Amine with acetone, condensation

Aromatic amines, such as phenyl- -naphthylamine or condensation products of diphenylamine with acetone condensates, are excellent antioxidants and antiozonants but cause color development. From the sterically hindered phenols, monocyclic phenols, such as 2,6-di-teit-butyl-p-cresol, are less effective antioxidants but remain white and nontoxic during aging. They are, however, volatile and provide poor protection at elevated processing temperatures. Polycyclic phenols, such as 2,2 -methylene-bis (4-methyl-6-teit-butylphenol), are relatively nonvolatile, but become discolored by oxidation to a conjugated system. O Shea... 

Monomer dihydroquinolines, the production of which is difficult, are required for the synthesis of tetrahydroquinolines moreover, an expensive catalyst is needed for this process - crystalline iodine. L. P. Zalukaev et al. [70] proposed that sulfanilic acid be used as a catalyst for this purpose in the condensation of the amine with acetone. According to the data of the authors, the addition of 1-2% sulfanilic acid to the reaction mass makes it possible to direct the reaction toward the formation of a large amovmt of the monomer, readily isolated by vacuum distillation. 

The reactions of nickel(II) and copper(II) amino complexes with acetone have been studied extensively. Condensation reactions of coordinated amines with acetone proceed relatively easily, but further reactions follow. The initially formed complexes, which contain Schiff bases, undergo intramolecular rearrangements to form complexes containing macrocyclic ligands. Scheme 11.15. This reaction is the basis for the synthesis of a large number of macrocyclic ligands. 

Other Rea.ctlons, The anhydride of neopentanoic acid, neopentanoyl anhydride [1538-75-6] can be made by the reaction of neopentanoic acid with acetic anhydride (25). The reaction of neopentanoic acid with acetone using various catalysts, such as titanium dioxide (26) or 2irconium oxide (27), gives 3,3-dimethyl-2-butanone [75-97-8] commonly referred to as pinacolone. Other routes to pinacolone include the reaction of pivaloyl chloride [3282-30-2] with Grignard reagents (28) and the condensation of neopentanoic acid with acetic acid using a rare-earth oxide catalyst (29). Amides of neopentanoic acid can be prepared direcdy from the acid, from the acid chloride, or from esters, using primary or secondary amines. 

Reaction of p-chloroaniline with dicyanamide affords the biguan-ide, 182. This is condensed immediately with acetone to form the aminal cycloguanil (183). The compound is usually used as a salt with pamoic acid (184). 

Oxidation of primary amines with DMD or other oxidants leads to the formation of a complex mixture of nitroso, oximes, and nitro compounds (76). Utilization of DMD in acetone affords dimethyl nitrone (22). This is likely to be a result of the initial oxidation of primary amine (19) to hydroxylamine (20) with the subsequent condensation of acetone and oxidation of imine (21) (Scheme 2.9) (77). 

Preparative applications have been found with the anhydrous bis-hy-drochlorides of various o-phenylenediamines 46. These were produced at the 50-g scale and all of these were required for enabling gas-solid condensation reactions with acetone [5]. If the monohydrochlorides of the o-phenylenedi-amines are required, the dihydrochlorides 47 are simply milled with a stoichiometric amount of the corresponding free solid diamine 46 in order to get... 

One other synthesis of a A3-oxadiazoline was obtained unintentionally. Hull and Farrand114 refluxed cyanamide and phenylhydroxyl-amine in acetone expecting to obtain the disubstituted hydroxylamine (23). Instead, the solvent acetone had condensed with the hypothetical... 

Metal template syntheses of complexes incorporating the p-amino imine fragment have been introduced by Curtis as a result of his discovery that tris(l,2-diaminoethane)nickel(II) perchlorate reacted slowly with acetone to yield the macrocyclic complexes (40) and (41) (equation 8).81-83 In this macrocyclic structure the bridging group is diacetone amine imine, arising from the aldol condensation of two acetone molecules. This reaction is widely general, in the same way that the aldol reaction is, and can be applied to many types of amine complexes. The subject has been reviewed in detail with respect to macrocyclic complexes by Curtis.84... 

The synthesis of 2,2-dimethylsuccinic acid (Expt 5.135) provides a further variant of the synthetic utility of the Knoevenagel-Michael reaction sequence. Ketones (e.g. acetone) do not readily undergo Knoevenagel reactions with malonic esters, but will condense readily in the presence of secondary amines with the more reactive ethyl cyanoacetate to give an a, /f-unsaturated cyanoester (e.g. 15). When treated with ethanolic potassium cyanide the cyanoester (15) undergoes addition of cyanide ion in the Michael manner to give a dicyanoester (16) which on hydrolysis and decarboxylation affords 2,2-dimethylsuccinic acid. 

Other alkylation reactions are observed in the condensation of cyclo-propanium ions (generated in situ) with ketones 89.92)> enamines6, nitroalkanes 93>, dimethylmalonate 92>, and phenol. 92> Thus, 7-hydroxy-7-pyrrolidinobicyclo[4.1.0]heptane (56) as well as the 7,7-dipyrrolidino derivative (54) react with acetone to give the amino ketone 113. 89> This reaction may be pictured as an addition of the enol form of the ketone to the reactive iminium salt formed from the carbinol amine. In like manner, phenol undergoes ortho substitution with the carbinol amine 114 formed from cyclopropanone and dimethyl amine. 

