Ammonia carbonyl

Officially, the history of MCRs dates back to the year 1850, with the introduction of the Strecker reaction (S-3CR) describing the formation of a-aminocyanides from ammonia, carbonyl compounds, and hydrogen cyanide [4]. In 1882, the reaction progressed to the Hantzsch synthesis (H-4CR) of 1,4-dihydropyridines by the reaction of amines, aldehydes, and 1,3-dicarbonyl compounds [5], Some 25 years later, in 1917, Robinson achieved the total synthesis of the alkaloid tropinone by using a three-component strategy based on Mannich-type reactions (M-3CR) [6]. In fact, this was the earliest application of MCRs in natural product synthesis [7]. 

Ugi and Domling have shown that the U-4CR can also be combined with other MCRs, thus creating sequences which involve up to nine different substrates [33]. An example of such an approach is the combination of an Ugi-4CR with the as-yet not mentioned Asinger reaction (A-3CR or A-4CR). The latter allows the formation of thiazolines from ammonia, carbonyl compounds and sulfides [34]. As shown in Scheme 9.7, a mixture of a-bromoisobutyraldehyde, isobutyraldehyde, sodium hy-drogensulfide and ammonia yields the imine 9-38 which, by reaction with t-butyl-isocyanide, methanol, and C02, led to the final product 9-39 [35]. 

One of the very first methods for the preparation of a-aminophosphonic acids appears to be the one described by Kabachnik and Medved [8]. The Kabachnik-Fields reaction is still very useful, especially for the preparation of dialkyl 1-aminoalkanephosphonates. According to this method, a-aminophosphonates were obtained reacting ammonia, carbonyl compounds (aldehydes and ketones), and dialkyl H-phosphonate. A little later. Fields [9] presented a method of synthesis of 1-aminoalkylphosphonic acids by replacing ammonia with amine—reacting both (aldehydes and ketones) with ammonia, or amine and dialkyl H-phosphonate to give dialkyl esters of 1-aminoalkylphosphonic acid (see Appendix). Hydrolysis of the esters produced free aminoalkylphosphonic acids. Yields of aminophosphonates vary from 40 to 47%. 

Since Kabachnik and Medved found that a-hydroxyalkylphosphonates are present in the reaction mixture of ammonia, carbonyl compound, and dialkyl H-phosphonate, they accepted that the reaction proceeds via formation of a-hydioxyalkylphosphonate followed... 

Cobalt has an odd number of electrons, and does not form a simple carbonyl in oxidation state 0. However, carbonyls of formulae Co2(CO)g, Co4(CO)i2 and CoJCO),6 are known reduction of these by an alkali metal dissolved in liquid ammonia (p. 126) gives the ion [Co(CO)4] ". Both Co2(CO)g and [Co(CO)4]" are important as catalysts for organic syntheses. In the so-called oxo reaction, where an alkene reacts with carbon monoxide and hydrogen, under pressure, to give an aldehyde, dicobalt octacarbonyl is used as catalyst ... 

This olionge involves the oxidation of the alcohol grouping of C or C to carbonyl by the action of a second molecule of phenylhydrazine the latter is reduced to aniline and ammonia. Alternative explanations of this reaction have been advanced, but these cannot be discussed here (see, however. Section 111,139,6). 

The reaction between sodium acetylide in liquid ammonia solution and carbonyl compounds gives a-acetylenyl carbinols (compare Section 111,148), for example ... 

The reaction is carried out at low temperature in aqueous medium and then allowed to stand overnight (221). Ammonium thiocarbamate is prepared from a cold saturated solution of ammonium thiocyanate, which is gradually added to dilute sulfuric acid at 25°C. The liberated carbonyl sulfide is passed into a saturated solution of alcoholic ammonia at about 10°C (221). The fairly low yield indicates that the reaction has not been greatly developed. 

Ammonia and amines undergo conjugate addition to a 3 unsaturated carbonyl compounds (Section 18 12) On the basis of this information predict the pnncipal organic product of each of the following reactions... 

Ammonia reacts with the ketone carbonyl group to give an mine (C=NH) which is then reduced to the amine function of the a ammo acid Both mine formation and reduc tion are enzyme catalyzed The reduced form of nicotinamide adenine diphosphonu cleotide (NADPH) is a coenzyme and acts as a reducing agent The step m which the mine is reduced is the one m which the chirality center is introduced and gives only L glutamic acid... 

