Organic synthesis: Practical methods and procedures

Organic synthesis: Practical methods and procedures

Lessons

In this lesson, we will learn:

  • The practical techniques used to convert reactants to products
  • The practical techniques used to isolate products of chemical reactions.
  • The range of equipment and lab safety measured used in organic synthesis.

Notes:

  • There has been very little talk about this so far, but a big part of organic synthesis is the practical method. Chemists need to set up, run and clean up chemical reactions safely and efficiently. They need to know things like:
    • How can we make sure reactants react and don’t get wasted?
    • How are we keeping the conditions ideal for the reaction?
    • How do we isolate our product out from any side products, solvent or unreacted starting material?
    • What are the possible risks associated with this reaction (chemical burns, fire, gas etc)?
    • What safety measures must be there to reduce the risk of harm?
    It is a bit more complicated than “wear goggles and gloves at all times”.

    This lesson lays out the practical techniques in order of how they might appear in a typical organic reaction – starting with you getting your equipment set up, to doing the reaction, to isolating your product in a movable state, to testing it.

  • Quickfit glassware is a major brand of heat-resistant glassware used by chemists. The pieces are numbered/coded, fit together easily and use clips to fasten for the best fit. The equipment has parts that can be used in a variety of different practical methods/reactions.
    This is a simple example for scientists sharing and communicating their results to keep equipment standardised. It is just one more thing to be kept as a control, so the quality or type of equipment used won’t be the cause of different experimental results.

  • Heating under reflux is a very useful practical technique for running your reaction when you have volatile compounds with low boiling points.
    Reflux improves reaction safety and yield.
    • The reaction mixture containing anti-bumping granules is in a round bottom flask with a reflux condenser attached at the top. The granules prevent the mixture boiling violently. If the reactants start evaporating, the vapours pass through the condenser.

    • Cold water flowing around the condenser causes any reaction vapours to condense back into the liquid mixture in the flask below. The water flows in at the bottom and out at the top to prevent air pockets forming in the condenser.

    This recycling of reaction vapours stops any reactants (or products!) escaping, so your product yield improves. This is better than just sealing your vessel which could cause it to explode.
    It also helps safety – it’s always better to reduce the amount of hot chemical vapours that escape into a lab!

    Generally, you should suggest using reflux whenever your reaction contains substances with a boiling point below 100°C. This includes products! You don’t want to make your product only for it to evaporate out of the flask.
    See the image below for a summary.

  • Once the reaction is completed, you can use distillation to separate the product you want from the solution.
    Distillation works a little bit like reflux, except the reflux condenser is set up to let the vapours escape the flask but get collected as a liquid. We just turn it on its side pointing down!
    Using it this way, if we control the temperature we heat the flask at, we will separate substances by their boiling point.
    • Connect the finished reaction mixture to the distillation apparatus via a still head with a thermometer. A still head is a T-shaped piece of glassware specifically used in distillation; it will measure the temperature of the vapours at they are passing into the distillation condenser. This is important – the thermometer bulb should sit level with the bend of the still head. This is the temperature that the vapours will be as they condense. You want it at or near the boiling point of your product but no higher! Any higher and you risk collecting impurities that aren’t your product.

    • The vapours condense in the tube and are collected as a liquid at the bottom, separate from the reaction flask. Just like in reflux, the vapours condense because cold water surrounds the condensing tube. The difference is because it’s tipped diagonally down, instead of flowing back into the reaction flask, it’s collected out the other side.

    Distillation is useful when you know the boiling point of your product and any side products or solvent involved – there should be a fair gap between the boiling point of what you want and what you don’t so that you actually isolate your product.
    See the image below for a summary:

    IMAGE OF DISTILLATION APPARATUS WITH STILL HEAD DRAWN PROPERLY

  • Recrystallisation purifies our product when the reaction is finished and you have your product, but there might be impurities present.
    In short, it exploits temperature and solubility to get all the product in one place: first dissolved in a hot solution, then as crystals coming out of a cold solution.
    • First, dissolve the product in the minimum amount of hot sparingly soluble solvent. The solvent should be hot to increase solubility and dissolve as much product as possible. It should be sparingly soluble so that when it cools down, the product will come out of solution. Activated charcoal can be added to remove coloured impurities too.

