V-Alkylation

V-Alkylation can also be carried out with the appropriate alkyl haUde or alkyl sulfate. Reaction of aniline with ethylene, in the presence of metallic sodium supported on an inert carrier such as carbon or alumina, at high temperature and pressure yields V/-ethyl- or /V,/V-diethylaniline (11). At pressures below 10 MPa (100 atm), the monosubstituted product predominates. 

Catalytic alkylation of aniline with diethyl ether, in the presence of mixed metal oxide catalysts, preferably titanium dioxide in combination with molybdenum oxide and/or ferric oxide, gives 63% V/-alkylation and 12% ring alkylation (14). 

MonoaLkylation using small alkyl groups of the 1-, 2 - and 3 -amines tends to reduce potency somewhat, whereas alkylation of the 3-amino group reduces activity considerably (147). 1-/V-Alkylation, as in the case of 1-A[-acylation, can lead to resistance to some bacterial resistance reactions, eg,... 

Excellent yields of the former product are also obtained with quinoline N-oxide. Improved yields of Reissert compounds are found under phase-transfer conditions (29). The regiochemistry of the method changes dramatically with /V-alkyl quin olinium salts, eg, /V-methy1quino1inium iodide [3947-76-0] (12), which form 4-cyanoquinoline [23395-72-4] (13) (30), through the intermediary in this example of A[-methyl-4-cyano-l,4-dihydroquinoline... 

Protection Against Flex Cracking. Most antioxidants including waxes provide oxidation protection under static conditions. However, most of them are not effective in mbber products subjected to dynamic flexing, eg, sidewall compounds in tires. The best dynamic protection is provided by either /V-alkyl-/V-phenyl or diaryl-/)-phenylene diamines. 

V-Alkyl or A/-aryl succinimides can be prepared from the corresponding amines (107) or from succinic anhydride, ammonia, and the corresponding alcohol (108). Succinimides are also obtained by vapor-phase hydrogenation of the corresponding maleimides ia the presence of a catalyst (109). 

The /V-alkyl-/V-aryl- -PDAs (where the aryl is phenyl and the alkyl may be cyclohexyl, 1,3-dimethylbutyl or 1-methylethyl) ate the most widely used /)-PDAs. These derivatives reduce the rate of crack growth and also the number of cracks. The alkyl-aryl- -PDAs are in general excellent antiozonants, particularly in dynamic environments. These derivatives are destroyed only slowly by oxygen and increase the scorchiness of the stock only slightly. These are intermediate in staining among the three classes of -PDAs. 

The N,]S -dialkyl-/)-PDAs are manufactured by reductively alkylating -PDA with ketones. Alternatively, these compounds can be prepared from the ketone and -lutroaruline with catalytic hydrogenation. The /V-alkyl-/V-aryl- -PDAs are made by reductively alkylating -nitro-, -nitroso-, or /)-aminodipheny1 amine with ketones. The AijAT-dialkyl- PDAs are made by condensing various anilines with hydroquinone in the presence of an acid catalyst (see Amines-aromatic,phenylenediamines). 

V-Alkyl and A/-aryl substituted naphthyl amines are also important, eg, letter acid derivatives, but are usually manufactured by the Bucherer reaction. 

There are only few reactions known introducing substituents to the H-bearing nitrogen of oxaziridines. (V-Alkylation of l-oxa-2-azaspiro[2.5]octane (3,3-pentamethylene-oxaziridine 52) with r-butyl chloride to give (53) was carried out for structure proof of (52). This reaction is of no preparative importance, since N-alkylated oxaziridines are easily obtained by ring synthesis. 

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. 

Tertiary p2/ -V-alkyl-l,2,3,4-tetrahydro-j8- and -y-carboline derivatives can be quaternized at the same site to give 2,2-dialkyl-l,2,3,4-tetrahydro-j8- and -y-carbolinium... 

Treatment of 2- 5//-dibenz[i>,/]azepin-5-yl acetaldehyde (16), prepared in 68% yield by /V-alkylation of 5/7-dibenz[A,/]azepine with bromoacetaldehyde diethyl acetal followed by acid hydrolysis, with methyl hydroxylamine yields the isolable nitrone 17, which in refluxing toluene undergoes intramolecular 1,3-dipolar cycloaddition at the CIO —Cl 1 alkene bond to give 2,3,3a, 12b-tetrahydro-2-methyl-3,8-methano-8//-dibenz[i>,/]isoxazolo[4,5-r/]azepine (18).235... 

A methanolic solution of a V-alkyl-2-nitroaniline (13.3 mmol) was hydrogenated at 20 C and atmospheric pressure in the presence of Raney nickel, filtered and treated with coned HCI (1.32 mL, 13.3 mmol), followed by sodium dicyanimide (1.17 g, 13.1 mmol) in H20 (5 mL). The mixture was heated in an open vessel on a steam bath for 1 h, by which time most of the McOH had evaporated. The resulting suspension of a black oil was treated with a solution of picric acid (6.0 g, 26.2 mmol) in MeOH, whereupon the dipicrate of the product separated as yellow crystals. 

Hydantoin 9 has also been used as a heterocyclic starting material for glyphosate via interme ate 10 (14). Similarly, the phosphonomethylation of 3-V-alkyl hydantoins produced the corresponding unsymmetrically substituted cyclic analogs (14). 

Another catalytic application emanating from the Hieber base reaction was developed by Reppe and Vetter [108]. They showed that 1-propanol 126 could be generated by treatment of ethylene 125 with catalytic amounts of Fe(CO)5 78 under CO-pressure and basic reaction conditions (Scheme 33). Thereby, trimethylamine and V-alkylated amino acid derivatives mrned out to be optimal bases for this reaction. Like ethylene 125, propylene could be transferred mainly to 1-butanol diolefins like butadiene only reacted to monoalcohols. By employing these reaction conditions to olefins in the presence of ammonia, primary or secondary amines, mono-, di-, and trialkylamines were obtained whose alkyl chains were elongated with one carbon atom, compared to the olefins. 

Oxazolium oxides can also be made by (V-alkylation of oxazolinones.145... 

This chapter covers recent information on the preparation, physical properties, and reactions of quinoxaline and its C-alkyl, C-aryl, /V-alkyl, and A-aryl derivatives as well as their respective ring-reduced analogs. In addition, it includes methods for introducing alkyl or aryl groups (substituted or otherwise) into quinoxalines already bearing substituents and the reactions specific to the alkyl or aryl groups in such compounds. For simplicity, the term alkylquinoxaline in this chapter is intended to include alkyl-, alkenyl-, alkynyl-, and aralkylquinoxalines likewise, arylquino-xaline includes both aryl- and heteroarylquinoxalines. 

Although /V-alkyl- and /V-arylpiperazines abound in the pyrazine literature,1059 the corresponding reduced quinoxalines are rarely encountered. However, reductive alkylation of quinoxaline gave products such as l,4-diethyl-l,2,3,4-tetrahydroqui-noxaline (see Section 2.1.3), and several other typical preparative routes are illustrated in the following examples. 

It seems likely that direct alkylation of a tautomeric quinoxalinone invariably gives a mixture of O- and /V-alkylated products in which the more soluble... 

Quinoxalinones are usually rendered nontautomeric (fixed) by (V-alkylation, but (V-acylation or the like can occasionally serve the same purpose. 

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