Why use freshly distilled benzaldehyde

Instead of running this reaction at elevated temperatures for a few hours, we will allow the reaction to proceed closer to room temperature for 24 hours or more.

Benzaldehyde is easily oxidized to benzoic acid which can impede the desired reaction so freshly distilled benzaldehyde is used. The concentration of reactants and temperatures of solutions are critical to obtaining a good yield so procedures must be followed carefully. Too much water will force benzaldehyde out of solution preventing an efficient reaction. Too little water prevents the thiamine hydrochloride from dissolving.

Some of the base reacts with the thiamine hydrochloride to produce thiamine which is the active catalyst. Procedure : Place 1. In a 50 mL Erlenmeyer flask dissolve 0. Add 7. While keeping both flasks in the ice bath, add the 1. Remove the 50 mL flask from the ice bath, add 5. Seal the flask with Parafilm and place it in your drawer until the next lab period.

You can use hot water from the faucets at the front of the lab. The mixture should become homogeneous in the water bath but it may not stay homogeneous once it cools. You should not have to filter the hot solution.

Obtain the mp of the recrystallized benzoin lit mp listed as and o C for d, l -benzoin, most students will see a mp of o C. When you are satisfied that you have the product you want, you may dispose of the first filtrate by neutralizing with dilute HCl, then flushing the aqueous layer down the drain with plenty of water.

The second filtrate from recrystallization can be flushed down the drain with water. Work in a hood! Into a mL Erlenmeyer flask, place 2. Heat the mixture on a steam bath with occasional slow swirling for 30 minutes or until the brown-red nitric oxide gases are no longer evolved.

The fumes are toxic and noxious so be certain that the fume hood safety shield is pulled down. Carefully cool the flask and contents using tap water keep the flask covered with a plastic seal or a cork , then pour into 35 mL of cool water and swirl to coagulate the precipitated product.

Collect the yellow solid using suction filtration and wash twice with 5 mL of cool water to remove some of the nitric acid present. Press the crystals to remove more water by placing another piece of filter paper over the crystals and pushing with a beaker or cork; the suction flask MUST be supported and sitting flat on the desktop. Dissolve it in hot ethanol, add water dropwise to reach the cloud point, and allow it to slowly crystallize.

Filter, dry, record the yield, and take the mp. If you do not have more than 2. If your instructor requests, run a tlc of the recrystallized product with known samples of benzoin and benzil for comparison of R f values. When you are satisfied that you have the product you want, you may dispose of the filtrate by first neutralizing with sodium carbonate, diluting with water, and flushing down the drain. We have recently started a programme to compare and contrast the chemistry of the corroles and corrins in order to elucidate the effect of the macrocyclic ring on the chemistry of Co III.

In this preliminary communication we report on the synthesis of several novel corroles which we have obtained in our exploration on the way to the synthesis of a biomimetic for aquacobalamin vitamin B 12a , which we will report on elsewhere.

Results and Discussion. We compared the synthesis of a simple triaryl corrole, 5,10,triphenylcorrole TPCrl , using the 'one-pot' synthesis method described by Paolesse, 6,9 a modification of the Lindsey method 19 which is a standard method for the synthesis of porphyrins, and the solvent-free approach of Gross.

In the Paolesse approach 20 mmol scale benzaldehyde and pyrrole 3 mole equivalents were dissolved in acetic acid and heated under reflux for three hours. The black precipitate produced was purified by column chromatography. Although NMR spectroscopic analysis indicated the presence of both 5,10,15,tetraphenylporphyrin TPP and TPCrl, we were unable to separate the very small amount of corrole from the many other unidentified products produced in spite of using a wide variety of solvents for the chromatography.

The Lindsey method 19 for porphyrin synthesis was modified by altering the ratio of pyrrole:benzaldehyde from in the typical Lindsey approach to in an effort to favour corrole over porphyrin formation.

The pyrrole and benzaldehyde were added to chloroform in the presence of catalytic BF 3 -Et 2 O under an argon atmosphere. After one hour, DDQ was added and the reaction mixture was stirred for a further hour. Two polymorphs of TPP were obtained and their structures determined by X-ray diffraction methods.

Not unexpectedly, the solvent-free approach of Gross 7 and co-workers was unsuccessful as the aldehyde used was not derivatized with an electron-withdrawing functionality. The reaction was performed on a 2. As none of the methods appeared viable for the reliable synthesis of corroles in a reasonable yield, we turned our attention to Gryko's water:methanol solvent system in the presence of a catalytic amount of HCl.

