The synthesis of 4-dialkylaminopyridines can be accomplished in two steps starting from pyridine. Compared to pyridine, these derivatives are approximately 104 times more active when used as acylation catalysts. Dialkylaminopyridines are being used with ever-increasing frequency for acylation reactions which proceed either incompletely or not at all in pyridine. This article reviews the various possible applications of 4-dialkylaminopyridines in terpene, steroid, carbohydrate and nucleoside chemistry as well as in the transformation of amino acids into α-acyl aminoketones and polymerization of isocyanates. In addition, N-substituted 4-dialkylaminopyridinium salts can be used for the transfer of sensitive groups to nucleophiles in aqueous medium. The exceptional catalytic effect of these derivatives, even in non-polar solvents, is due, in part, to the formation of high concentrations of N-acylpyridinium salts which are present in solution as loosely-bound, highly reactive ion pairs.

4-Dialkylaminopyridines as Highly Active Acylation Catalysts. [New synthetic method (25)]

A Cook's tour is presented of the organosulfur chemistry of the genus Allium, as represented, inter alia, by garlic (Allium sativum L.) and onion (Allium cepa L.). We report on the biosynthesis of the S-alk(en)yl-L-cysteine S-oxides (aroma and flavor precursors) in intact plants and on how upon cutting or crushing the plants these precursors are cleaved by allinase enzymes, giving sulfenic acids—highly reactive organosulfur intermediates. In garlic, 2-propenesulfenic acid gives allicin, a thiosulfinate with antibiotic properties, while in onion 1-propenesulfenic acid rearranges to the sulfine (Z)-propanethial S-oxide, the lachrymatory factor (LF) of onion. Highlights of onion chemistry include the assignment of stereochemistry to the LF and determination of the mechanism of its dimerization; the isolation, characterization, and synthesis of thiosulfinates which most closely duplicate the taste and aroma of the freshly cut bulb, and additional unusual compounds such as zwiebelanes (dithiabicyclo[2.1.1]hexanes), a bis-sulfine (a 1,4-butanedithial S,S′-dioxide), antithrombotic and antiasthmatic cepaenes (α-sulfinyl disulfides), and vic-disulfoxides. Especially noteworthy in the chemistry of garlic are the discovery of ajoene, a potent antithrombotic agent from garlic, and the elucidation of the unique sequence of reactions that occur when diallyl disulfide, which is present in steam-distilled garlic oil, is heated. Reaction mechanisms under discussion include [3, 3]- and [2, 3]-sigma-tropic rearrangements involving sulfur (e.g. sulfoxide-accelerated thio- and dithio-Claisen rearrangements) and cycloadditions involving thiocarbonyl systems. In view of the culinary importance of alliaceous plants as well as the unique history of their use in folk medicine, this survey concludes with a discussion of the physiological activity of the components of these plants: cancer prevention, antimicrobial activity, insect and animal attractive/repulsive activity, olfactory–gustatory–lachrymatory properties, effect on lipid metabolism, platelet aggregation inhibitory activity and properties associated with ajoene. And naturally, comments about onion and garlic induced bad breath and heartburn may not be overlooked.

The Organosulfur Chemistry of the Genus Allium – Implications for the Organic Chemistry of Sulfur

Although the concept of using pharmacologically active macromolecular compounds as drugs is still regarded with much skepticism for both theoretical and practical reasons, interest in this field has grown in recent years because of the opportunity to take advantage of the specific properties of polymeric materials. For low molecular weight drugs, changes in structure often lead to a loss of specific activity. On the other hand, the properties of macromolecular drugs depend on the structure of the polymer used and this can be varied over a wide range by the incorporation of comonomer units, by the application of polymer-analogous reactions, or by related structural changes. A new model is presented for pharmacologically active polymers which incorporates the possibility for continuous variation in (a) solubility and toxicity, (b) fixation and removal of active material, and (c) body distribution. Using the new model as a guide, examples of the synthesis and study of the biological activity of various macromolecular drugs are presented in order to emphasize the importance of this cooperative effort between polymer research and therapeutic problems.

