Related info: Pseudonitrosite Synthesis, as Performed by Pugsley

Introduction

The hitherto pretty unknown pseudonitrosites are nitrogenous compounds which are formed by the action of N₂O₃ (an equimolar mixture of NO and NO₂) upon etheral solutions of some unsaturated compounds, for example propenylbenzenes and styrenes. They were popular in the late 1800s and early 1900s, but has since then been forgotten(?). After around WWII, there is not a single mention of them in the literature, not even in such a reference work on the subject as Nitroalkenes - Conjugated Nitro Compounds¹.

The pseudonitrosites were discovered by Toennies around 1880, when he made the pseudonitrosite of anethol, but he failed to recognize the constitution of the compound, and mistakenly assigned it the structure of a vicinal ketoxime/nitrite. In the early 1890s, the Italian chemist Angelo Angeli experimented with different allyl- and propenylbenzenes, and again encountered the pseudonitrosites, but he couldn't either determine their exact structure, and with the methods used in analytical chemistry back then, this is understandable. In the early 1900s, the puzzle was solved by studies on styrene pseudonitrosite, and around this time Wallach and Wieland published reviews of pseudonitrosite chemistry^2-3. Very little about pseudonitrosites can be found in Chemical Abstracts, so most pointers to earlier work must be retrieved from the references cited in those articles.

In the 1930's, Victor Bruckner began to explore the possibility of using pseudonitrosites as an intermediate in the synthesis of substituted 1-phenyl-2-amino-propanols, and in his articles he also included improved syntheses of several pseudonitrosites from propenylbenzenes, as well as studies on the pseudonitrosites themselves. One of the most useful reactions he investigated was the basic hydrolysis of propenylbenzene pseudonitrosites, yielding the corresponding beta-nitro derivatives of the propenylbenzenes. This route offered several advantages over the known nitration of alkenes with tetranitromethane, which is expensive, toxic and explosive. In his papers on pseudonitrosites, Bruckner described several experiments with asarone⁴, methylisoeugenol and isosafrole⁵, isoeugenol⁶ and anethole⁷. In the experimental part below, some freely translated parts of his work is included.

Theory

Several methods for the synthesis of pseudonitrosites have been used, such as bubbling N₂O₃ through a solution of the propenylbenzenes in ether, slow addition of a NaNO₂ solution to a solution of the propenylbenzene in glacial acetic acid (Toennies' method), as well as dripping a dilute solution of sulfuric acid into a two-phase solution of NaNO₂ in water and a propenylbenzene in ether (Bruckner's method).

The action of a strong acid (such as sulfuric acid) on sodium nitrite gives the sodium salt of the strong acid, as well as free nitrous acid (HNO₂), which in turn breaks down to an equimolar mixture of NO and NO₂ gas (see Fig. 2). This gas mixture is in equilibrium with dinitrogen trioxide: N₂O₃ ←→ NO + NO₂

At 25°C and normal pressure, only about 10% of the gas is in the form of N₂O₃, and the equilibrium mixture behaves just like as if it was a mixture of NO and NO₂. But, for the sake of simplicity, the equilibrium mixture is commonly called N₂O₃, or dinitrogen trioxide.

N₂O₃ can also be formed by the action of nitric acid (which in turn can be made by dissolving NaNO₃ or KNO₃ in conc H₂SO₄) on certain metals, for example iron (see Fig. 3). The more finely divided the metal, the faster generation of gas. But there is a downside to this method. In the beginning the nitric acid is concentrated, but as N₂O₃ is evolved, the solution becomes more and more dilute. There is a problem associated with this, the ratio of NO to NO₂ isn't constant if the concentration of the acid changes. Concentrated acid gives excess NO₂, and a dilute acid solution gives excess NO. To get maximum yields out of the treated propenylbenzene, the proportions between NO and NO₂ should always be as close to 1:1 as possible, and only the sodium nitrite method will constantly produce a gas mixture with just those proportions. Producing dinitrogen trioxide with the nitrate method is therefore discouraged. This method does not work at all with asarone (only with other propenylbenzenes, such as isosafrole or anethole) according to Bruckner⁴.

The pseudonitrosites always dimerizes to the bis-pseudonitrosites, all of which are practically insoluble in water, alcohols and most common organic solvents, with the exception of warm chloroform or ethyl acetate, in which a blue-green solution is produced, consisting of the dissociated pseudonitrosite monomer. During the treatment of a propenylbenzene with N₂O₃, the intensely colored free monomer can be observed for a while before it dimerizes to its crystalline form. The colors of the crystalline pseudonitrosites varies, from the snow-white isosafrole or anethole derivatives to the canary-yellow one obtained from asarone. Upon storage, pseudonitrosites soon decompose with discoloration, releasing nitrogen oxides and hydrogen cyanide. At around 40°C decomposition takes place in less than one day.

Treatment of the pseudonitrosite dimer with four moles of an inorganic base (such as KOH in alcohol), produces two moles of potassium hyponitrite (K₂N₂O₂) and two moles of the water-soluble potassium salt of the corresponding nitroalkene. Acidification of the potassium salt solution with dilute acid precipitates the water-insoluble phenyl-2-nitropropene as fine crystals, and the liberated hyponitrous acid breaks down into water and nitrous oxide (N₂O), which can be observed as fine bubbles that is being evolved during this step.

The reaction of a pseudonitrosite with acetic anhydride produces the alpha-acetoxy derivative with release of N₂O, and after reduction of the nitro group this could be hydrolyzed to ring substituted phenylpropanolamine derivatives. Basic hydrolysis of the alpha-acetoxy derivative also produces the phenyl-2-nitropropene. Reaction of pseudonitrosites with primary amines yields secondary alpha-amino derivatives.