Interview Questions for Testing Synthetic Organic Chemistry Technical Expertise

About the Nature of the Test

One objective of these questions is to provide recruiters who are looking for new employees who must have synthetic chemistry laboratory skills, quick access to questions pertinent to real laboratory skills and knowhow. 

Questions target what employers might ideally wish candidates to already know when starting employment. The recruiter can either select questions that most closely reflect the anticipated work area or can select questions at random so as to be sure that the candidate has not selectively prepped for the interview. It is not expected that any candidate will be able to answer all these questions. 

More questions are provided than any candidate could be asked or would have time to answer. This is so that a candidate cannot memorize answers to just a few specific questions and so falsely convey that his/her knowledge is more comprehensive. 

Sadly, resumes can no longer be taken as totally truthful. False claims are common; some verification of knowledge and experience is essential and that testing needs to be rapid fire.

Although your own questioning will always remain the most pertinent, supplementing with some of those proposed below can broaden the basis for what is a heavy responsibility.

This blog article has a second purpose. These same questions can guide prospective employees towards the entire range of skills and knowhow that perhaps is being sought.  Candidates can use the questions to broaden their job preparation. Answers or partial answers can be found by searching keywords with Google narrowing answers down in many cases by including the keyword KiloMentor in their search or by searching using the search tool in the KiloMentor blog itself.

Questions are selected not only to elicit particular information but also to initiate a technical conversation between interviewer and candidate. Sometimes questions assess how a candidate reasons from what is provided.

Candidates are well advised to immediately admit to the interviewer that they should acknowledge questions they really aren’t confident about some questions.  This will save time and provide the interviewer with more time for you to show your strengths.

Questions are targeted towards preparative organic synthesis, not analytical work. Although there exist preparative variations of analytical methods, ie preparative HPLC, preparative GC, these are never the answers sought here. When one is asked about useful methodologies they most often relate to rugged scaleable methods. The questions range between simple and very difficult. Unambiguous communication of subtle distinctions relating to science is an important skill for working in teams. If you believe that more information is needed for an answer, specify what is needed, how you would obtain it, and why you consider it essential for the answer.

Test Questions

With reference to fractional distillation, what is a 'pig'?

In words or a sketch, describe a kugelrohr assembly.

What is the meaning of 'star', with reference to a round-bottomed flask?

With the assistance of a simple diagram, show what is meant by 'R_f' in thin-layer chromatography?

Put the following solvents in approximate order of the Eluotropic series, ending with water: acetone, benzene, carbon tetrachloride, chloroform, cyclohexane, dichloromethane, diethyl ether, ethanol, ethyl acetate, hexane, methanol, n-propanol, toluene, trichloroethylene, water. What factor most influences this series's order?

What does 'quarantine' mean in the context of process validation and chemical processing?

What is the difference between 'reprocessing' and 'reworking' with respect to process validation?

What is 'inverted filtration'? When is it used? How could you prepare such a filter for laboratory-scale use from common laboratory equipment and materials?

Why is it important in 'fractional distillation' to have the fractionating column precisely vertical for the best results?

What is a  'unimolecular reaction'?

For a bimolecular reaction, what decrease in reactor volume would be predicted to give a doubling of the reaction rate?

As part of a separation, you have immobilized a substance that contains both a primary amine functional group and a carboxyl functional group on a cationic exchange resin in the protic form. What solvent systems would you contemplate for eluting this substance?  Put another way what properties should this elution solvent have?

Explain what 'lyophilization' is.

What very pragmatic advantage would lyophilization have over stripping solvent on a  rotary evaporator?

'Inverted filtration' refers to which of the following:

1. A chemical operation where a slurry is applied to a filter surface through the stem of the filter.
2. Filtration of a reaction mixture before beginning the reaction.
3. Filtration of a partially charged reaction mixture, before starting a reaction, in order to obtain a purer solid product at the end.
4. Filtration using a filter stick.
5. Filtration by the application of pressure rather than vacuum.

A 'unimolecular reaction' is:

1. Another term for a rearrangement
2. A reaction such as 1A + 1B giving 1 A-B in which all the coefficients are 1.
3. A reaction performed using one mole of substrate
4. A reaction in which the rate is directly proportional to the substrate only.

Name two reagents for destructive visualization of spots on silica TLC plates?

If you spill mercury metal on the floor, what methods could you practically use to clean it up?

Draw an equipment setup for doing steam distillation at a lab scale? What kinds of compounds is it used to separate?

What characteristics of components of a mixture should suggest steam distillation as a possible treatment?

What is the temperature of the steam in a steam distillation?

You have a hexane solution that contains your crude product dissolved in it but the solution is black in colour. The chemical structure of your target product does not have any strong chromophore nor does it contain a metal. Propose 4 or 5 suggestions that might remove the colour or substantially reduce the colour's intensity.

You need to find out how to identify spots on a TLC plate containing a particular functional group. Where would you look to find an appropriate visualizing agent? Alternately, what search terms would you use to search for this information so that you would end up with only a few good answers?

How could one quickly, without entering the laboratory, identify a reaction that is likely to be highly exothermic from its balanced chemical equation?

You are trying to dry an organic solid in a drying oven, but the weight does not seem to level off. What might be happening?

You have freeze-dried a solution containing a polar organic solute and some inorganic sulfate salts. What method would you try to easily separate the organic solute from the sulfate salts?

