Todd:Guidelines

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Reaction Numbering
Reactions need to be given a unique identifier. The number takes the following form: Your Initials X-Y-Z where X is the reaction type, Y is the attempt number and Z is the page of your lab book where the reaction appears.

A reaction type means ‘starting material-arrow-product.’ If you are attempting a certain transformation of a particular starting material to a particular product, then any attempt at that reaction has the same reaction number, regardless of reagents. The reaction also has this number regardless of the outcome. It is the intention that counts. Stereochemistry of products is also important – if the intended stereochemical outcome is different, the reaction has a different number. The numbering of reactions is unique to you, you do not use the same numbers as previous people in the group even if you are repeating their work.

Attempt number just increases by 1 each time you do the reaction. Screening several different reaction conditions on small scale on the same page of your lab book can be named with ‘A’ ‘B’ ‘C’ after the full name if so desired, rather than exhaustively giving each reaction a different Y, so e.g. MHT 1-2-3A, MHT 1-2-3B etc.

Z is the page number of your lab book where the reaction diagram appears. This number stays the same if the reaction write-up extends over more than one page. In fact it is a good idea to begin each new reaction on the right hand-facing page of the book, allowing overspill at a later date.

Example. The first three reactions in MHT’s lab book are shown below. The first reaction here is the first in the lab book. This transformation is given the number ‘1.’ It is the first attempt at this reaction, and appears on page 1, hence it is called ‘MHT 1-1-1.’ The second reaction is the same transformation (remember, regardless of reagents), so also has X = 1. It is the second attempt, and appears on page 3 of the lab book, so has the identifier MHT 1-2-3. The third reaction is a different transformation, so has a different X, and this is the first time it has been done, so Y = 1, and has been entered on page 5 of the lab book, giving MHT 2-1-5.



It is a very good idea to keep a tally at the end of your book where you list each transformation separately together with the identifiers of all the attempts along with the yields in each case. Remember the identifier stays the same even if the yield is 0%.

For reactions that produce multiple products, and where those products are isolated e.g. by column chromatography, additional numbers may be needed, MHT 1-1-1/1, MHT 1-1-1/2 etc, and the relevant spectra and vials should be labelled as such.

Lab Book Write-up
DO NOT WRITE NOTES ABOUT WHAT YOU HAVE DONE ON LITTLE BITS OF PAPER

When writing your lab book, you should include all details, but in a concise manner. The reason for keeping a lab book is so that the people who come after you can understand and replicate what you have done. You are writing it for them, not for me.

Your lab book must be written in pen, not pencil. You must never remove or add pages. Mistakes must be crossed out lightly, so that they may still be read. Do not use white-out/Tippex. All lab book pages must be dated somewhere, and when complete, should be signed. Ideally periodically you should get another member of the group to sign and date your lab book pages.

Each new experiment must be assessed for safety. Instructions on how to do this are given in the School's safety handbook here where you can also download templates for doing risk assessments.

All relevant TLC’s must also be drawn in pen, and RF values given to two decimal places, as well as the solvent system used for each. (Drawing TLC’s allows you to throw away your TLC plates)

The write up should look something like this:



Points to note here:


 * The first line of the write up for each reaction contains a brief remark about the reason for doing the reaction, to aid your memory when you come to write up your work, e.g. ‘Scale-up of MHT 5-4-36’ or ‘MHT 7-4-98 at increased temp.’
 * Some information about where the chemicals have come from is given
 * Some incidental detail about what happened is given, and you have to judge what is useful and what is not. Unexpected things should always be included (e.g. ‘now-yellow’ above)
 * ‘Benzaldehyde’ is listed in the text with no quantities, because these have already been given in the reaction scheme above
 * References are given for the reaction. Here they are literature papers, but if the reaction has relevance to a previous reaction you have done (which is most of the time) then that unique identifier should be given here
 * Try to minimise use of the word ‘then.’ This word is often redundant
 * ‘Concentrated in vacuo’ implies hivac. ‘Concentrated under reduced pressure’ implies rotavap
 * When typing this up, the formatting has to be exactly right. There are spaces between quantities and units for everything except % and degrees C. So we write ‘3 h’ and ‘1 M’ but ‘49%.’ Remember also that millilitres are abbreviated ‘mL’ not ‘ml’

Sample Characterization
If you want to make a molecule, the first thing to do is check whether it’s been made before. Use SciFinder frequently (often you'll need to use it daily). You can access previously-used methods, characterization data etc. It’s the most important resource we have. Besides being able to search for literature examples of reactions you may be attempting, it's also a very rapid way to find characterization data for compounds you're making (from the "experimental properties" link).

If you want to know how to handle a reagent, check e-EROS online. All of the Chemistry databases are here

When you use a starting material for the first time, acquire a 1H spectrum of it to check its purity and to compare with your reaction product.