Neutral and Cationic Ligands. Neutral and cationic ligands are used without change in name and are set off with enclosing marks. Water and ammonia, as neutral ligands, are called aqua and ammine, respectively. The groups NO and CO, when linked directly to a metal atom, are called nitrosyl and carbonyl, respectively. 

Acetaldehyde can be isolated and identified by the characteristic melting points of the crystalline compounds formed with hydrazines, semicarbazides, etc these derivatives of aldehydes can be separated by paper and column chromatography (104,113). Acetaldehyde has been separated quantitatively from other carbonyl compounds on an ion-exchange resin in the bisulfite form the aldehyde is then eluted from the column with a solution of sodium chloride (114). In larger quantities, acetaldehyde may be isolated by passing the vapor into ether, then saturating with dry ammonia acetaldehyde—ammonia crystallizes from the solution. Reactions with bisulfite, hydrazines, oximes, semicarb azides, and 5,5-dimethyl-1,3-cyclohexanedione [126-81 -8] (dimedone) have also been used to isolate acetaldehyde from various solutions. 

Compounds with active hydrogen add to the carbonyl group of acetone, often followed by the condensation of another molecule of the addend or loss of water. Hydrogen sulfide forms hexamethyl-l,3,5-trithiane probably through the transitory intermediate thioacetone which readily trimerizes. Hydrogen cyanide forms acetone cyanohydrin [75-86-5] (CH2)2C(OH)CN, which is further processed to methacrylates. Ammonia and hydrogen cyanide give (CH2)2C(NH2)CN [19355-69-2] ix.orn. 6<55i the widely used polymerization initiator, azobisisobutyronitrile [78-67-1] is made (4). 

Analogously, aldehydes react with ammonia [7664-41-7] or primary amines to form Schiff bases. Subsequent reduction produces a new amine. The addition of hydrogen cyanide [74-90-8] sodium bisulfite [7631-90-5] amines, alcohols, or thiols to the carbonyl group usually requires the presence of a catalyst to assist in reaching the desired equilibrium product. 

The carbonylation of methanol [67-56-1] to methyl formate ia the presence of basic catalysts has been practiced iadustriaHy for many years. Ia older processes for formic acid utili2ing this reactioa, the methyl formate [107-31-3] reacts with ammonia to give formamide [75-12-7] which is hydroly2ed to formic acid ia the preseace of sulfuric acid ... 

The direct, one-step production of DMF from carbon monoxide, hydrogen, and ammonia has also been reported. A mthenium carbonyl catalyst is used, either ia a polar organic solvent (20) or ia a phosphonium molten salt medium (21). 

Ethynylation. Base-catalyzed addition of acetylene to carbonyl compounds to form -yn-ols and -yn-glycols (see Acetylene-DERIVED chemicals) is a general and versatile reaction for the production of many commercially useful products. Finely divided KOH can be used in organic solvents or Hquid ammonia. The latter system is widely used for the production of pharmaceuticals and perfumes. The primary commercial appHcation of ethynylation is in the production of 2-butyne-l,4-diol from acetylene and formaldehyde using supported copper acetyHde as catalyst in an aqueous Hquid-fiHed system. 

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. 

Ma.nufa.cture. Nickel carbonyl can be prepared by the direct combination of carbon monoxide and metallic nickel (77). The presence of sulfur, the surface area, and the surface activity of the nickel affect the formation of nickel carbonyl (78). The thermodynamics of formation and reaction are documented (79). Two commercial processes are used for large-scale production (80). An atmospheric method, whereby carbon monoxide is passed over nickel sulfide and freshly reduced nickel metal, is used in the United Kingdom to produce pure nickel carbonyl (81). The second method, used in Canada, involves high pressure CO in the formation of iron and nickel carbonyls the two are separated by distillation (81). Very high pressure CO is required for the formation of cobalt carbonyl and a method has been described where the mixed carbonyls are scmbbed with ammonia or an amine and the cobalt is extracted as the ammine carbonyl (82). A discontinued commercial process in the United States involved the reaction of carbon monoxide with nickel sulfate solution. 

Carbonyl sulfide reacts with chlorine forming phosgene (qv) and sulfur dichloride [10545-99-0] and with ammonia forming urea and ammonium sulfide [12135-76-1]. Carbonyl sulfide attacks metals, eg, copper, ia the presence of moisture and is thought to be iavolved ia atmospheric sulfur corrosion (27,28). Its presence ia propane gas at levels above a few ppm may cause the gas to fail the copper-corrosion test. 

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