Structure and properties of pharmacologically active polymers

4‐Dialkylaminopyridine als hochwirksame Acylierungskatalysatoren

Chlorophyll‐ und Häminderivate in organischen Mineralstoffen

Thermodynamic Data, Heterocyclic Seven-Membered Ring Compounds On heating in carbon tetrachloride or nitromethane the 5-methoxy-1-benzothiepines 1-4 isomerize to the corresponding thionaphtholes 5-8, whereas in cyclohexane from 1-4 the usual desulfuration products C arise. Kinetic and thermodynamic data have been estimated for the reactions 3 → 7 and 4 → 8. If the thermal rearrangement of 3 resp. 4 takes place in presence of cyclohexene sulphide, one gets the desulfuration products C also in carbon tetrachloride or nitromethane as solvent together with the equimolar amount of cyclohexene. This behaviour leads to the assumption of a S2-spezies as the primary elimination product of sulphur from the episulphide intermediate A.

Heterocyclische Siebenring-Verbindungen, XXXV / Heterocyclic Seven-Membered Ring Compounds, XXXV

Ringverengung von 1-Thio-chromanen zu Benzo[b]thiophenen

Die thermische Umlagerung des 1-Benzoxepins 1 fuhrt bei Temperaturen um 150°C zu einem Gemisch der isomeren Naphthole 2 und 3, deren Entstehung spektroskopisch, durch Uberfuhrung in die Methylather 4 und 5 sowie durch gezielte Synthese von 5 bewiesen wird. Mogliche Mechanismen der Isomerenbildung werden diskutiert. Acetoxynaphthole wie 2 und 3 erweisen sich ab ca. 150°C selbst als instabil. Andere 3-Acetoxy-1-benzoxepine verhalten sich wie 1.



Heterocyclic Seven-membered Ring Compounds, XIII. A Side-reaction competing with α-Naphthol Formation from 3-Acetoxy-1-benzoxepines



Thermally induced rearrangement of 1-benzoxepine 1 at about 150°C yields a mixture of the naphthol isomers 2 and 3, the formation of which is proved spectroscopically as well as by transformation into the methyl ethers 4 and 5, resp., and by independent synthesis of compound 5, Possible reaction-pathways to 2 and 3 are discussed. Acetoxynaphthols such as 2 or 3 are unstable at temperatures higher than 150°C. Other 3-acetoxy-substituted 1-benzoxepines are found to behave as reported for compound 1.

Heterocyclische Siebenring-Verbindungen, XIII. Über eine Konkurrenzreaktion zur α-Naphthol-Bildung aus 3-Acetoxy-1-benzoxepinen

Abstract Alkylation of 1,5-benzothiazepin-4(5H)-one (1) with dimethyl sulfate and base yields the N-methyl compound 2 whereas with trimethyloxonium fluoroborate the lactimether 3, a simple derivative of the unknown, 1,4-thiazepine is obtained. Compound 3 eliminates sulfur on heating in toluene, yielding 2-methoxy-quinoline. Oxidation of 3 with peracid produces the stable 1,1- dioxide (4).

Heterocyclische Siebenring-Verbindungen, XXX Synthese und Eigenschaften von 4-Methoxy-1,5-benzothiazepin, einem einfachen Vertreter des 1,4-Thiazepin-Ringsystems/ Heterocyclic Seven-Membered Ring Compounds, XXX Synthesis and Properties of 4-Methoxy-1,5-benzothiazepine, a Simple Derivative of the 1,4-Thiazepine Ring System

Hans Hofmann

Papers

Heterocyclische Siebenring-Verbindungen, XXXV / Heterocyclic Seven-Membered Ring Compounds, XXXV

Ringverengung von 1-Thio-chromanen zu Benzo[b]thiophenen

Heterocyclische Siebenring-Verbindungen, XIII. Über eine Konkurrenzreaktion zur α-Naphthol-Bildung aus 3-Acetoxy-1-benzoxepinen

Heterocyclische Siebenring‐Verbindungen, XXV Synthese und thermische Umlagerung von substituierten 1‐Methyl‐4‐phenyl‐1‐benzothiepinium‐Salzen