N-Alkyl Derivatives

The amide group is readily hydrolyzed to acrylic acid, and this reaction is kinetically faster in base than in acid solutions (5,32,33). However, hydrolysis of N-alkyl derivatives proceeds at slower rates. The presence of an electron-with-drawing group on nitrogen not only facilitates hydrolysis but also affects the polymerization behavior of these derivatives (34,35). With concentrated sulfuric acid, acrylamide forms acrylamide sulfate salt, the intermediate of the former sulfuric acid process for producing acrylamide commercially. Further reaction of the salt with alcohols produces acrylate esters (5). In strongly alkaline anhydrous solutions a potassium salt can be formed by reaction with potassium / /-butoxide in tert-huty alcohol at room temperature (36). 

Aminotriazole is carboxylated at the 5-position by heating with aqueous sodium bicarbonate in a Kolbe-type reaction (7lJCS(C)l50l). 2-Thiazolinones undergo the Gatter-mann and Reimer-Tiemann reactions at the 4-position, and 3- and 4-pyrazolinone anions on alkylation give 4-alkyl as well as O- and N-alkyl derivatives. 

Similar procedures have been used in preparing other 2-alkylaminoethanols and N-alkyl derivatives of l-amino-2-pro-panol, 2-amino-l-propanol, 3-amino-l-propanol, 2-amino-l-bu-tanol, and l-amino 2-methyl-2-propanol. ... 

There has been considerable interest recently in the quatemization of purine compounds, although most of those examined have contained hydroxyl or amino substituents and therefore products may be regarded as the acid salts of N-alkylated derivatives. 

Analog den Pyridinen, Chinolinen usw. werden auch die entsprechenden N-Alkyl-Derivate im Heteroaromaten-Kern hydriert. So erhalt man z. B. aus 3-Hydroxy-4-me-thyl-pyridinium-methylsulfat u. a. 3-Hydroxy-1 - methyl-pip eridin (20%igc Schwefelsau-re/Blei-Kathode geteilte Zelle)2. 

N-Alkyl-Derivate des 2,2-Dichlor-3-oxo-butansaure-amids lassen sich im kg-MaB-stabe bei niedrigen Potentialen selektiv zu 2-Chlor-3-oxo-butansaure-alkylamiden reduzieren8 ... 

The Schiff reaction between chitosan and aldehydes or ketones yields the corresponding aldimines and ketimines, which are converted to N-alkyl derivatives upon hydrogenation with borohydride. Chitosan acetate salt can be converted into chitin upon heating [130]. The following are important examples of modified chitosans that currently have niche markets or prominent places in advanced research. 

Amides are very weak nucleophiles, far too weak to attack alkyl halides, so they must first be converted to their conjugate bases. By this method, unsubstituted amides can be converted to N-substituted, or N-substituted to N,N-disubstituted, amides. Esters of sulfuric or sulfonic acids can also be substrates. Tertiary substrates give elimination. O-Alkylation is at times a side reaction. Both amides and sulfonamides have been alkylated under phase-transfer conditions. Lactams can be alkylated using similar procedures. Ethyl pyroglutamate (5-carboethoxy 2-pyrrolidinone) and related lactams were converted to N-alkyl derivatives via treatment with NaH (short contact time) followed by addition of the halide. 2-Pyrrolidinone derivatives can be alkylated using a similar procedure. Lactams can be reductively alkylated using aldehydes under catalytic hydrogenation... 

Moncrief summarized the work of Cohn and the information in the early literature. As early as 1923, it was known that rupture of the heterocyclic ring, as well as substitution of the imino hydrogen atom, results in the loss of sweetness. Thus, o-carboxybenzenesulfonamide and N-alkyl derivatives of saccharin are tasteless. This loss of sweetness would be expected, as the NH group is the only proton-donor function available in the molecule. 

