Crystallization solvent testing

The habit of pharmaceutical compounds has been used for purposes of identification, although the method can only be reliably used when the crystallization solvent used to generate the test crystals is carefully controlled. Since the faces of a crystal must reflect the internal structure of the solid, the angles between any two faces of a crystal will remain the same even if the crystal growth is accelerated or retarded in one direction or another. Toxicologists have made extensive use of microscopy following multiple recrystallization, and they have developed useful methods for compound identification [5]. 

From what we see on the next page (properties) we can tell that codeine is not very soluble, so it stands to reason that this will be the last substance that will be eluted from the column. Acetaminophen looks the most soluble, so lets get rid of it first. Acetone looks like a good choice, but its hard to tell because the Merck Index did not say if the other substances are soluble or insoluble in acetone. Try a little and see what types of crystals appear upon evaporating off the solvent, test the melting point and see if it is exactly as stated for acetaminophen. If there are only two types of crystals then it may be easier to go ahead and elute these and then separate... 

Resolution of 3-aminopyrrolidine is reported in the hterature using diben-zoyltartaric acid via a 2 1 salt. We found that the (R)-enantiomer of the IN-Boc protected racemate could be crystallized in 32% yield and 99.5% ee from ethanol in a single crystallization with 0.25 mol equivalents of (R,R)-dibenzoyltartaric acid (Scheme 13.9). Other solvents tested gave poorer results. 

Anhydrous ethanol and ether a 1 +1 mixture of these solvents does not dissolve anhydrous barium nitrate or barium chloride (distinct from strontium and calcium). The salts must be heated to 180°C before the test to remove all water of crystallization. This test can be applied for the separation of barium from strontium and/or calcium. 

Picking a Solvent. To pick a solvent for crystallization, put a few crystals of the impure solute in a small test tube or centrifuge tube and add a very small drop of the solvent. Allow it to flow down the side of the tube and onto the crystals. If the crystals dissolve instantly at room temperature, that solvent cannot be used for crystallization because too much of the solute will remain in solution at low temperatures. If the crystals do not dissolve at room temperature, warm the tube on the hot sand bath and observe the crystals. If they do not go into solution, add a drop more solvent. If the crystals go into solution at the boiling point of the solvent and then crystallize when the tube is cooled, you have found a good crystallization solvent. If not, remove the solvent by evaporation and try another solvent. In this trial-and-error process it is easiest to try low-boiling solvents first, because they can be removed most easily. Occasionally no single satisfactory solvent can be found, so mixed solvents, or solvent pairs, are used. 

Eor each of the three solvents (methyl alcohol, water, and toluene), describe the results from the tests for selecting a good crystallizing solvent for fluorene. 

Purify Compound 1 by crystallization. See "Testing Solvents for Crystallization," Technique 11, Section 11.6, for instructions on how to determine an appropriate solvent. You should try 95% ethanol and xylene. After determining the best solvent, crystallize the compound using a hot water bath at about 70°C for heating to avoid melting the solid. Identify Compound 1 using some or all of the techniques given next in the section "Identification of Compounds."... 

Write out a complete procedure by which you synthesized and isolated Compounds 1 and 2. Describe the results of your experiments to determine a good crystallization solvent for both compounds. Draw the structures of Compounds 1 and 2. Give all melfing-point data and results of other tests used to identify the two compounds. Identify significant peaks in the infrared spectrum and proton/carbon NMR spectra. Show clearly how all these results confirm the identity of the two compounds. Write a balanced equation for the synthesis of Compounds 1 and 2. What type of reaction is this Propose a mechanism for the reaction. Determine the percentage yield of each of the compoimds. 

Crystal tests require no specialized equipment. One or a few lichen fragments are placed on a microscope slide and the lichen substances present extracted by dropwise treatment of the fragments with a suitable solvent, usually acetone. After evaporation of the solvent, the fragments are removed, leaving a more or less crystalline residue of lichen substances on the slide. A drop of a suitable crystallizing solvent mixture is added to the residue and a coverslip added. The slide is heated gently over a tiny flame or on an... 

The catalyst precursor decomposes at a lower temperature under reaction conditions, and the catalyst is more active when normal or isobutanol is used as the organic solvent. Tests under reaction conditions show that maleic anhydride begins to form at 388°C, when the precursor decomposes. A final step of crystallization takes place as maximum conversion is reached at 390-400°C. The active catalyst has the same particle morphology as the precursor when examined by scanning electron microscopy. ... 

