Amines, cyclic

Cyclic amines (referred to as imines) are polymerized by acids and other cationic initiators [Goethals, 1984, 1989a,b Hauser, 1969 Kubisa, 1996 Tomalia and Killat, 1985]. The 3-membered imines (IUPAC aziridines) are the most studied of the cyclic amines. Polyethy-leneimine [IUPAC name poly(iminoethylene)] had been commercially available and used in the treatment of paper and textiles. It is no longer available in the United States because of the high toxicity of the monomer. 

Polyethyleneimine is also extensively cyclized as a result of intramolecular nucleophilic attack of primary and secondary amines on the iminium group. This results in cyclic oligomer as well as polymer molecules containing large-sized rings as part of their structure. 

Substitution on the aziridine ring hinders polymerization [Baklouti et al., 1989 Van de Velde, 1986]. The 1,2- and 2,3-disubstituted aziridines do not polymerize 1-and 2-substituted aziridines undergo polymerization, but the yield of polymer relative to low-molecular-weight linear and cyclic oligomers and the molecular weight of the polymer depend on the substituent (both electronic and steric effects are important). 

Cationic polymerization of 4-membered imines (IUPAC azetidines) generally follows the same patterns as the aziridines [Matyjaszewski, 1984a,b Muhlbach and Schulz, 1988]. Imines are generally unreactive toward anionic polymerization presumably because of the instability of an amine anion (which would constitute the propagating species). The exception occurs with V-acylaziridines as a result of the electron deficiency of the nitrogen coupled with the highly strained 3-membered ring. 

Piperidine likewise shows a strong molecular ion and M - 1 (base) peak. Ring opening followed by several available sequences leads to characteristic peaks at m/z 70, 57, 56, 44, 43, 42, 30, 29, and 28. Substituents are cleaved from the ring (rule 6, Section 2.7). 

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Luminescence has been used in conjunction with flow cells to detect electro-generated intennediates downstream of the electrode. The teclmique lends itself especially to the investigation of photoelectrochemical processes, since it can yield mfonnation about excited states of reactive species and their lifetimes. It has become an attractive detection method for various organic and inorganic compounds, and highly sensitive assays for several clinically important analytes such as oxalate, NADH, amino acids and various aliphatic and cyclic amines have been developed. It has also found use in microelectrode fundamental studies in low-dielectric-constant organic solvents. 

In Diels-Alder reactions a nitroolefin may function as an electron-deficient ene com-onent or a 1,2-dihydropyridine derivative may be used as a diene component. Both types of iactants often yield cyclic amine precursors in highly stereoselective manner (R.K. Hill, 1962 i. BOchi, 1965, 1966A). 

The reaction of the vinylcyclopropanedicarboxylate 301 with amines affords an allylic amine via the 7r-allylpalladium complex 302[50]. Similarly, three-membered ring A -tosyl-2-(l,3-butadienyl)aziridine (303) and the four-mem-bered ring azetidine 304 can be rearranged to the five- and six-membered ring unsaturated cyclic amines[183]. 

Allylic amines can be cleaved. Hydrogenolysis of allylic amines of different stereochemistry with NaBH CN was applied to the preparation of both dia-stereoisomers 655 and 657 of cyclopentenylglycine from the cyclic amines 654 and 656 of different stereochemistry[405]. 

Amines normally have no effect on the isothiazole ring, but 3-chloro-4-nitroisothiazole (49) reacts with cyclic amines such as morpholine at 0 °C to give the enamine (50) (75JOC955). The mechanism may involve attack either at sulfur or at the 5-position (Scheme 6). 

Photoelectron spectroscopic studies show that the first ionization potential (lone pair electrons) for cyclic amines falls in the order aziridine (9.85 eV) > azetidine (9.04) > pyrrolidine (8.77) >piperidine (8.64), reflecting a decrease in lone pair 5-character in the series. This correlates well with the relative vapour phase basicities determined by ion cyclotron resonance, but not with basicity in aqueous solution, where azetidine (p/iTa 11.29) appears more basic than pyrrolidine (11.27) or piperidine (11.22). Clearly, solvation effects influence basicity (74JA288). 

In aqueous solution, azetidine (p/sTa 11.29) is slightly more basic than pyrrolidine and larger-ring cyclic amines and appreciably more basic than aziridine. It forms an addition compound (m.p. - 9 to -6 °C) with trimethylboron which is more stable than that formed by pyrrolidine (50JA2926, 64HC(l9-2)885). Azetidinium salts are well known (Section 5.09.2.2.7). 

Polymers have also been prepared from cyclic amines such as piperazine and bis-(p-aminocyclohexyl)methane. An early copolymer, Igamid 1C, was based on the latter amine. This amine is also condensed with decanedioic acid, HOOC (CH2)iqCOOH, to produce to silk-like fibre Quiana (Du Pont). 

Cyclic amines such as piperidine and its derivatives show substantial differences in the properties of the axial C-2 and C-6 versus the equatorial C-2 and C-6 C—H bonds. 

Delphonine shows an unusually high basic dissociation constant, and that of aconine is only a little less. In the case of tertiary vinyl cyclic amines, which prove to be unexpectedly strong bases, Adams and Mahan suggested that they exist in solution as equilibrium mixtures consisting of the tertiary unsaturated base and a quaternary arrangement in which the double bond has moved to the nitrogen, which may be represented thus —. . . +. . . +... 

Electrochemical fluonnation ot N,N dialkylammo-substituted carboxylic acids as their methyl esters produces the analogous perfluonnated tertiary amine carboxylic acid derivatives in 18-30% yields as well as cyclic amine ethers [JOO]... 