The first sample, dating from the Ptolemaic period ( 300 BC), was found in a container from a tomb from Fayoum. The volatile compounds observed in this sample (see Table 10.1, column 11) were very similar to those of pine pitch. The two chromatograms are presented in Figure 10.21. The major compounds are guaiacol (11) and its para-n-alkyl derivatives (24, 35, 43) and the degradation products of diterpenic acids 19-norabieta-8,l 1,13-triene (95), 18-norabieta-8,11,13-triene (100), 10,18-bisnorabieta-5,7,9(10),ll,13-pentaene (102), retene (105) and methyldehydroabietate (106). The major compounds observed after... 

Ir-PN catalysts which are quite effective for N-aryl imines also show some promise for N-alkyl derivatives. Of special interest were the high TOF claimed for the Ir-L4 system, but unfortunately the ee is very low (entry 4.5). Several other Ir-PN were described with moderate to good ee-values, but again the TON and TOF were modest, as shown (Table 34.4 entry 4.6 (see also [49]). 

Derivatives of diaminoanthrarufin (3.77 X = Y = H) and its 1,8-dihydroxy-4,5-diamino isomer (diaminochrysazin) have been among the most widely used anthraquinone dyes for ester fibres. For example, methylation of diaminoanthrarufin gives Cl Disperse Blue 26, a mixture of several components. Study of the pure N-alkylated derivatives from the base confirmed that monosubstitution (3.77 X = H, Y = alkyl) gives mid-blue dyes with excellent dyeing properties and acceptable fastness on polyester, but the bis-alkyl dyes (3.77 X = Y = alkyl) are greener and inferior in application properties. Mixtures of the unsubstituted base with alkylated components, as obtained industrially, were especially advantageous for build-up to heavy depths, however [93]. 

The anticonvulsant agent primidone (4.246) is the 2-dihydro derivative of phenobarbital (4.247), which is one of its metabolites. The second major metabolite, 2-ethyl-2-phenylmalondiamide (4.248), is produced by a double C-N cleavage [160]. The profile of plasma levels in rats strongly suggests that 2-ethyl-2-phenylmalondiamide is not derived from the metabolite phenobarbital, but directly from primidone. Indeed, a C(2)-hydroxylated metabolite serves as an intermediate for both detected metabolites (see also Chapt. 6 in [21]). N-Alkyl derivatives of primidone yield a greater proportion of ring-opened metabolites, an observation explained by their higher susceptibility to oxidative metabolism at C(2) [161]. 

Danikiewicz, W. Ortho Interactions During Fragmentation of N- 2-Nitrophenyl)methanesulfonamide and Its N-Alkyl Derivatives Upon Electron Ionization. Eur. Mass Spectrom. 1997, 3, 209-216. 

Synthesis of Lipophilic Arabinofuranosyl Cytosine N" -Alkyl Derivatives and Heterodinucleoside Phosphate Duplex Drugs... 

Schwendener RA, et al. Antitumor activity and pharmacological properties of orally administered lipophilic N" -alkyl derivatives of 1-P-D-arabinofuranosylcy-tosine (ara-C). J Cancer Res Clin Oncol 1996 122 102. 

The simplest systems, and most closely related to the open chain systems discussed in the preceding section, are cyclic amidines, such as 2-iminopyrrolidine ([55], n = 3), 2-iminopiperidine ([55],n = 4) and their N-alkyl derivatives. Infrared spectra of their hydrochloride... 

Reactivity studies on the iminophosphoranes have revealed that N-alkyl derivatives show a higher reactivity than A-aryl or A-vinyl derivatives. The order of reactivity of the heterocumulenes shown in Scheme 33 is given in Scheme 34 (21HCA861). 

N-Alkylated derivatives could be obtained by catalytic reductive amination from a mixture of D-fagomine, or its linear precursor, and the corresponding aldehyde. 

The synthesis of compound 135 (Scheme 12) includes the production of isoquinoline 132 via a Bischler-Napieralski reaction, its reduction and alkylation on the nitrogen atom followed by cyclization of N-alkyl derivatives 134 in the presence of acids (83JHC1477 Scheme 36). 

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