    • The product solution is then quickly filtered, a simple paper/gravity filter will do. This needs to be done quickly so that any undissolved side products is filtered out, while the solvent is still hot so we can be sure our product isn’t coming out of solution yet.

    • Once filtered the solution is allowed to settle and cool down in an ice bath. During this time, the product will crystallise out of solution – lower temperature decreases solubility. This is why it has to be only sparingly soluble, otherwise it won’t crystallise out. During this time any soluble impurities will be left in the solution.

    • Finally, the mixture is put under a vacuum filter and washed with cold solvent to collect the crystals and discard the filtrate. You should be left with purified crystals of your product and any soluble or insoluble impurities removed at some stage of this process.

    Recrystallisation is generally used with most organic reactions when the product is a solid at room temperature, especially if there are possible side products. If you know what your product is, you can find out what it is sparingly soluble in by looking in a data book or online. This is then just an opportunity to get a purer, higher-quality product!
    See the image below for a summary:

  • If your product is a liquid at room temperature, you won’t be able to use recrystallisation to collect your product crystals - the product won’t be crystals!
    For these products, after doing a distillation, you could still have impurities in the mixture. It could be organic side products or aqueous impurities like salts. To remove these, you need to do a solvent extraction to separate your product by its solubility. You do this in a separating funnel. See the image below:
    • In your separating funnel you have an aqueous layer (water) and an organic layer where an organic compound is the solvent. One of these layers will contain your product (is it more soluble in water or organic?) and the other is there to remove impurities. Which layer is on top or bottom depends on density (which organic solvent are you using?)
    • With a stopper at the neck, turn it upside down and shake the separating funnel, opening the tap afterward to relieve pressure. Do this several times and then let the mixture settle and you will see the two layers separate.
    • Decant the layers into two separate conical flasks. At this point, which ever layer contains your product should be put back into the separating funnel for another extraction by adding more of the opposing solvent layer. You are trying to get rid of as much impurities as possible!

    At this point you have purified by solubility as much as you can, so from here you can add magnesium sulfate (MgSO4) to remove trace water, filter and run another distillation.
    For example, you have got rid of any aqueous salts in your reaction mixture, and now have just your organic product and unreacted starting material remaining that can be separated by boiling point. This distillation can be more precise with less ‘junk’ in the distillate!

  • Once you have your pure isolated solid product, you can test the product purity by melting point analysis.
    All unique chemical compounds have unique melting points – let’s say for example substance X melts at 100°C. A pure sample of substance X will melt precisely at 100°C, but any impurities will not have the same melting point, so their presence will cause the sample to melt at a range around 100°C.
    In short, the smaller the melting point range, the purer the product sample.
  • Introduction
    Practical methods in organic synthesis
    a)
    Introduction to practical methods

    b)
    Reflux.

    c)
    Distillation.

    d)
    Recrystallisation.

    e)
    Solvent extraction.

    f)
    Melting point analysis.


  • 1.
    Understand the reasons for using various practical laboratory techniques.
    Below is a diagram of reflux apparatus. There is one mistake and one important feature left out of the diagram.

    Identify and correct these, giving reasons for them.

  • 2.
    Outline and describe practical methods for chemical reactions and product purification.
    Pentan-2-ol can be oxidised to pentan-2-one by acidified potassium dichromate under reflux.
    a)
    Draw a diagram with labels to show the practical setup of this reaction.

    b)
    The product mixture contains pentan-2-one and some unreacted starting material. The mixture needs to be distilled to isolate the product.
    • The boiling point of pentan-2-one is 101°C
    • The boiling point of pentan-2-ol is 119.3°C

    Draw a diagram of the distillation apparatus setup and describe a method to obtain a pure sample of the pentan-2-one product.