From Secondary Amines

Af-(Diphenoxyphosphinylmethyl)-./V-(ethoxycarbonyl- and cyano-methybamines were reacted with EMME in boiling toluene under nitrogen for 16 hr to give aminomethylenemalonates (104) in 56 and 73% yields, respectively (84USP4444581, 84USP4444582). 

A-Cyclopropylanilines were reacted with EMME at 140-170°C for 2-25 hr to afford /V-cyclopropyl-/V-arylaminomethylenemalonates (109) in 68-72% yields [86JAP(K) 143363, 86JAP(K) 143364 87JAP(K)26272, 

3-Methylamino-6-morpholinopyridazine was reacted with EMME at 120°C for 2-3 hr to afford diethyl A-methyl-A-(6-morpholino-3-pyridazi-nyl)-aminomethylenemalonate in 54% yield (88JHC1535). 

The reaction of /V-(2,2,2-trifluoroethyl)-3,4-methylenedioxyaniline and EMME at 140-I50°C for 3 hr gave diethyl )V-(2,2,2-trifluoroethyI)-A(-(3,4-methylenedioxyphenyl)aminomethylenemalonate (76GEP2534869). N, N-Diphenylaminomethylenemalonates (112) were prepared from the reactions of diphenylamines and EMME at 190-210°C for 0.75-2.0 hr (69BRP1147336). 

2-Anilinoquinolines (113) were reacted with EMME to give N-(2-quinolinyl)-N-phenylaminomethylenemalonates (114) (87JIC481). 

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A -Nitroso derivatives, prepared from secondary amines and nitrous acid, are cleaved by reduction (H2/Raney Ni, EtOH, 28°, 3.5 h CuCl/concd. HCl"). Since many V-nitroso compounds are carcinogens, and because some racemization and cyclodehydration of V-nitroso derivatives of V-alkyl amino acids occur during peptide syntheses, V-nitroso derivatives are of limited value as protective groups. 

NaAlH2(0CH2CH20CH3)2, benzene or toluene, reflux, 20 h, 65-75% yield. Note that LiAlH4 does not cleave sulfonamides of primary amines those from secondary amines must be heated to 120°. 

Acid hydrolysis of (i-perfluoroalkylvinylamines, prepared from secondary amines and perfluoroalkylacetylenes, yields p-aminovinyl perfluoroalkyl ketones as the major products [79] (equation 20)... 

Extension of the hydration reaction to hydrogen peroxide has shown that stable peroxides are formed from enamines and the imonium salts derived from secondary amines and ketones (506,507). 

ZnBr2, CH2CI2, 89-94% yield. These conditions selectively cleave the BOC group from secondary amines in the presence of the primary deriva-... 

N,N Disubstituted thioureas from secondary amines and silicon tetra-isothiocyanate, 46, 69 N,N-Disubstituted ureas from secondary ammes and silicon tetraiso-cyanate, 46, 69... 

The color hues produced in the reaction do not appear to be affected by differing substituents at the amine nitrogen however electron-attracting substituents at the a-C atom appear to reduce the detection sensitivity of the reaction [1]. The colors produced remain stable for months in the dark. In the light the zones produced by primary amines fade more rapidly than those from secondary amines [1]. 

Although ultra accelerators or sulfur donors can be used together with primary accelerator (such as sulfenamide, TBBS) to improve cure rate as well as the heat resistance [16-18], their use is restricted because of the associated nitrosamine issue [19]. Accelerators derived from secondary amines, for example, MBS, TMTD, TETD, TMTM, and OTOS fall into this category. The combination of sulfenamide, such as CBS or TBBS, and a thiuram, such as TMTD or TETD, shows high-cure rates but suffers from the adverse effects on scorch resistance and vulcanizate dynamic property [20]. Additionally as previously mentioned, the use of TMTD or Tetraethylthiuram disulhde (TETD) or A-oxidiethylene dithiocarbamyl-A -oxidiethylene sulfenamide (OTOS) or 4,4 -Dithiodimorpholine (DTDM) is undesirable [21] due to concerns over carcinogenic nature of the A-nitrosamines formed from the parent amines. The solution to this originated by introduction of nitrosamine safe ultra accelerator such as TBzTD [22,23]. 