The most common template syntheses have been for macrocycles containing the donor atoms in the ratio of 2 2, e.g., reaction of the Ni(II) complexes (LXXXV), formed by condensation of oc-diketones with /i-mercaptoamines in the presence of Ni(II) ions, with a,a -dibromo-o-xylene affords LXXXVI through a kinetic template effect (see Section II,A) (136-138). Reaction with acetone links the coordinated amine groups of dithiodiamine to form the macrocycle complex LXXXVII (23). 

Interest in these ligands stems from a desire to synthesize improved analogues of the cobalamines 100). With this in mind, 2,6-diacetylpyridine was condensed with N,N,N- f ra(aminopropyl)amine in the presence of nickel(II) or eopper(II) to afford the complex of 105, Cobalt(II) and zinc(II) have also been employed as templating agents in the synthesis of 105 101). The reaction of the nickel(II) complex of 105 with acetone results in a dimeric complex, 106101), by a process that is well established for primary amines 102). 

Related reactions include the formation of the 2-cyano compounds (190) when 1,2-dimethyl-5-nitroimidazole is heated with nitrosyl chloride or an AT-oxide, and when 2-methyl-l-(o-nitrophenyl)imidazoles (191) cyclize under the influence of iron(II) oxalate (Scheme 98) (74JCS(P1)1970). The last reaction product is contaminated by a large amount of amine reduction product ( 64%) but there is also some cyclization with the 4-methyl isomer of (191). In the presence of trimethylamine, 2-cyanomethylbenzimidazole condenses with acetone to give the unsaturated derivative (192 Scheme 99) (77CPB3087). Neither 2-methylimidazole nor 2-methylbenzimidazole reacts with formamide in the presence of phosphoryl chloride. 

The azomethine ylide must be formed from the amino acid and acetone. Briefly, the amine condenses with acetone to give an iminium ion. Decarboxylation produces the 1,3-dipole, which can undergo [3 + 2] cycloaddition to C60 to give the observed product. By now you should be able to draw a mechanism for formation of the iminium ion. 

Holmstedt et al. found that terminal primary amines condense readily with acetone, therefore a phenolic amine (serotonine) gives the corresponding trimethyl silyl ether-acetone condensation product when silylation is carried out in acetone solution. Primary amines may be entirely lost on a NGS column, but the acetone condensation products have a normal behaviour under these conditions. The relative retention times for indole bases related to tryptamine are summarized in Table 17.1. 

Procedure Amines, 10-1000 jug, were acetylated by treatment with 10-20 All of redistilled acetic anhydride and 10-20 /rl of pyridine (distilled over potassium hydroxide). Excess reagents were removed in a vacuum desiccator. Methyl esters of amine acids were prepared by refluxing in methanolic hydrogen chloride. iV-Acetylation of these esters was by treatment with acetic anhydride and pyridine. Esterification of other acids was carried out with diazomethane in ether. The products were dissolved in ethyl acetate, and volumes of 0.1 to 2 ju.1 were injected into the gas chromatograph. Amounts of sample injected were about 0.1 jitg for rapidly eluted compounds and 1 p,g for those with long retention times. In some cases, acetone condensation products of the primary amines were chromatographed. Catecholamines, however, underwent decomposition under these conditions. 

Fia. 15. Separation of tryptamine-related indole bases. The compounds are N,N-dimethyltiyptamine (DMT), eneamine (acetone condensation product) from tiypt-amine (TRYPT-SB), 7-trimethylsilyloxy-JV,iV-dimethyltryptamine (7-OH-DMT-TMSi), 4-trimethylsilyloxy-iV,i r-dimethyltryptaniine (4-OH-DMT-TMSi), 5-tri-methylsilyloxy-iV,JV-dimethyltryptamine (5-OH-DMT-TMSi), 6-trimethylsUyloxy-JV, iV -dimethyltryptamine (6-OH-DMT-TMSi), and the eneamine (acetone condensation product) from 5-trimethylsilyloxytryptamine (5-OH-TRYPT-TMSi-SB). Conditions 7% F-60, 1% EGSS-Z, on 100-120-mesh Gas Chrom P, 182 C, 18 psi argon ionization detection system. Reproduced from Homing et al. (H15), with permission. 

Compounds of formula 63 are readily cyclized by reduction of the nitro group with Raney nickel and hydrogen. The amine thus formed condenses intramolecularly, with the carbonyl function providing the 3,4-dihydro system 64. This may be smoothly oxidized with iodine or an acetone solution of potassium permanganate. " " This route has been used for the unambiguous synthesis of compounds 65, 66, 67, and 68 48.49 Qf particular interest are compounds 66 and 67, which have been used to confirm the orientation of products from the reaction of polyaminopyridines with pyruvaldehyde and p-chlorophenylglyoxal. ... 

Robinson s synthesis of tropine (210) on the other hand was as direct (two steps) as Willstatter s was long but it involved the use of the very sensitive succinic dialdehyde (from pyrrole) (157, 219). The fragments from the hypothetical fission of the symmetrical tropinone (XLVI) suggested to Robinson the possibility of obtaining this ketone by the condensation of succinic dialdehyde and methylamine with acetone. The primary reaction was considered to be the combination of succinic dialdehyde with methyl-amine and the resulting biscarbinolamine (XLIX) in turn condensed with acetone. This synthesis was realized when these reactants, in aqueous... 

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