Direct amination

So without direct amination we are confined to semi-direct ami-nation (Strike s terminology). In Strike s opinion, the direct addition of an azide (N3) counts. Once on the beta carbon, that azide is as good as an amine. But can we get an azide directly onto safrole without having to go thru the bromosafrole intermediate as was discussed earlier Maybe we can ... 

The next method Strike has for semi-direct amination is really weird, Strike is really exposing Strike s ignorance of chemistry with this dog. But if one looks hard at the articles cited, the potential is there. The authors came up with this little procedure that produced vicinal diamines out of alkenes [83]. Later they found that if they did a couple of things different, they would end up with a monoamine with the majority product being at the beta carbon. The following is a conjoining of the two paper s experimentals ... 

B) palladium(0)-catalyzed direct amination of the O-acetylated allylic alcohol. 

Aromatic amines can be produced by reduction of the corresponding nitro compound, the ammonolysis of an aromatic haUde or phenol, and by direct amination of the aromatic ring. At present, the catalytic reduction of nitrobenzene is the predominant process for manufacture of aniline. To a smaller extent aniline is also produced by ammonolysis of phenol. 

Treatment of a-hydroxy-ketones or -aldehydes with ammonium acetate (65BSF3476, 68BSF4970) results in the formation of dihydropyrazines, presumably by direct amination of the hydroxyketone followed by self-condensation (79AJC1281). Low yields of pyrazines have been noted in the electrolysis of ketones in admixture with KI and ammonia, and again it appears probable that the a-aminoketone derived by way of the a-iodoketone is the intermediate (69CI(L)237>. 

Where direct amination of chloro compounds has proved unsatisfactory, 4-alkoxy or 4-phenoxy intermediates have sometimes been used for reactions with amines or hydrazine. 

The ATPEs have a poly(propylene oxide) backbone widi amine endgroups, as shown in Scheme 4.4. There are several routes to such materials,25 but the only one in current commercial production is die direct amination of polyether polyols. A line of uretiiane-grade ATPEs is made by Huntsman under the tradename Jeffamine. Mono-, di-, and trifunctional products are available in molecular weights up to 5000 g/m. 

Activated aromatic compounds can be directly aminated with hydroxylamine in the presence of strong bases.Conditions are mild and yields are high. 

Much research has been carried out into direct amination of aromatic substrates, typified by the direct conversion of benzene to aniline using ammonia and a catalyst. Although there have been many patented routes conversions, are normally low, making them uneconomic. Modem catalysts based on rhodium and iridium, together with nickel oxide (which becomes reduced), have proved more active,and such is the research activity in this area that it is only a matter of time before such processes become widely used. 

Nearly quantitative yields of acetonitrile can be obtained by passing mixtures of NH3 and acetylene over zircon at 400-500°C [225], over CviOy on Y-alumina at 360°C [226] or by passing mixtures of NH, acetylene and hydrogen at 400-420°C over a mixture of zinc and thorium oxides on silica [227] or at 300-450°C over zinc oxide or zinc sulfate or zinc chloride on silica [228, 229], In such reactions, the role of traces of water has often been questioned. However, acetonitrile could be obtained under rigorously anhydrous conditions, thus demonstrating the direct amination of acetylene with NH,. It was also reported that ethyUdeneimine can be obtained in up to 26% yield [225], However, in the Ught of more recent work [230, 231] the product was most probably 2,4,6-trimethyl-l,3,5-hexahydrotriazine. 

Desrosiers, P., Guan, S.H., Hagemeyer, A. et al. (2003) Application of combinatorial catalysis for the direct amination of benzene to aniline. Catal. Today, 81, 319. 

In the presence of zinc chloride, stereoselective aldol reactions can be carried out. The aldol reaction with the lithium enolate of /-butyl malonate and various a-alkoxy aldehydes gave anti-l,2-diols in high yields, and 2-trityloxypropanal yielded the syn-l,2-diol under the same conditions.633 Stoichiometric amounts of zinc chloride contribute to the formation of aminoni-tropyridines by direct amination of nitropyridines with methoxyamine under basic conditions.634 Zinc chloride can also be used as a radical initiator.635... 

Furthermore, the first direct amination of benzene has been achieved and has generated the aniline derivative in an acceptable yield (Equation (103)). Recently, a cationic copper(i) complex 132-catalyzed nitrene transformation to the C-H bonds of the electron-rich arene was reported by Sadighi and co-workers (Equation (104)).285... 

The application of the Chichibabin amination to effect a direct amination of quinazoline has been reported. It gives 4-aminoquinazoline (60MII) as well as 2,4-diaminoquinazoline (59GEP958197). No mechanistic details were discussed, but it can be expected (based on the experience with the amination with 4-phenyl- and 5-phenylpyrimidine) that amination of quinazoline would also involve, at least partly, participation of the Sn(ANRORC) mechanism. Amination with N-labeled potassium amide/liquid ammonia will certainly shed some light on the mechanism operative in this Chichibabin amination. 