The secondary amines used in the preparation of enamines have been primarily simple dialkylamines or cyclic amines of five- or higher-membered rings. Azetidine (4) yields a stable enamine with cyclopentanone (28). No simple enamines formed by condensation of ethylenimine (5) or a substituted ethylenimine with an aldehyde or ketone have been reported. 

That an aminal is a necessary intermediate was first questioned by Herr and Heyl (2). They found that by using a slight excess of amine the yield of the enamine from two of the steroidal aldehydes studied was 84%. Also, the -fluorocnamines discussed earlier are formed in 60-90% yield from equimolar amounts of the 8-fluoroaldehyde and secondary cyclic amine (27). However, neither of these studies was specifically designed to show whether or not aminals were intermediates. 

Experiments designed to clarify the situation were carried out by Wittig and Mayer (40). It was shown that changing the molar ratio of amine (diethylamine, di- -butylamine, or diisobutylamine) to -butyraldehyde from 1 1 to 2 1 did not affect the yield of enamine (53- 64%, based on the aldehyde). Contrariwise, changing the ratio of amine (morpholine, piperidine, or pyrrolidine) to n-butyraldehyde from 1 1 to 2 1 boosted the yields from 52-57 % to 80-85 %. The authors interpret these data as indicating that the cyclic amines form aminals with n-butyraldehyde, while the open-chain do not. Infrared evidence is stated as having shown that the aminal originates not from attack of excess amine on the enamine, which is stable under the conditions of the reaction, but from the N-hemiacetal (17). 

Formation and transformations of cyclic amines and lactams 98JCS(P1)2959, 99JCS(P1)2209. 

Eullerene-based donor-acceptor complexes and ion-radical salts with tetrathia-fulvalenes, metalloporphyrins, and cyclic amines as donors 99UK23. 

Selective hydrolysis of the 3-carboxylate with 6N-HCl/AcOH was unsuccessful and instead the 4-carboxylate hydrolyzed to the corresponding acid, however, heating of 432 at 50 °C caused its hydrolysis and decarboxylation in one step. Subsequent reaction with either MnO or DDQ gave 433. The fluorine atom at 8-position could be replaced by cyclic amines to give the 8-pyrrolyl or 8-[l-methyl-4-piperazinyl] derivatives 436 which upon hydrolysis using either acidic or basic conditions afforded the... 

Reductive cyclization of 4-piperidinecarboxamide 562 afforded 563 which could be alternatively obtained by condensation of 564 with the respective cyclic amine. Compound 563 showed inhibition of writhing in mice (96EP700913). Similarly, 565 gave 566 (76JMC1111) (Scheme 94). 

Reaction of 9,10-difluoro-7-oxo-2,3-dihydro-7//-pyrido[l, 2,3- e]-1,4-ben-zothiazine-6-carboxylic acid and its ethyl ester with B(OH)3 in AC2O in the presence of ZnCl2 afforded 6-[(diacetoxyboryl)oxycarbonyl] derivative 323 (R = OAc)], which was reacted with primary and cyclic amines to give 10-amino-9-fluoro-7-carboxylic acid derivatives 324 (97MI41, 98MI30). 6-[(Difluoroboryl)oxycarbonyl derivative 323 (R = F) was obtained from ethyl 9,10-difluoro-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazine-6-carboxylate with BF3-THF complex. Reaction of 323 (R = F) and 1-methylpiperazine in DMF at 50-60 °C and subsequent acidic hydrolysis afforded 7 (97MI1). 

Ring-alkohol, m. cyclic alcohol, -amin, n. cyclic amine. 

Quaternary ammonium salts. Salts of alkyl amines. Alkyl chain substituted cyclic amines Acidic pH range Alkaline pH range... 

For aliphatic monoamine [43], it is shown that secondary amines R2NH always possess a higher promoting effect for the polymerization of AAM and even the primary amine PA will enhance the polymerization with Rr = 1.47 and Ea = 36.4 kJ/mol, while the tertiary aliphatic amine TPA will not provide the polymerization due to some steric hindrance (Table 6). All of the data of cyclic amines listed in Table 7 are effective, i.e., NMMP with Rr = 1.81 and Ea = 29.9 kJ/mol showing the absence of steric hindrance. 

Table 7 Effects of Aliphatic Cyclic Amines on Polymerization...

The reaction is effective with both acyclic and cyclic amides., or lactams, and is a good method for preparing cyclic amines. 

The net effect of the Stork reaction is the Michael addition of a ketone to an cn/3-unsaturated carbonyl compound. For example, cyclohexanone reacts with the. cyclic amine pyrrolidine to yield an enamine further reaction with an enone such as 3-buten-2-one yields a Michael adduct and aqueous hydrolysis completes the sequence to provide a 1,5-diketone (Figure 23.8). 

Amines occur widely in all living organisms. Trimethylamine, for instance, occurs in animal tissues and is partially responsible for the distinctive odor of fish, nicotine is found in tobacco, and cocaine is a stimulant found in the South American coca bush. In addition, amino acids are the buildingblocks from which all proteins are made, and cyclic amine bases are constituents of nucleic acids. 

Other Enolate Additions Leading to Cyclic Amines... 

Mass 28 in cyclic amines is CH2N. Mass 30 is fairly intense in nonsubstituted cyclic amines. 

Molecular ions as well as [M - H]+ ions are observed for cyclic amines. 

Cyclic amines unsubstituted on the nitrogen Primary aminest... 

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