Iminium ions, generated in aqueous solution from secondary amines and formaldehyde, undergo a Barbier-type allylation mediated by tin, aluminum, and zinc. The reaction is catalyzed by copper and produces tertiary homoallylamines in up to 85% yield.67 The imines generated in situ from 2-pyridinecarboxaldehyde/2-quinolinecarboxaldehyde and aryl amines undergo indium-mediated Barbier allylation in aqueous media to provide homoallylic amines.68 Crotyl and cinnamyl bromides... 

No details are given for scheme A. Presumably one could use the phosphoryl chloride instead of the fluoride. Scheme B, in which ethyl chloride is formed, was run in boiling xylene using equimolar quantities of the reactants. Michaelis (33) has partially described the preparation of starting materials from secondary amines with phosphorus oxychloride and also ethyl dichlorophosphate. Schrader (38) obtained alkyl and amido fluophosphates by reaction of the corresponding chlorophosphates with sodium fluoride in aqueous or alcoholic solution. 

Amides prepared from secondary amines and acylchloride/imidazole,[391 carboxylic acid/oxalyldiimidazole,[41 ] carboxylic acid/sulfinyldiimidazole[61 ] or isolated imidazo-... 

A more recent report thoroughly investigates hydroaminomethylation of terminal alkenes to give high yields of linear (linear branched=99 1) tertiary amines from secondary amines and terminal alkenes or linear secondary... 

Dipolar cycloaddition reactions, of nitrones to olefins, 46, 97 of 3-phenylsydnone, 46, 98 Dispiro[5.1.5.1]tetradecane-7,14-dione, photolysis to cyclohexylidene-cyclohexane, 47, 34 preparation from cyclohexanecarbonyl chloride and triethylamine, 47, 34 Displacement of bromine from 1-bromo-2-fluoroheptane to give 2-fluoro-heptyl acetate, 46, 37 N,N -Disubstituted formamidines from triethyl orthoformate and primary amines, 46, 41 N,N-Disubstituted thioureas from secondary amines and silicon tetra-isothiocyanate, 45, 69 N,N-Disubstituted ureas from secondary amines and silicon tetraiso-cyanate, 45, 69... 

It is accepted that many widely used latex vulcanisation accelerators - dithiocaibamates, thiurams and thiazoles - are capable of producing Type IV allergic response in certain individuals within the population and may also possess increasingly unacceptable eco-toxic and acute toxicity profiles. Thiurams and dithiocaibamates (derived from secondary amines) can also produce potentially harmful N-nitrosamines. Four safer accelerators developed and commercialised by Robinson Brothers are described. They are designed to reduce or eliminate the impact of the above problems using sustainable technology. At the same time these accelerators produce equivalent technological performances to those conventionally used. 10 refs. 

Microorganisms have been shown to catalyze the formation of nitrosamines from secondary amines in the presence of nitrite (26). The amount of nitrosamine formed, however, increased as the basicity of the parent amine decreased, presumably due to the increase in the amount of unprotonated amine present (27). This reaction is especially important with respect to metalworking fluids since water-based fluids are inevitably contaminated by microbes and fungi. Microbes are thought to catalyze nitrosamine formation by lowering the pH of the medium or catalysis by one or more unidentified metabolic products. 

Electrophilic amination reactions by means of oxaziridines have been reviewed105. Cyclohexylidenehydrazines 86 are formed from secondary amines such as diethylamine, dibutylamine and morpholine and the spirooxaziridine 85105. 

A general method for the generation of aminyl radicals is by treatment of sulphenamides 340, prepared from secondary amines and A-benzenesulphenylphthalimide, with tributyltin hydride in the presence of AIBN (2,2/-azobisisobutyronitrile). The cyclopropyl derivative... 

