Synthesis of Trialkylamines with Extreme Steric Hindrance and Their Decay by a Hofmann-like Elimination Reaction.

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.

The Simplest, Isolable, Alkynyl Isocyanate HC≡CNCO: Synthesis and Characterization.

Alkynyl isocyanates have been postulated as highly reactive intermediates in synthetic chemistry. Herein, the parent molecule HC≡CNCO is isolated for the first time. In sharp contrast to the previously reported short lifetime (ca. 15 s) at room temperature, we found that HC≡CNCO has a lifetime of 55 h in the gas phase (2 mbar, 300 K) with a melting point of -79.5 °C and vaporization enthalpy (ΔHvap ) of 23.1(1) kJ mol-1 . Apart from the IR (gas, solid, and matrix), 1 H and 13 C NMR, and UV/Vis spectroscopic characterization, its photoisomerization with a acylnitrene HC≡CC(O)N and cyanoketene NCC(H)CO has been observed.

Tricyanomethane and Its Ketenimine Tautomer: Generation from Different Precursors and Analysis in Solution, Argon Matrix, and as a Single Crystal.

Solutions of azidomethylidenemalononitrile were photolyzed at low temperatures to produce the corresponding 2H-azirine and tricyanomethane, which were analyzed by low-temperature NMR spectroscopy. The latter product was also observed after short thermolysis of the azide precursor in solution whereas irradiation of the azide isolated in an argon matrix did not lead to tricyanomethane, but to unequivocal detection of the tautomeric ketenimine by IR spectroscopy for the first time. When the long-known "aquoethereal" greenish phase generated from potassium tricyanomethanide, dilute sulfuric acid, and diethyl ether was rapidly evaporated and sublimed, a mixture of hydronium tricyanomethanide and tricyanomethane was formed instead of the previously claimed ketenimine tautomer. Under special conditions of sublimation, single crystals of tricyanomethane could be isolated, which enabled the analysis of the molecular structure by X-ray diffraction.

Synthesis, Characterization and Reactions of (Azidoethynyl)trimethylsilane.

Synthesis of azido(trimethylsilyl)acetylene (6) was performed by treating the iodonium salt 5 with highly soluble hexadecyltributylphosphonium azide (QN3) at -40 °C. Although this product is very unstable, it can nevertheless be trapped by the click reaction with cyclooctyne to give the corresponding 1,2,3-triazole, and also directly characterized by ¹H- and (13)C-NMR data as well as IR-spectra, which were measured in solution at low temperature and in the gas phase. The thermal or photochemical decay of azide 6 leads to cyano(trimethylsilyl)carbene. This is demonstrated not only by quantum chemical calculations, but also by the trapping reactions with the help of isobutene.

Rearrangement Reactions of Tritylcarbenes: Surprising Ring Expansion and Computational Investigation.

As a rule, acetylides and sulfonyl azides do not undergo electrophilic azide transfer because 1,2,3-triazoles are usually formed. We show now that treatment of tritylethyne with butyllithium followed by exposure to 2,4,6-triisopropylbenzenesulfonyl azide leads to products that are easily explained through the generation of short-lived tritylethynyl azide and its secondary product cyanotritylcarbene. Furthermore, it is demonstrated that tritylcarbenes generally do not produce triphenylethenes exclusively, as was stated in the literature. Instead, these carbenes always yielded also (diphenylmethylidene)cycloheptatrienes (heptafulvenes) as side products. This result is supported by static DFT, coupled cluster, and ab initio molecular dynamics calculations. From these investigations, the fused bicyclobutane intermediate was found to be essential for heptafulvene formation. Although the bicyclobutane is also capable of rearranging to the triphenylethene product, only the heptafulvene pathway is reasonable from the energetics. The ethene is formed straight from cyanotritylcarbene.

Elusive ethynyl azides: trapping by 1,3-dipolar cycloaddition and decomposition to cyanocarbenes.

Although they decompose rapidly to produce cyanocarbenes, ethynyl azides were generated from (chloroethynyl)arenes and trapped for the first time by 1,3-dipolar cycloaddition at cyclooctyne.

Synthesis, configuration, and (15)n NMR spectra of iminoaziridines. Synthons equivalent to three components of the Ugi reaction.

Monocyclic iminoaziridines and exo-endo diastereomers of spirocyclic iminoaziridines that are derived from norbornane are prepared in batches of up to 10 g to foster applications as building blocks in syntheses. N,N'-Disubstituted alpha-haloamidines, which are readily available in two steps from N-substituted alpha-halocarboxamides, are 1,3-dehydrohalogenated by strong bases such as alkali-metal hydrides or tert-butoxides to afford distillable oils or low-melting solids, which consist of slowly interconverting E-Z diastereomers of the title compounds. The scope and limitations are outlined for this reaction. The configurations E and Z that were assigned on the basis of homoallylic 1H-1H coupling and asymmetric solvent-induced shifts required that, in 13C NMR spectra, the observed gamma-effects of substitutents at the imino nitrogens were deshielding, contrary to the well-known shielding gamma-effects in all other types of C=N compounds. However, an NOE NMR study demonstrated unequivocally that the previous assignments are correct and hence the observed gamma-effects actually deshielding. The ranges of 15N NMR chemical shifts span more than 60 ppm. Neither the beta- nor the gamma-effects of substituents on both types of nitrogen follow a uniform increment pattern.

Intralesional therapy of metastatic spreading melanoma with beta-interferon.

A 74-year-old female patient developed multiple local metastases after excision of a nodular melanoma of the left cheek. There was no regression after treatment with dacarbazine (DTIC) and radiotherapy. After treatment with intralesional interferon-beta, the metastases regressed completely. The dosage was 5 million IU interferon-beta (Fiblaferon) three times weekly with courses of two and four weeks, separated by a month. Except for local swelling and inflammation, no side effects occurred. Five years after completing therapy, the patient is still tumor-free.

[Acquired reactive perforating collagenosis after curettage of seborrheic keratoses]. / Erworbene reaktiv perforierende Dermatose nach Kurettage seborrhoischer Keratosen.

Acquired reactive perforating collagenosis (ARPC) developed in an 81-year-old woman two weeks after curettage of seborrheic keratoses. Treatment with allopurinol and antipruritic ointment was given. After four months, there was complete re-epithelialization, leaving atrophic scars.

[Lichen sclerosus and squamous cell carcinoma of the vulva]. / Lichen sclerosus und Vulvakarzinom.

Genital lichen sclerosus in women is a clinically and histologically well defined disease. In addition to the classical atrophic form, there is a hypertrophic variant, which is characterised histologically by squamous cell hyperplasia. The aetiology is unknown but an autoimmune pathogenesis seems most likely. Infectious or hormonal influences do not play a major role. We describe a squamous cell carcinoma of the vulva with a co-existing lichen sclerosus. This case raises again the question of a precancerous potential of lichen sclerosus. In the dermatological literature, only a few cases with association of lichen sclerosus and squamous cell carcinoma are known. This is in contrast to gynaecological literature, where a high number of squamous cell carcinomas has been described. Gynaecologists search for the histological findings of lichen sclerosus adjacent to squamous cell carcinoma. Such an attempt is not valid without the clinical signs of lichen sclerosus, so that indeed classical lichen sclerosus does not seem to be a precancerous lesion. On the other hand, the hypertrophic form of lichen sclerosus seems to be associated with squamous cell carcinoma in about 3-5% of case.