In general there are two kinds of characterization required for molecules before we can publish the work. The first is for known compounds, i.e. compounds previously synthesized either in the group or by others in the chemical community. For these compounds we require three pieces of characterization that match the literature (usually a 1H NMR, IR and low resolution mass spectrum). For crystalline solids we need a melting point and a comparison with the literature value, which can count as one of the three pieces of data. For enantiopure or scalemic compounds we require an optical rotation and a comparison with the literature value.

For novel compounds, we require the full level of characterization. This includes 1H and 13C NMR and IR spectra. We also need a low-resolution mass spectrum. For crystalline solids we require a melting point. If you have distilled a liquid, we require the boiling point. The ‘killer’ bit of characterization that finishes off the data is either a high-resolution mass spectrum or (better) an elemental (CHN) analysis (not both). For enantiopure or scalemic compounds we require an optical rotation and some indication of the level of enantiopurity - this must come from chiral HPLC or NMR shift reagent analysis.

For any compounds that undergo some form of further evaluation (e.g. biological evaluation) we need some assessment of purity, which is usually gained from comparison of melting points (for known compounds) or analytical HPLC analysis (for novel compounds).

RF values are important for internal purposes, but have questionable reproducibility between labs. Thus while we need these values in lab books and internal reports, we do not generally report them in publications.

Spectra should be kept in order of their unique identifier in folders. The identifier and structure should be written clearly so that someone browsing the file can locate the appropriate spectrum quickly. Think about the people who will come after you. Generally if you're asked to produce a spectrum, you should be able to find it in a few seconds.

For NMR spectra, expand regions of interest - typically maybe 3-4 expansions for a 1H, one aromatic and one alkyl for a 13C. For writing up the data you will need the exact J values for each well-defined peak, and an accurate J needs ppm values for the relevant peaks to an accuracy greater than 2 decimal places. You must make sure the integrals for peaks have horizontal start and end lines, so that the values are real. Draw the structure of the molecule on the front page of the spectrum. Assign the peaks. If the spectrum shows a byproduct, draw this structure also. If the spectrum shows an unidentified product, draw the intended reaction and product on the front page, and indicate that the spectrum does not show this product. (It’s all about putting yourself in somebody else’s shoes and asking yourself whether your spectra would be clear to them – no mental notes)

For publication purposes, we almost always require scanned copies of 1H and 13C NMR spectra for the supporting information. Thus you must examine and assign spectra very carefully to ensure that there are no ‘rogue’ peaks and no large solvent peaks. Obtaining clean NMR spectra and assigning them is the most important skill of the synthetic chemist. Once you've done all the above with your spectrum, you can show it to Mat.

Instructions for producing jcamp.dx files coming...

Report Write-up
Progress reports are due on the last days of April, August and December. Put these dates in your diary and plan ahead to get them in on time. If your report’s late, you will owe Mat one pint of Coopers Red. For each further 12-hour period that elapses, you owe Mat a further pint. That could get very expensive for you, and really great for Mat, but reports still need to be in on time.

Initially paper copies are required, Times New Roman, double-spaced, unstapled. Reports should be double line-spaced and double-sided, ideally with the facing page devoted to schemes. Mat does not want to correct English language mistakes. If you feel you might make such mistakes, ensure you have your report read by someone else before you give it to Mat. Obviously no part of your report should be copied/plagiarised from any source. Everything needs to be in your own words.

Once you've been through the report with Mat, and you've corrected the report, you should provide a corrected electronic copy that will be archived. The main purpose of the report is to summarize what you have achieved. However, these reports should contain everything that has gone through your chemical mind in the previous three months, and are useful places to record references and project ideas for the future. Time and effort spent on this is very helpful in minimizing the work involved in submitting publications. This is particularly the case for your descriptions of experimental work, and the documentation of spectra. Use the group characterization form to keep track of what characterization you have for a compound, and which experiments you did which generated a given compound.

Write-up check-list for reports/procedures:


 * Spaces between numbers and their units except for percentages and degrees C
 * NMR spectroscopy, mass spectrometry; spectrum vs. spectra
 * Compound numbers in bold
 * Minimization of the use of the word ‘it’; don't start sentences with the word 'this'
 * The words Figure, Scheme and Table capitalized in main body of text
 * Make sure your spellchecker is on, to catch simple typos and double spaces etc. Mat didn't get a PhD in order to correct dumb things.
 * "Dropwise", "portionwise" and "semisolid" are one word
 * If you use abbreviations for chemicals, these need to be added to an abbreviations section
 * Be consistent with descriptions of chemicals, e.g. DCM vs CH2Cl2
 * Don't just say you obtained "crystals" - give a description of what they look like, i.e. prisms, plates, stars or needles.
 * Stereochemical descriptors are italicized but their brackets are not, e.g. (S)
 * The N for nitrogen on the front of molecule names is italicized, e.g. N-benzylmethyl amine
 * In procedures (but not in the main body of a report/thesis/paper) shorten words when possible, e.g. rt for room temperature, h for hours, min for minutes. Use numbers rather than words when possible, e.g. 5 rather than five.
 * Reduce repetition if procedures are the same for multiple compounds, e.g. say things like "The procedure employed for the synthesis and purification was the same as for compound X, giving the amide as a white solid (mass, yield%)" or by writing a general procedure for a group of compounds and just listing the data for each compound in the same section.
 * Be consistent with accuracy. Thus within one preparation (but not necessarily within one report/paper) amounts should be reported with consistent accuracy. Usually this means reporting masses to three significant figures (e.g. 354 mg), and calculating moles to the same level of accuracy (e.g. 1.30 mmol - not 1.304658 mol, since this is more accurate than the mass measurement). But be sensible. Reporting concentrations of solutions used in work-up to three significant figures is clearly unnecessary, since nobody cares (e.g 0.5 N HCl is fine for a work-up, 0.507 N HCl is silly unless the solution is being used as a reagent).

