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

Durch Umlagerung von 3.α-Epoxy-3-benzyl-chromanonen-(4), 3.α-Epoxy-3-benzyl-1-thiochromanonen-(4) und von 3.α-Epoxy-3-benzyl-1-thio-chromanon-(4)-1.1-dioxiden (1–5, 1316) wurden 4-Aryl-2.3.4.5-tetrahydro-1-benzoxepin-dione-(3.5) und die analogen Verbindungen mit Sulfid- bzw. Sulfonfunktion erhalten (18–22, 23–26). Daraus haben sich Mono- (27–30) und Di-enolacetate (34–39) darstellen lassen. Die letzteren sind Derivate des 1-Benzoxepins, 1-Benzothiepins und 1-Benzothiepin-1.1-dioxids.

Synthese von Derivaten des 1‐Benzoxepins, 1‐Benzothiepins und 1‐Benzothiepin‐1.1‐dioxids

3-Benzyliden-chromanone-(4) werden mit natronalkalischer, methanolischer Wasserstoffperoxydlosung glatt zu 3.α-Oxido-3-benzyl-chromanonen-(4) epoxydiert.

Chromane, XIII. Die Epoxydation von 3‐Benzyliden‐chromanonen‐(4) zu 3.α‐Oxide‐3‐benzyl‐chromanonen‐(4)

Aus 3.5-Diacetoxy-4-phenyl-1-benzoxepin (1) entsteht beim Erhitzen in Xylol 2.4-Diacetoxy-3-phenyl-naphthol-(1) (6); mit Natriumacetat/Acetanhydrid erhalt man das entsprechende Acetat. Aus dem gleichartigen 1-Benzothiepin 2 bekommt man beim Erhitzen in Xylol und auch mit Pyridin/Acetanhydrid unter Eliminierung von Schwefel 1.3-Diacetoxy-2-phenylnaphthalin (5); mit Natriumacetat/Acetanhydrid entsteht dagegen der Thioessigsaure-S-[2.4-diacetoxy-3-phenyl-naphthyl-(1)-ester] (7). Das analoge 1-Benzothiepin-1.1-dioxid (9) liefert mit Natriumacetat/Acetanhydrid in einer andersartig verlaufenden Umlagerung das Cyclobuta[b]-1-benzothiophen-3.3-dioxid 10, dessen Struktur durch Abbau gesichert wird.

Umlagerungsreaktionen von Derivaten des 1‐Benzoxepins, 1‐Benzothiepins und des 1‐Benzothiepin‐1.1‐dioxids

Aus 7.8-Dibenzyloxy-3-[3.4-dibenzyloxy-benzyliden]-chromanon-(4) bildet sich mit Hydroperoxid in alkalischer Losung das Epoxyketon, welches mit NaBH4 und LiAlH4 stufenweise zu einem Gemisch isomerer, racem. 3.4-Dihydroxy-7.8-dibenzyloxy-3-[3.4-dibenzyloxy-benzyl]-chromane reduziert wird. Aus diesem Gemisch entsteht beim Ringschlus in Eisessig mit Perchlorsaure (±)-Hamatoxylin-tetrabenzylather, der bei katalytischer Hydrierung zu (±)-Hamatoxylin entbenzyliert wird.

Chromane, XVII: Die Synthese von (±)-Hämatoxylin

Die 5-Methoxy-2,3-dihydro-Vorstufe 2 wird in die 4-Phenyl-1-benzothiepine 7 und 8 ubergefuhrt; aus der 2,5-Dihydro-Vorstufe 12 werden die 4-Phenyl-1-benzothiepine 13 und 14 dargestellt Das 1-Benzothiepin 17 wird direkt aus dem Siebenring-Diketon 1 erhalten Das 3-cyan-substituierte 1-Benzothiepin 22 erhalt man aus der 2,5-Dihydro-Vorstufe 21 Es werden einige Ringverengungsbzw Ringspaltungsreaktionen des heterocyclischen Siebenring-Systems beschrieben



Heterocyclic Seven-membered Ring Compounds, XVI Synthesis of 3,5-Substituted 4-Phenyl-1-benzothiepins



4-Phenyl-1-benzothiepins 7 and 8 are synthesized starting from their 5-methoxy-2,3-dihydro-precursor 2; using the 2,5-dihydro-intermediate 12 yields the 4-phenyl-1-benzothiepins 13 and 14 The 1-benzothiepin 17 can be obtained from the diketone 1 directly The 3-cyano-substituted compound 22 is prepared from its 2,5-dihydro-precursor 21 Some ring-contraction and ring-cleavage reactions of the heterocyclic seven-membered ring-system are described

Hans Hofmann

Papers

Synthese von Derivaten des 1‐Benzoxepins, 1‐Benzothiepins und 1‐Benzothiepin‐1.1‐dioxids

Chromane, XIII. Die Epoxydation von 3‐Benzyliden‐chromanonen‐(4) zu 3.α‐Oxide‐3‐benzyl‐chromanonen‐(4)

Umlagerungsreaktionen von Derivaten des 1‐Benzoxepins, 1‐Benzothiepins und des 1‐Benzothiepin‐1.1‐dioxids

Chromane, XVII: Die Synthese von (±)-Hämatoxylin

Heterocyclische Siebenring-Verbindungen, XVI. Synthese gezielt 3,5-substituierter 4-Phenyl-1-benzothiepine