Draw the structure or provide the trivial name for a reagent that can be used to separate

1. Aldehydes or ketones from non-carbonyl compounds
2. Aldehydes from ketones
3. Aldehydes or methyl ketones from other carbonyls

Name three functional groups that could be present in an organic molecule of five carbon atoms that is insoluble in concentrated sulfuric acid?

Finely divided anhydrous calcium chloride when stirred in hexanes with a drop of ethanol as catalyst will often form solid complexes with compounds containing what functional group?

What reagent reacts reversibly with both methyl ketones and aldehydes to give derivatives which are often water-insoluble?

What is the Hinsberg test? What classes of functionality does it distinguish between and how is each functional group sub-type distinguished?

Do you know a reagent that reacts as a Hinsberg reagent but allows the original functionality to be regenerated?

If a compound that you wish to purify has too high a boiling point to be conveniently distilled, what common derivative class should you consider making to lower its boiling point?

In distillation, what is a chaser?

In distillation, what is a boiling chip?

List ways to prevent bumping during vacuum distillation.

What is the difference between evaporative /molecular distillation and regular fractional distillation?

When a high boiling oily organic is distilled from one glass bulb into an adjoining glass bulb using a mechanical device that simultaneously applies vacuum and rocks the bulbs, what is the apparatus called? Why is the apparatus rocked back and forth?

What is the chemical structure of the functional group called oxime?

What solid derivatives of alkynes do you know?

You are conducting a reaction in which reagent A is mixed with a substrate B at 50°C in a variety of  solvents. The reaction mixture consistently becomes black and a tar is formed. What kinds of changes might you make to improve the situation? Give reasons for your plans. Make your answers as generally applicable as possible. If you make assumptions say what these are.

What are simple things one should do if one is planning to scale-up a transformation that might be exothermic?

Neal G. Anderson, in his book, Practical Process Research & Development, particularly suggests avoiding as much as possible changes in the oxidation states of the process substrate. What reasons would there be for this advice?

During the workup of a reaction, you are faced with an emulsion between a toluene solution and a dilute aqueous solution. The reaction is one element of a process scale-up. What methods can be used to break the emulsion? If you are already in the plant what methods are more preferred and why?

What is a “kill solution” in the context of chemical process development?

Which of the following solvents would be problematic for use at scale in a plant setting?
pentane, heptane, carbon disulfide, diethyl ether, methyl t-butyl ether, diisopropyl ether, di-n-butyl ether, benzene, N, N-dimethylaniline, carbon tetrachloride, toluene, chloroform, isopropyl acetate, 2-methoxy ethanol, HMPA, ethylene glycol

What is a thermomorphic solvent?

What is the special difficulty in switching from one solvent to another as part of a reaction step in plant or pilot-plant equipment that is no problem when working at a laboratory scale?

Propose a process sequence for switching from dimethylformamide solvent to methylene chloride without a water drown out?

Describe solid-liquid extraction. What are its advantages? Give examples of its use for functional group separations.

How does dry column chromatography differ from regular chromatography? What would be some of the advantages of this technique for separating small quantities of pure compounds?

You want to separate two substances in which the most prominent difference between them is that one compound contains an aromatic ring while the other does not. What chromatographic adsorbents would be the best candidates for the separation? Do not just propose any adsorbent with low loadings and long columns.

You have been delivered a procedure for a chemical transformation that works in high yield and good recovery. The problem is that when this is scaled up in the available reactor, not enough material can be produced. What do you do to improve the throughput? What problems are likely to arise when you try the solution?

What are scavenger resins? Give an example of the use of one.

Separation of a few milligrams of pure compound is being tried on an analytical HPLC column using analytical separation conditions but as the injection size is increased the detector shows peaks quickly overlapping. Can anything be done?

For what is AgNO3 on silica gel used in the laboratory? 

What is co-distillation? Why would one use this technique?

You have a thermally stable but almost insoluble compound that is not adequately pure. The desired compound is the main component. Product and impurities can be separated analytically by TLC on silica gel, but only after multiple elations because the Rfs are almost zero. How can the chromatography apparatus be changed to facilitate in the laboratory the separation using a reasonable volume of solvent?

You need to know how to identify the spots on a TLC plate. Where would you look to find an appropriate visualizing agent? On-line what keywords would you use? 

Do you have experience doing substructure searching in chemical databases?

What is Claisen’s alkali? What is its most important use?

What is a more efficient way than washing with water to remove traces of pyridine from diethyl ether solution?

If a multifunctional compound that you wish to purify has too high a boiling point to be practically distilled, what common derivatizing agent should you think of to lower the boiling point?

In chemistry what is a ‘chaser’?

What is extractive distillation? What kind of separation problem is it helpful with?

What is the difference between evaporative/molecular and fractional distillation?

What is ‘phase shifting’ in chemistry?

You have equal volumes of pyridine and water mixed together; is there a simple way to achieve rough phase separation to recover most of the pyridine?

One way to separate compounds with alcohol functional groups from compounds that are not alcohols by extraction is to prepare an alcohol derivative which can be extracted into an aqueous phase and then subsequently reform/reconstitute the alcohol. Describe methods for separating alcohols from non-alcohol by way of extractable and reversible derivatives.

Suppose you are asked to resolve the compound 1-phenyl-1-(2’-bromophenyl)prop-1-yn-1-ol.

First, What is the structural formula of this compound? Second, what actions would you take to as expeditiously as possible, carry out the resolution?