Amines variations

Lundstedt, T., Carlson, R. and Shabana, R.. Optimum Conditions for the Willgerodt-Kindlei Reaction. 3. Amine Variation. Ada Chem. Scand., 1987, B41, 157-163. 

This is not an example of solvent selection. It is given to show a selection of co-substrates from subgroups in the determination of the scope of a reaction, viz, amine variation in the Willgerodt-Kindler reaction. The general features of this reaction were discussed in Chapter 6. 

It has for long been assumed that morpholine is the preferred amine in this reaction, and that other amines generally give inferior results. With the aim of examining the scope of the reaction with regard to amine variation, the reaction was run with a series of amines selected by their principal properties. Acetophenone was used as the ketone substrate in these reactions, and quinoline was used as a solvent. The reason for using quinoline was that it permits a large span of the reaction temperature (b.p 237 ° C). 

The first example of a "uniform spread" design in the study of solvent varation was applied to the Willgerodt-Kindler reaction.[3] It is not reproduced here, since it is very similar to the above example of amine variation. A very clear application of the principle of "uniform spread" is given in an example on the Fischer indole synthesis in the next chapter. 

The Morita-Baylis-Hillman reaction is, in general, a carbon-carbon bondforming reaction of an a,(3-unsaturated compound with an aldehyde mediated by an organic nucleophilic base resulting in the formation of an allylic alcohol. Morita reported the use of a phosphine as catalyst and Baylis and Hillman used a tertiary amine. Variation of the electrophile to electron-deficient alkenes in a Michael-Michael elimination sequence leads to homo- and heterodimerisation and is known as the Rauhut-Currier reaction. The electrophilic aldehyde could be substituted by an imine or derivative in the aza-Morita-Baylis-Hillman reaction. Recently, there has been an increase in the use of this reaction for the construction of many different targets using many different amine derived catalysts. Scheme 2.2 shows a general view of this reaction and the accepted mechanism. ... 

Buchwald quickly parlayed this transformation into a versatile indole synthesis via oxidation of intermediate indolines prepared using the above intramolecular Buchwald-Hartwig amination. Variations leading directly to indoles and related nitrogen-containing heterocycles quickly followed and are described below. 

CO. Alkynes will react with carbon monoxide in the presence of a metal carbonyl (e.g. Ni(CO)4) and water to give prop>enoic acids (R-CH = CH-C02H), with alcohols (R OH) to give propenoic esters, RCH CHC02R and with amines (R NH2) to give propenoic amides RCHrCHCONHR. Using alternative catalysts, e.g. Fe(CO)5, alkynes and carbon monoxide will produce cyclopentadienones or hydroquinols. A commercially important variation of this reaction is hydroformyiation (the 0x0 reaction ). 

A further improvement is embodied in the Klndler variation of the Willgerodt reaction this consists in heating the ketone with approximately equal amounts of sulphur and a dry amine instead of aqueous ammonium polysulphide. The principal product is a thioamide, and hydrolysis with acid or alkali affords the carboxylic acid, usually in good yield. 

A variation of the classical reductive amination procedure uses sodium cyanoboro hydride (NaBH3CN) instead of hydrogen as the reducing agent and is better suited to amine syntheses m which only a few grams of material are needed All that is required IS to add sodium cyanoborohydride to an alcohol solution of the carbonyl compound and an amine... 

In a variation of the Raschig process for making hydrazine, amines rather than ammonia ate reacted with chloramine to give the corresponding alkyl hydrazine ... 

A variation of this method involves the conversion of the amine into the amine hydrochloride prior to treatment with phosgene. This method has the advantage of producing generally cleaner products by retarding the secondary reaction of the free amine with carbamoyl chloride. 

Phosgene addition is continued until all the phenoHc groups are converted to carbonate functionahties. Some hydrolysis of phosgene to sodium carbonate occurs incidentally. When the reaction is complete, the methylene chloride solution of polymer is washed first with acid to remove residual base and amine, then with water. To complete the process, the aqueous sodium chloride stream can be reclaimed in a chlor-alkah plant, ultimately regenerating phosgene. Many variations of this polycarbonate process have been patented, including use of many different types of catalysts, continuous or semicontinuous processes, methods which rely on formation of bischloroformate oligomers followed by polycondensation, etc. 