A small amount of TPP was also obtained. The corrole was identified by its UV-vis spectrum 25 Fig. S1 of the Supplementary Material with the Soret band at nm and a shoulder at nm, and the four bands in the visible region, characteristic of metal-free corroles and porphyrins, at ,, and nm.

The three pyrrolic protons present in the inner core of the macrocycle were observed up-field at Coupling of NMR signals was only evident at very low concentrations of corrole ca. S6 of the Supplementary Material. The first, of TPCrl itself, was crystallographically identical to that previously reported; 26 the second exists as a TPCrl hexane solvate.

S2 of the Supplementary Material. The molecules pack in a layered structure Fig. S3 with nearest corrole neighbours approximately 3. Table S1 of the Supplementary Material gives the bond lengths and bond angles in the molecule. As discussed in Experimental below, the presence of ordered, disordered and possibly partially absent hexane solvent made a structure solution quite difficult.

S4 of the Supplementary Material shows the hex-ane solvent channels of the structure. In the solvent-free crystal structure of TPCrl, the corroles also pack parallel to nearest neighbours, but the distance between the mean planes of the corrole N atoms is a little larger 3.

This type of distortion is also observed in porphy-rins, and is referred to as a saddled sad distortion. S1 of the Supplementary Material. The presence of the large triphenylphosphine ligand ensured that the macro-cycles did not aggregate in solution or in the solid state. As a result, the 1 H NMR spectrum consisted of well-resolved multiplets. We explored the scope of Gryko's water:methanol method by synthesizing a corrole with a strongly electron-withdrawing group in the phenyl substituents, 5,10,tri 2-nitrophenyl corrole, TNPCrl.

The yield was only 4. We were unable to crystallize the corrole and had to resort to spectroscopic evidence to confirm its identity. The 13 C NMR spectrum showed resonances at The one-pot synthetic methods available were of limited utility for our purposes. In our experience, yields tended to be low and purification was often problematic.

The method is also limited in its scope in that the product obtained would have three identical substituents at the meso positions Scheme 1. We therefore turned our attention to the step-wise approach of Scheme 2 which proceeds though a dipyrromethane intermediate, and in particular the route involving a bilane intermediate.

The synthesis of a dipyrromethane can produce trimers, tetramers and higher oligomers. We found that the formation of the longer chain species was limited, but not avoided, by using a large excess of pyrrole 40 mole equivalents as well as a short reaction time 15 min. There were no aldehyde signals from benzaldehyde in the NMR spectrum; the methine proton was observed as a singlet at 5. The positions of the pyrrole signals were shifted up-field shift with three signals observed at 6.

There is also a characteristic singlet at4. The development of a corrole model for vitamin B 12a requires the incorporation of a tail in the corrole which terminates in an aromatic N-donor ligand capable of coordinating Co III. To test the feasibility of this, we set out to design and synthesize a corrole with a bulky substituent at the 10 position.

Recrystallization of the resin from an aqueous solution of hydrochloric acid yielded colourless needle-like crystals. The product, 2- benzamido benzylben-zoate,was identified using 1 H NMR; the hydroxyl proton which was present at 4.

In addition, the methylene proton signal shifted from 4. The signals in the aromatic region integrated for 14 aromatic protons, indicating the incorporation of a third phenyl ring. The presence of the aldehyde was confirmed by the down-field aldehyde proton signal at N -[2- Hydroxymethyl phenyl]benzamide, N - 2-formyl-phenyl benzamide and 2- benzamido benzyl benzoate were all found to be crystalline and polymorphic.

The polymorphism resulted from differences in the van der Waals associations in the solid state, as discussed elsewhere. The unit cell is shown in Fig. S5 of the Supplementary Material. The crystallo-graphic details are listed in Table 1.

The bond lengths and angles are given in Table S2 of the Supplementary Material. The corrole itself, as observed with TPCrl see above is sad distorted, presumably to accommodate the three NH protons in the macrocyclic cavity. Two corrole molecules are packed in a face-to-face manner about a centre of inversion in the unit cell Fig. The mean planes through the four N atoms of each corrole are parallel to each other, separated by 3.

These planes are themselves parallel to the first plane of a neighbouring pair of molecules, at a distance of 3. Thus, the corroles stack along the a axis. Translation of these stacks along the b and c axis results in a layered structure. We observed the same concentration-dependent line-broadening effects in the NMR as with TPCrl, suggesting that this aggregation persist in solution Fig.

