Ten different processes (Methods A-J) were tested to prepare tertiary amines bearing bulky alkyl groups. In particular, S1 alkylation of secondary amines with the help of 1-adamantyl triflate (Method D) and reaction of N-chlorodialkylamines with organometallic reagents (Method H), but also attack of the latter reagents at iminium salts, which were generated in situ by N-alkylation of imines (Method J), led to trialkylamines with unprecedented steric congestion. These products showed a restriction of the rotation about the C-N bond. Consequently, equilibration of rotamers was slow on the NMR time scale resulting in distinguishable sets of NMR data at room temperature. Furthermore, tertiary amines with bulky alkyl substituents underwent Hofmann-like elimination when heating in toluene to form an olefin and a secondary amine. Since the tendency to take part in this decay reaction correlated with the degree of steric hindrance around the nitrogen atom, Hofmann elimination at ambient temperature, which made the isolation of the tertiary amine difficult, was observed in special cases.
A number of amines with three bulky alkyl groups at the nitrogen, which surpass the steric crowding of triisopropylamine considerably, were prepared by using different synthetic methods. It turned out that treatment of N-chlorodialkylamines with organometallic compounds, for example, Grignard reagents, in the presence of a major excess of tetramethylenediamine offered the most effective access to the target compounds. The limits of this method were also tested. The trialkylamines underwent a dealkylation reaction, depending on the degree of steric stress, even at ambient temperature. Because olefins were formed in this transformation, it showed some similarity with the Hofmann elimination. However, the thermal decay of sterically overcrowded tertiary amines was not promoted by bases. Instead, this reaction was strongly accelerated by protic conditions and even by trace amounts of water. Reaction mechanisms, which were analyzed with the help of quantum chemical calculations, are suggested to explain the experimental results.
Several amines with three bulky alkyl groups at the nitrogen atom, which exceed the steric crowding of triisopropylamine significantly, were synthesized, mainly by treating N‐chlorodialkylamines with Grignard reagents. In six cases, namely tert‐butyldiisopropylamine, 1‐adamantyl‐tert‐butylisopropylamine, di‐1‐adamantylamines with an additional N‐cyclohexyl or N‐exo‐2‐norbonyl substituent, as well as 2,2,6,6‐tetramethylpiperidine derivatives with N‐cyclohexyl or N‐neopentyl groups, appropriate single crystals were generated that enabled X‐ray diffraction studies and analysis of the molecular structures. The four noncyclic amines adopt triskele‐like conformations, and the sum of the three C−N−C angles is always in the range of 351.1° to 352.4°. Consequently, these amines proved to be structurally significantly flatter than trialkylamines without steric congestion, which is also signalized by the smaller heights of the NC3 pyramids (0.241–0.259 Å). There is no clear correlation between the heights of these pyramids and the degree of the steric crowding in the new amines, presumably because steric repulsion is partly compensated by dispersion interaction. In the cases of the two heterocyclic amines, the steric stress is smaller, and the molecular structures include quite different conformations. Quantum chemical calculations led to precise gas‐phase structures of the sterically overcrowded trialkylamines exhibiting heights of the NC3 pyramids and preferred molecular conformers which are similar to those resulting from the X‐ray studies.
The reaction of isocyanates with substituted imidazolines and the thermally induced cleavage of the resulting adducts are presented. For this purpose, reactions of various isocyanates [ethyl isocyanate, p-methylphenyl isocyanate, phenyl isocyanate, p-(trifluoromethyl)phenyl isocyanate] with 1-alkylimidazoline derivatives have been studied as a function of the substituent at the 2-position of the imidazoline ring. Three equivalents of isocyanate react with one equivalent of 1-ethylimidazoline to give a stoichiometric well-defined adduct. However, 1-ethyl-2-isopropylimidazoline reacts with isocyanates at 0 °C in another way, with formation of 2:1 adducts which belong to the family of 1,3-diphenyltetrahydroimidazo[1,2-a][1,3,5]triazine-2,4(1H,3H)-diones. The reaction of 1-ethyl-2-methylimidazoline with aromatic isocyanates at 0 °C also leads to 2:1 adducts, in this case of a malonamide type, which can react at 60 °C with an additional isocyanate equivalent to give the known pyrimidinediones. Thermal analysis (TG-MS/DSC) and trapping reactions with nucleophilic reagents, such as diphenylamine, show the release of isocyanate during the thermally induced cleavage reaction. Thus, blocked isocyanates are available by the reaction of isocyanates with 1-ethylimidazoline or 1-ethyl-2-isopropylimidazoline.
Even record‐breaking steric stress cannot enforce complete planarization of the nitrogen atom in trialkylamines. This is demonstrated for several examples with the aid of single‐crystal X‐ray diffraction studies. Moreover, quantum chemical calculations generate the precise gas‐phase structures of the sterically overcrowded tertiary amines showing heights of the NC3 pyramids and preferred molecular conformers, which are similar to those resulting from the X‐ray analysis. More information can be found in the Full Paper by K. Banert, M. Wörle, A. D. Boese, et al. on page 3700.
Epoxidation of olefinic heterocyclic amines and subsequent acid-catalyzed hydrolysis or alternatively the direct dihydroxylation with the help of osmium tetroxide led to diols, which underwent ring cleavage in the presence of lead tetraacetate to give 3-isopropyl-2,2,4,4-tetramethyl-3-azahexanedial and 3-tert-butyl-2,2,4,4-tetramethyl-3-azapentanedial. Whereas the former dialdehyde is a highly unstable model compound because of a rapid intramolecular aldol reaction, the latter product proves to be isolable at room temperature. Furthermore, this compound is the first open-chain tri-tert-alkylamine establishing in a new record of steric crowding in tertiary amines. Strong tendencies to a Hofmann-like elimination reaction or to ring-closing reactions were observed when the aldehyde units of 3-tert-butyl-2,2,4,4-tetramethyl-3-azapentanedial were transformed into other functionalities, since both types of reactions led to a significantly decrease of the steric stress.
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