FDMR has also been used to detect the transient radical cations formed from secondary amines by pulse radiolysis. As mentioned earlier this technique has been used to study a variety of systems such as the radical cation of triethylamine. The radical cations of diethylamine, n-propyl amine and f-butylamine, have also been studied25. The results have shown that the FDMR signal is enhanced with increasing alkyl substitution of the amine as in the pyrrolidines (18) and the piperidines (19)25. 

Nitrosamines, which are the amides of nitrous acid, are more stable and are derived from secondary amines with nitrous acid. iV-nitrosamides are substances which have a carbonyl group attached to a nitrogen-bearing NO group, e.g. iV-nitrosamides, iV-nitrosocarbamates and /V-nitrosoLireas see Figure 10. 

N,N-Disubstituted thioureas from secondary amines and silicon tetra-isothiocyanate, 46, 69... 

There is a distinct relationship between keto-enol tautomerism and the iminium-enamine interconversion it can be seen from the above scheme that enamines are actually nitrogen analogues of enols. Their chemical properties reflect this relationship. It also leads us to another reason why enamine formation is a property of secondary amines, whereas primary amines give imines with aldehydes and ketones (see Section 7.7.1). Enamines from primary amines would undergo rapid conversion into the more stable imine tautomers (compare enol and keto tautomers) this isomerization cannot occur with enamines from secondary amines, and such enamines are, therefore, stable. 

H2NO is a typical reactive intermediate endowed with short hfetime, aminoxyl radicals deriving from secondary amines may instead be stable whenever complying with the general structure 1 (R H), in which there are no hydrogens attached to the a-carbon atoms. 

The first example of anti-Markovnikov addition of O-nudeophiles to terminal alkynes was the catalytic addition of ammonium carbamates, generated in situ from secondary amines and carbon dioxide, to terminal alkynes, which regioselectively produced vinylcarbamates (Scheme 10.1) [5]. It was also the first time that a metal vinylidene was suggested as an active intermediate in catalysis [5]. 

The formation of vinylcarbamates is restricted to secondary amines and also to terminal alkynes, which is in line with the formation of a metal vinylidene intermediate. It is noteworthy that even starting from secondary amines, the presence of a hydroxy group in propargylic alcohols drove the reaction towards the formation of fi-keto carbamates, resulting from initial Markovnikov addition of the carbamate anion to the triple bond followed by intramolecular transesterification [10]. The proposed general catalytic cycle which applies for the formation of vinylic carbamates is shown in Scheme 10.2. 

Scheme 10.1 Selective formation of enol carbamates from secondary amines, CO2, and terminal alkynes.

FIGURE 100. Schematic representation of the stmctures of organomagnesium amides 255-263 derived from secondary amines... 

Secondary amines 268 are prepared using TBS-protected lithium amides 269 (Scheme 21), while the preparation of polyfunctional trlarylamines applies lithium amides which are derived from secondary amines. 

The reactions for the formation of nitrosamines from secondary amines is as follows ... 

When ammonia or primary amines are used, the product amines may participate in further aminomethylation, resulting in the formation of a mixture of amines. Other byproducts (aldehydes, alcohols, carboxamides) may also be formed. The reaction to produce tertiary amines from secondary amines, however, is fairly selective. Aminomethylation of ethylene with piperidine was reported to form /V-propyl-piperidine with 75% yield when the reaction was carried out in the presence of [Fe(CO)5] and water without an external source of CO (170°C, 14 h).207... 

Enamines are also potential ketones and accordingly have been used as the ketonic component in this type of pyrylium synthesis (63AG(E)394). The initial adducts, which form pyrylium salts on treatment with perchloric acid, are similar to those derived from secondary amines and pyrylium salts. The significant feature of this variant is that it gives access to pyrylium compounds which are unsubstituted at the 4- and 6-positions but which carry substituents at C-2 and C-5. More conventional enamines, such as 1-piperidinocyclohexene, afford bicyclic pyrylium salts (652), whilst polycyclic salts (653) result if cyclic chlorovinyl ketones are used. 

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