A variation of this procedure is used for sulfisomidine because of the different character of the amino group in the 4-position of a pyrimidine ring. Two moles of the sulfonyl chloride are condensed with one mole of 4-amino-2,6-dimethy1pyrimidine in the presence of triethylamine. The resulting bis(acetylsulfanilyl) derivative is readily hydrolyzed to the product. The formation of the bis(acetylsulfanilyl) derivative has also been employed for other heterocycHc amines, eg, for synthesis of sulfathiazole and sulfamoxole (44), but the 1 1 reaction is probably preferable. 

The route to 3-bromothiophene utilises a variation of the halogen dance technology (17). Preferably, 2,5-dibromothiophene [3141-27-3] is added to a solution of sodamide in thiophene containing the catalyst tris(2-(2-methoxyethoxy)ethyl)amine (l DA-1) (33) at temperatures marginally below reflux. On completion, quenching exothermically Hberates ammonia gas the organic phase is separated, washed, and distilled, and foremnning thiophene is recycled. Material of 97—98% purity is isolated. 

Some commercial durable antistatic finishes have been Hsted in Table 3 (98). Early patents suggest that amino resins (qv) can impart both antisHp and antistatic properties to nylon, acryUc, and polyester fabrics. CycHc polyurethanes, water-soluble amine salts cross-linked with styrene, and water-soluble amine salts of sulfonated polystyrene have been claimed to confer durable antistatic protection. Later patents included dibydroxyethyl sulfone [2580-77-0] hydroxyalkylated cellulose or starch, poly(vinyl alcohol) [9002-86-2] cross-linked with dimethylolethylene urea, chlorotria2ine derivatives, and epoxy-based products. Other patents claim the use of various acryUc polymers and copolymers. Essentially, durable antistats are polyelectrolytes, and the majority of usehil products involve variations of cross-linked polyamines containing polyethoxy segments (92,99—101). 

The Bart reaction is successful with a wide variety of aromatic and heterocycHc amines. A variation in which an aromatic amine, in the presence of arsenic trichloride, is dia2oti2ed in an organic solvent (the ScheUer reaction) has also found wide appHcation. Both arsonic and arsinic acids can be prepared by the ScheUer reaction which often gives better yields than the Bart reaction with electron-attracting substituents on the aromatic ring. For the commercial preparation of 4-aminophenylarsonic acid [98-50-0] (arsaniUc acid), C HgAsNO, and 4-hydroxyphenylarsonic acid [98-14-6] C H AsO, the Bnchamp reaction is used ... 

Diacylhydrazines (32) on heating with a primary amine undergo cyclization to the 1,2,4-triazole derivative (38). It is assumed that the amidrazone (37) is an intermediate in the reaction. Most practical syntheses of 1,2,4-triazoles now utilize an amidrazone or a derivative of this alicyclic intermediate containing three nitrogen atoms, and these variations are discussed in Chapter 4.12. 

It is thus seen that as a class the primarily aliphatic amines provide fast-curing hardeners for use at room temperatures. With certain exceptions they are skin sensitisers. The chemical resistance of the hardened resins varies according to the hardener used but in the case of the unmodified amines is quite good. The hardened resins have quite low heat distortion temperatures and except with diethylenetriamine seldom exceed 100°C. The number of variations in the properties obtainable may be increased by using blends of hardeners. 

Other nylons are made by varying the molecular length of the diamines and the dibasic acids Nylon-fi. in u.ses sebacic acid (10 carbon atoms), nylon-11 uses an acid from castor oil, and nylon-12 uses butadiene. These variations decrease moisture absorption. Other variations use amines with a ring structure, e.g., the aromatic nylons to give polymers with softening points above 577 F,... 

After determination of the seasonal variation in alkaloidal content of the leaves, stems and roots of belladonna and the production of evidence that there is a considerable movement of alkaloid upwards from root to leaves and a small transport in the opposite direction, Cromwell found that of a laige number of amines injected, with or without glucose, into... 

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