When crystallisation is complete, the mixture of crystals and crude mother-liquor is filtered at the pump, again using a Buchner funnel and flask as described on p. 10, and the crystals remaining in the funnel are then pressed well down with a spatula whilst continual suction of the pump is applied, in order to drain the mother-liquor from the crystals as effectively as possible. If it has been found in the preliminary tests that the crystalline material is almost insoluble in the cold solvent, the crystals in the... 

The oxime is freely soluble in water and in most organic liquids. Recrystallise the crude dry product from a minimum of 60-80 petrol or (less suitably) cyclohexane for this purpose first determine approximately, by means of a small-scale test-tube experiment, the minimum proportion of the hot solvent required to dissolve the oxime from about 0-5 g. of the crude material. Then place the bulk of the crude product in a small (100 ml.) round-bottomed or conical flask fitted with a reflux water-condenser, add the required amount of the solvent and boil the mixture on a water-bath. Then turn out the gas, and quickly filter the hot mixture through a fluted filter-paper into a conical flask the sodium chloride remains on the filter, whilst the filtrate on cooling in ice-water deposits the acetoxime as colourless crystals. These, when filtered anddried (either by pressing between drying-paper or by placing in an atmospheric desiccator) have m.p. 60 . Acetoxime sublimes rather readily when exposed to the air, and rapidly when warmed or when placed in a vacuum. Hence the necessity for an atmospheric desiccator for drying purposes. 

Either pure aqueous or aqueous/solvent solutions work. It is entirely up to the preference of the chemist as to which one they use. Just to make one feel more secure, there is a little test one can do with the bisulfite solution to see if they got it right. Just put a little of that ketone known as acetone into the saturated solution and watch the crystals grow. Isn t it nice how chemistry works ... 

So now we have this solvent containing ketone, dried with MgS04... Not being able to vac-distill today, took about 50 mis of solvent/ketone and placed in beaker on stir plate and boiled off the solvent. The resulting oil was a nice reddish-orange color. Had a very unique smell too. Took about 2 grams worth of this ail, added to a test tube containing a saturated solution of sodium bisulfite... In less than 60 seconds the oil precipitated into a whitish yellow mass (very similar to what acetone would do if added to a bisulfite solution). Never had this quick of a crystallization. Not... 

Chemical Resistance of LGPs. Ceitain liquid crystal polymers (eg, Vectra) have extremely high chemical resistance to a variety of aggressive chemicals and solvents. Table 18 shows the chemical stabiUty of Vectra test-bars to various agents (244). 

To date, a number of simulation studies have been performed on nucleic acids and proteins using both AMBER and CHARMM. A direct comparison of crystal simulations of bovine pancreatic trypsin inliibitor show that the two force fields behave similarly, although differences in solvent-protein interactions are evident [24]. Side-by-side tests have also been performed on a DNA duplex, showing both force fields to be in reasonable agreement with experiment although significant, and different, problems were evident in both cases [25]. It should be noted that as of the writing of this chapter revised versions of both the AMBER and CHARMM nucleic acid force fields had become available. Several simulations of membranes have been performed with the CHARMM force field for both saturated [26] and unsaturated [27] lipids. The availability of both protein and nucleic acid parameters in AMBER and CHARMM allows for protein-nucleic acid complexes to be studied with both force fields (see Chapter 20), whereas protein-lipid (see Chapter 21) and DNA-lipid simulations can also be performed with CHARMM. 

One milliliter each of the borneol solution and the oxidizing solution are mixed in a test tube and briefly shaken. A TLC slide is spotted with the borneol solution, the camphor solution, and the ether layer of the reaction mixture. Spotting is done by means of a capillary melting point tube used as a dropper and filled with a 5 mm sample. The slide is developed in a wide-mouth jar containing a filter paper liner and a few milliliters of chloroform (Fig. A3.20). After development (the solvent front rises to within 1 cm of the top), the slide is removed, the solvent is allowed to evaporate, and the slide is placed in a covered wide-mouth jar containing a few crystals of iodine. The spots readily become visible and the progress of the reaction can easily be followed. With periodic shaking, the oxidation is complete in about 30 minutes. 

For the evaluation of the response of the sensor, we selected several vapors of different polarity. The vapors included water (H20), acetonitrile (ACN), toluene, and dichloromethane (DCM). Solvent polarity and refractive index of tested vapors are listed in Table 4.346 47. The spectral range for the evaluation of the vapor responses of the colloidal crystal film was selected as 700 995 nm, which covered only the fundamental Bragg diffraction peak on the (111) planes of the colloidal crystal film to further reduce effects from possible stacking defects in the film as suggested in the literature44. 

---