, followed by treatment with ammonia has been practiced. However, in 1990, DuPont began practicing a new one-step... 

Ketone formation can also be avoided if one of the functional acyl halogens ia phosgene is blocked. Carbamyl chlorides, readily obtained by the reaction of phosgene with ammonia or amines, are suitable reagents for the preparation of amides ia direct Friedel-Crafts acylation of aromatics. The resulting amides can be hydroly2ed to the corresponding acids (134) ... 

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. 

Dicyclohexylarnine may be selectively generated by reductive alkylation of cyclohexylamine by cyclohexanone (15). Stated batch reaction conditions are specifically 0.05—2.0% Pd or Pt catalyst, which is reusable, pressures of 400—700 kPa (55—100 psi), and temperatures of 75—100°C to give complete reduction in 4 h. Continuous vapor-phase amination selective to dicyclohexylarnine is claimed for cyclohexanone (16) or mixed cyclohexanone plus cyclohexanol (17) feeds. Conditions are 5—15 s contact time of <1 1 ammonia ketone, - 3 1 hydrogen ketone at 260°C over nickel on kieselguhr. With mixed feed the preferred conditions over a mixed copper chromite plus nickel catalyst are 18-s contact time at 250 °C with ammonia alkyl = 0.6 1 and hydrogen alkyl = 1 1. 

---