S12 of the Supplementary Material and the solution structure is therefore probably similar to that shown in the solid state. Summary and Conclusions. The feasibility of synthesizing a corrole-based vitamin B 12 analogue has been established, firstly with the synthesis of simple corroles, including 5,10,triphenylcorrole, 5,10,tri 2-nitrophenyl corrole and 4-methoxyphenyl -5,diphenyl-corrole.

The synthesis of [2- benzoylamino phenyl]-5,diphenylcorrole suggests that a large, bulky meso substituent can be incorporated into the corrole with no loss of stability or significant decrease in yield.

The corroles prepared were synthesized using Gryko's metha-nol:water procedure. This was confirmed by the close intermolecular packing of the corroles in the solid state in crystal structures of 5,10,triphenylcorrole and [2- benzoylamino phenyl]-5,diphenylcorrole.

The synthesis of a vitamin B 12 corrole analogue will be reported elsewhere. Unless otherwise indicated, all syntheses were conducted in a dark room under dim red light conditions.

Synthesis of 5,10,Triphenylcorrole TPCrl. The Paolesse Approach 6. Freshly distilled pyrrole 4. The stirred colourless solution was refluxed for 3 hours and became dark green-black.

After cooling to room temperature deionized water mL was added and a precipitate was filtered off. Solid NaCl was added to the filtrate to produce a further precipitate. The combined precipitates were separated by silica gel flash chromatography with dichloromethane as eluent. Modified Lindsey Method. Freshly distilled pyrrole 0. An immediate colour change from colourless to yellow-green was observed. The flask was covered in foil and the reactuion mixture stirred at room temperature for 1 hour by which time the solution had turned orange.

DDQ mg, 0. The colour of the solution immediately changed to black. The reaction mixture was stirred for an hour at room temperature, then concentrated in vacuo. For standard numbering of porphyrins see Fig. S8 of the Supplementary Material. UV-vis nm, in DCM , ; sh ; ; ; ; The Solvent-free Method of Gross 7. A solution of freshly distilled pyrrole 0. The tar-like mixture was dissolved in dichloromethane 50 mL and oxidized with DDQ 0.

There was no evidence of the formation of a macrocycle in the 1 H NMR spectrum. Gryko's Synthesis in Water:Methanol 8. The mixture was stirred at ambient temperature for three hours after which time an orange precipitate had formed. The reaction mixture was extracted into chloroform. The red organic layer was washed with water twice, dried with Na 2 SO 4 and diluted with chloroform to a volume of mL. The black reaction mixture was allowed to cool to room temperature and concentrated in vacuo.

The crude product mixture was separated by column chromatography on flash silica gel with dichloromethane as eluent. The corrole-containing fractions identified using UV-vis spectroscopy were combined and evaporated to dryness in vacuo. A dark purple-black powder was obtained For standard numbering of corroles see Fig S9 of the Supplementary Material. The reaction was monitored using UV-vis spectroscopy. The solvent was evaporated in vacuo and the crude product was separated using column chromatography on flash silica gel with dichloromethane as eluent.

The red fraction was collected and concentrated in vacuo. The solid was recovered 0. The reaction mixture was stirred at ambient temperature for three hours after which time an orange precipitate had formed. The crude product mixture was separated by column chroma- tography on flash silica gel with dichloromethane as eluent.

The corrole-containing fractions identified using UV-vis spectros-copy were combined and evaporated to dryness in vacuo and a green-black solid was obtained 0. UV-vis nm, in DCM : ; sh ; ; ; Routes to Corroles via a Dipyrromethane and a Bilane. Preparation of 2,2- Phenylmethylene bis 1H-pyrrole dipyrromethane Benzaldehyde 0. The solution was stirred at room temperature for 15 min and then diluted with dichloromethane mL and washed with 0.

The organic layer was dried with Na 2 SO 4 and concentrated in vacuo to remove the excess pyrrole. The crude solution was cooled to room temperature then filtered using a Buchner funnel. The reaction flask and filtered solid were washed with methanol leaving behind shiny purple crystals.

The filtered solid as well as the solid remaining in the reaction flask were then washed with methylene chloride into an oven dried and pre-weighed round bottom flask. The solution was concentrated to dryness then weighed for yield determination. The reaction is simple and reliable. The challenge is achieving optimum yield. Reactant concentrations and reaction time are very important. For optimal yield, reactant concentration should be approximately 0. Although the Adler synthesis of TPP constitutes a quick and reliable method for synthesizing tetraarylporphyrins, it is by nature a very low yielding reaction.

Inspection of the mechanism for porphyrin formation reveals why. If available, dry propionic acid gives greater yields. Make sure both pyrrole and benzaldehyde are fresh and in high purity.