The amino group of 10H-benzo[i7]thieno[2,3-e][l,4]diazepin-4-amine 253 can be substituted with N-methyl piperazine by direct amination under thermal conditions (Scheme 53, Section 3.1.3 (1997BMCL25)). 

Formation of thiolactam 276 and its direct amination with N-methyl piperazine (1994JHC1053) is one of the routes to piprerazines 277 (Scheme 59, Section 3.2.3 (1992AF896, 2002JHC163)). Alternatively, 7-fluorobenzo[l7]thieno[2,3-/][l,4]oxaze-pin-10(9H)-one 279 undergoes chlorination and sequential amination to 277. 

Sulfonylhydroxylamines and hydroxylamine O-sulfonic acid have found wide apph-cation in synthesis of amines from achiral or chiral organoboranes and boronate esters and the hydroboration-amination methodology is successfully used for direct amination of alkenes. 0-Sulfonyloximes were also found to be good reagents for synthesis of amines from organomagnesium, -copper and -zinc reagents. 

Direct amination of benzo[l,2-aqueous base with hydroxylamine-0-sulfonic acid gives a mixture of three diamino derivatives and two monoamino derivatives (Equation (15)). The combined yields of diamino and monoamino products are 45% and 48%, respectively. The three diamino derivatives can be separated by fractional crystallization from ethanol <86JOC979>. A-Amination of triazoles can also be achieved by treatment with NaH in DMF followed by O-amino-2,4-dinitrophenol <85TL335> or 0-(mesitylsulfonyl)hydroxyamine (9lJCS(Pl)2045>. 

Aminobenzotriazoles can be synthesized by two methods (i) direct amination of benzotriazole. This method is simple, however, all possible isomers are formed <86JOC979> (ii) Cyclization of 2-hydrazinobenzenediazonium salts. Reductive cyclization of 2-azobenzenediazoniums (851) gives compounds (852) (Equation (88)). The diazotization of protected 2-hydrazino-anilines (853) followed by hydrolysis allows the preparation of 1-aminobenzotriazoles (854) (Equation (89)). 

In gas phase reactions the size of catalyst libraries can be over couple of thousands. For instance, in the synthesis of aniline by direct amination of benzene around 25000 samples were screened in about a year [15], however, the optimization method used was not discussed. In contrast, in liquid phase reactions taking place at elevated pressure and temperature, due to technical difficulties the rational approach does not allow testing libraries containing more than 200 250 catalysts. Consequently, the informatic platform and the strategy used to design catalyst libraries for high-pressure liquid phase reactions should have very unique optimization tools. 

In this transamination, the effect of para substitient groups has been studied using fluorinated phenylpyruvic acids and L-aspartic acid. From these results, the migratory preference is H > F > Cl > Br > CF3. This order has been attributed to the bulkiness of the substituted group [57]. Direct amination of p-substituted succinic acid with phenylalanine ammonialyase (EC 4.3.1.5) has suggested very high substrate specificity that the order of reaction rate is m-F o-F P-p-F >CF3. 

Direct Amination at an Activated Position Alkyamino-de-hydrogenation, etc. 

Direct amination of aromatic rings 1-25 Aminoalkylation of aromatic rings 1-32 Rearrangement of N-nitroamines 1-33 Rearrangement of N-nitrosoamines... 

Considering the ample possibilities to generate new carbon-hereoatom bonds, particularly the wide range of oxygenation reactions, only limited attempts have been made to carry out direct amination of hydrocarbons. A few examples of animation of alkanes, alkenes, and aromatics are discussed briefly here. 

Direct amination of quinoxalinones with hydroxylamine-O-sulfonic acid produces the 1-amino derivatives (135) in 70-80% yield, and subsequent oxidation with lead tetraacetate gives the 1,2,4-benzotriazines (138). Benzotriazine formation probably involves the formation of an intermediate nitrene (136), ring expansion to a benzo-triazepinone (137) and subsequent loss of carbon monoxide. The nitrene (136 R = Ph) was trapped as the sulfoximide 139 when the oxidation was carried out in the presence of dimethyl sulfoxide.147... 

P,y-Diamino analogues 49 of statine are prepared stereoselectively starting from the O-methyl hydroxamate derivative of N-protected statine. The reaction sequence involves the formation of a p-lactam intermediate obtained by internal cyclization under Mitsunobu conditions.184 Alternatively, direct amination of either a p-oxo ester 31 followed by reduction of the resulting enamine 50, 85 or by reduction of the corresponding ,p-unsaturated ester, 88 gives an enantiomeric mixture of the corresponding unprotected p-amine, which is protected by a carbamate prior to chromatographic separation (Scheme 20). 

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