Secondary amines, reaction with carbon

Hydroxylysine (328) was synthesized by chemoselective reaction of (Z)-4-acet-oxy-2-butenyl methyl carbonate (325) with two different nucleophiles first with At,(9-Boc-protected hydroxylamine (326) under neutral conditions and then with methyl (diphenylmethyleneamino)acetate (327) in the presence of BSA[202]. The primary allylic amine 331 is prepared by the highly selective monoallylation of 4,4 -dimethoxybenzhydrylamine (329). Deprotection of the allylated secondary amine 330 with 80% formic acid affords the primary ally-lamine 331. The reaction was applied to the total synthesis of gabaculine 332(203]. 

Primary and secondary amines react with acid halides to form amides. This reaction is a nucleophilic acyl substitution the replacement of a leaving group on a carbonyl carbon by a nucleophile. We will study nucleophilic acyl substitution in detail in Chapters 20 and 21. In this case, the amine replaces chloride ion. 

The secondary reduction of the terminal radical by Sml2 generates samarium alkyl species which are suitable for classical organometallic reactions, e.g. protonation, acylation, reactions with carbon dioxide, disulfides, diselenides, or the Eschenmoser salt. A broad variety of products is available (hydroxy-substituted alkanes, esters, carboxylic acids, thioethers, selenoethers, tertiary amines) by use of the double-redox four-step (reduction-radical reaction-reduction-anion reaction) route (Scheme 20) [73]. 

Three types of product can be obtained from the reaction of amines with carbon monoxide, depending on the catalyst. (1) Both primary and secondary amines react with CO in the presence of various catalysts [e.g., Cu(CN)2, Me3N-H2Se, rhodium or ruthenium complexes] to give V-substituted and V,A-disubstituted formamides, respectively. Primary aromatic amines react with ammonium formate to give the formamide. Tertiary amines react with CO and a palladium catalyst to give an amide. (2) Symmetrically substituted ureas can be prepared by treatment of a primary amine (or ammonia) with CO " in the presence of selenium or... 

PTC has been used efficiently for chlorination of dialkylphosphite and subsequent phosphorylation of secondary amines, O-alkylhydroxylamines, alcohols, etc. (Atherton-Todd reaction) via halophilic reaction with carbon tetrachloride ... 

Several peracetylated 2-deoxy-2-thioureido-P-D-glucopyranoses have been prepared by treating 2-deoxy-2-isothiocyanato-P-D-glucopyranose tetra-acetate with primary or secondary amines. Reaction of 2-amino-2-deoxy- D-glucopyranose tetra-acetate (184) with triphenylphosphine and carbon tetrachloride in dichloro-methane (the Appel reaction) gave the triphenylphosphonioamino salt (185), which yielded the phosphinimine (186) on treatment with triethylamine and the iV-methyl-aminotriphenylphosphonium iodide (187) on further treatment of (186) with... 

This [25] is an alternative method for determining the sum of primary and secondary amines, without distinguishing between them. The primary and secondary amines are converted to alkyl dithiocarbamic acids by reaction with carbon disulphide ... 

Primary amines cannot be usefully prepared, by reductive alkylation, from lower members of the aliphatic aldehydes and ammonia owing to side-reactions (for instance, formaldehyde and ammonia give hexamethylenetetramine). For aldehydes with more than five carbon atoms, however, conversion to the corresponding amine gives 60% yieldsEven better yields are reported for aromatic aldehydes, presumably because of the greater ease of imine formation With an excess of aromatic aldehyde the reaction with ammonia invariably leads to formation of the secondary amine but with aliphatic compounds a mixture of primary and secondary amines is generally obtained. Alternatively, secondary amines can be prepared directly from primary amines (equation 35). 

In the presence of ruthenium complexes, primary amines react with carbon dioxide at 120-140 °C to give Af,A -disubstituted symmetrical ureas Ruthenium complexes also catalyze the reaction of secondary amines with alkynes and carbon dioxide to give vinyl carbamates". ... 

This disappointing result is unfortunately quite neral. Secondary amines react with crown ether acid chlorides to give N-alkyl amides, but the slower reaction with crown ether anhydrides results in much poorer yields and significant competing epimerization via deprotonation-ieprotonation at the carbon adjacent to the carboxylic acid. The monoamide-triadd (above R-H) can be prepared from the corresponding primary amino-alcohol. The more reactive amine steers the dominant reaction towards amide formation without epimerization. 

The condensation of aldehydes or ketones with secondary amines leads to "encunines via N-hemiacetals and immonium hydroxides, when the water is removed. In these conjugated systems electron density and nudeophilicity are largely transferred from the nitrogen to the a-carbon atom, and thus enamines are useful electroneutral d -reagents (G.A. Cook, 1969 S.F. Dyke, 1973). A bulky heterocyclic substituent supports regio- and stereoselective reactions. 

There also exists an acidregioselective condensation of the aldol type, namely the Mannich reaction (B. Reichert, 1959 H. Hellmann, 1960 see also p. 291f.). The condensation of secondary amines with aldehydes yields Immonium salts, which react with ketones to give 3-amino ketones (=Mannich bases). Ketones with two enolizable CHj-groupings may form 1,5-diamino-3-pentanones, but monosubstitution products can always be obtained in high yield. Unsymmetrical ketones react preferentially at the most highly substituted carbon atom. Sterical hindrance can reverse this regioselectivity. Thermal elimination of amines leads to the a,)3-unsaturated ketone. Another efficient pathway to vinyl ketones starts with the addition of terminal alkynes to immonium salts. On mercury(ll) catalyzed hydration the product is converted to the Mannich base (H. Smith, 1964). 

Amines are powerful nucleophiles which react under neutral or slightly basic conditions with several electron-accepting carbon reagents. The reaction of alkyl halides with amines is useful for the preparation of tertiary amines or quaternary ammonium salts. The conversion of primary amines into secondary amines is usually not feasible since the secondary amine tends towards further alkylation. 

The reaction of a vinyl ether with carbon dioxide and a secondary amine gives a carbamic ester (246). 

Phosgene reacts with a multitude of nitrogen, oxygen, sulfur, and carbon centers. Reaction with primary alkyl and aryl amines yield carbamoyl chlorides which are readily dehydrohalogenated to isocyanates. Secondary amines also form carbamoyl chlorides. 

These Br nsted-type plots often seem to be scatter diagrams until the points are collated into groups related by specific structural features. Thus, p-nitrophenyl acetate gives four separate, but parallel, lines for reactions with pyridines, anilines, imidazoles, and oxygen nucleophiles.Figure 7-4 shows such a plot for the reaction of trans-cmmm c anhydride with primary and secondary aliphatic amines to give substituted cinnamamides.All of the primary amines without substituents on the a carbon (R-CHi-NHi) fall on a line of slope 0.62 cyclopentylamine also lies on this line. If this line is characteristic of normal behavior, most of the deviations become qualitatively explicable. The line drawn through the secondary amines (slope 1.98) connects amines with the structure R-CHi-NH-CHi-R. The different steric requirements in the acylation reaction and in the model process... 

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