N-monoalkylation

The selective N-monoalkylation of anilines with alkyl halides and alkyl tosylates under microwave irradiation has been described by Romera and coworkers (Scheme... 

Molybdenum trioxide acrolein formation, 30 152 allyl iodide reactions, 30 150 azopropene reactions, 30 150 Molybdenyl compounds, M=0 bond, 31 125 N-Monoalkylation, aniline derivatives, 38 249-252... 

Recently, isocyanides were employed in the synthesis of N-monoalkyl pyranopyrazoles, difficult to obtain by other methods (08JCR222,09X3492) (Scheme 76). 

Bei dcr N-Alkylierung von primaren Aminen mit Alkoholen konnen je nach Bedingungen neben den N-Monoalkyl-Derivaten auch N,N-Dialkyl-Derivate entstehen letztere konnen sogar zu den Hauptprodukten werden. Diese Verhaltnisse sind fur die N-Alkylierung von Anilin und C-substituierten Anilinen mit Alkoholen (UberschuB) in Gegenwart von Di-chloro-tris-[triphenylphosphan]-ruthcnium(II) eingehend untersucht worden2. 

Treatment of a primary amine with an equimolar amount of an alkylating agent and a base generally produces a mixture of an N-monoalkylated amine (1) and an N,N-dialkylated amine (2) (2/). However, the cooperative function of weakly acidic and weakly basic sites on zeolites, together with steric demands by the zeolite cavities, brought about selective N-monoalkylation of... 

In opposition to the preceding case, the reaction of phenoxides anions with 1-chloroalkyl-N-monoalkyl carbamates leads to acylation instead of alkylation as shown in scheme 137. 

N-Monosubstituted anudosulfonyl chlorides,5 N-Monoalkyl amidosulfonyl chlorides are obtained conveniently and in high yield by the reaction of an alkylamine hydrochloride with sulfuryl chloride in refluxing acetonitrile in the presence of a Lewis acid such as antimony(V) chloride. 

High silica aluminosilicates [ZSM-5(250)] favor N-monoalkylated products compared to aluminophosphates. 

With a primary amine such as n-octylamine, we observe at low conversion (8 %) high selectivity for the N-monoalkylated product whereas 90 % N,N-dimethylated amine are formed at high conversion (94 %). In reductive alkylation, it is even more difficult to obtain the monomethylated product selectively. For example, in the Eschweiler Clarke procedure [17], only the dimethylated amine is formed, even with an amine-to-formaldehyde ratio of 1. In the Hofmann-type reaction, a mixture of mono- and dimethylamine with the corresponding trimethylammonium salt is generally produced. 

The procedure described above illustrates a general, two-step method for the preparation of secondary or tertiary amines. It can be considered as a reductive N-alkylation of a nitrile or an N-monoalkylation of a primary or secondary amine. The first step in the procedure involves direct addition of an aliphatic amine to a nitrile promoted by a stoichiometric amount of cuprous chloride, as fully described recently.4 This method may be used with a large variety of nitriles and primary or secondary aliphatic amines. The nitrile itself may be used as solvent (acetonitrile, benzonitrile). In the case of a primary amine, substrate stoichiometry must be adapted to obtain selectively either the N-monosubstituted amidine [1 eq amine, 1.2 eq Cu(l)CI in acetonitrile] or the N,N-disubstituted amidine [4 eq amine, 1 eq Cu(l)CI, 1 eq acetonitrile in alcohol or DMSO].4... 

Uber die wenigen bekannten Beispiele einer direkten O-Acylierung von N-Monoalkyl-hydroxylaminen, aus denen durch N-Acylierung Hydroxamsauren erhalten werden, (s.S. 1312) ist bereits ausfuhrlich im Bd. X/l, S. 1231 (1971) berichtet worden. 

This method can also be used for N-monoalkylation by use of a 1 1 mole ratio of amine and aldehyde. 

IsowA, Y., and H. Kurita A New Reagent for the Syntheses of N-Monoalkylated Hydroxylamines N-Tosyl-0-2,4,6-trimethyl-benzylhydroxylamine. Bull. Chem. Soc. Japan 47, 720 (1974). 

The reaction products of N-monoalkyl-substituted p-phenylenedi-amines with alkyl isothiocyanates are proposed as effective antiozonants for rubber [260] ... 

---