Examples of experimental procedures

The way you write up a synthetic procedure should look a little like the lab book page above, but there are a few differences. The best way to see how to do it is to look at some recent theses, but here are some examples to give you an idea. Spot the difference!

Sample procedure which contains errors:

5.2.2	Selective mono-BOC protection of 1R,2R-diaminocyclohexane (16)14 Conc HCl (36%, 0.78 mL, 9.07 mmol) was added to MeOH (100 mL) at 0 °C, the mixture was stirred for 15 min and slowly added to a solution of 1R,2R-diaminocyclohexane (1.035g, 9.07 mmol) in MeOH (100 mL) at 0 °C. After the addition is complete, the mixture was allowed to warm to rt. Stirring was continued for 15 min at rt before adding water (30 mL). The resultant solution was stirred for another 30 min at rt followed by (Boc)2O (2.38 g, 10.88 mmol) in MeOH (25 mL) The reaction mixture was stirred for 1 h, concentrated in vacuo to remove MeOH. Un reacted diamine was removed by partitioning with diethyl ether (100 mL×3). The aqueous layer was treated with 2N NaOH until it became pH 10. The liberated free amine was extracted in to DCM (50 mL×4) and combine extracts were washed with brine (100 mL) dried over Mg2SO4 and solvents were removed in vacuo to obtain t-butyl ((1R,2R)-2-amino cyclohexyl)carbamate as a white sticky solid (1.6 g, 82%).

The same procedure after Mat has hacked at it:

tert-Butyl ((1R,2R)-2-aminocyclohexyl)carbamate (16)14 Conc. HCl (36%, 0.78 mL, 9.1 mmol) was added to MeOH (100 mL) at 0 °C. The mixture was stirred for 15 min and slowly added to a solution of (1R,2R)-diaminocyclohexane (6, 1.04 g, 9.07 mmol) in MeOH (100 mL) at 0 °C. The mixture was allowed to warm to rt. Stirring was continued for 15 min at rt before the addition of water (30 mL). The resultant solution was stirred for another 30 min at rt. (Boc)2O (2.38 g, 10.9 mmol) in MeOH (25 mL) was added. The reaction mixture was stirred for 1 h and concentrated under reduced pressure to remove MeOH. The solution was washed with diethyl ether (3 × 100 mL) to remove unreacted diamine. The aqueous layer was taken to pH 10 by the addition of 2 N NaOH and extracted with DCM (4 × 50 mL). The combined extracts were washed with brine (100 mL), dried over Mg2SO4 and concentrated in vacuo to give the protected amine as a white sticky solid (1.60 g, 82%).

Examples of experimental data

Novel compound:



Known compound:



It’s important you check write-ups against these examples.

Things to note for writing up characterization data:


 * NMR spectra peaks listed in increasing value and must be assigned.
 * 1H values given to two d.p., 13C to one.
 * 13C NMR frequency is one quarter of the 1H frequency for spectra acquired on the same machine. (Why?)
 * J is italicized; when there are multiple couplings, use ‘&’ to separate them and give the largest first, e.g. J 12.4 & 3.5
 * No space between value and H for integrals, i.e. ‘1H’ not ‘1 H’
 * Only give the large, important peaks for MS, and give % height for them.
 * HRMS should be correct to within 0.0008 for small molecules.
 * CHN should be correct to within 0.4%
 * Reference given after the name of the compound is for the procedure followed (if any) not necessarily for that particular compound. Thus a novel compound can have a reference for a general procedure that was followed.
 * Known compounds require a final "Spectroscopic data matched those in the literature." and a reference.
 * Molecular formula given for HRMS includes extra H for MH+.
 * AB quartets: these can be written in two ways. First (usual): 2.54 (d, 1H, J 17.4, PhCHHN), 2.65 (d, 1H, J 17.5, PhCHHN). Second (less usual, but cleverer): 3.45 (ABq, 2H, J 15.9, ν 79.5, PhCH2N) where the ppm value given is the midway point of the two doublets, and the ν describes the separation of the doublets in Hertz. The second way is described in Williams & Fleming.

When you leave the group, all your lab books and spectra remain in the department and all reports/write-ups need to be handed in digitally.

An Important Note about Correctly Referencing the Literature
It is very common for students, writing their first report, to make a simple but very important mistake in how they reference the literature. The point about referencing a paper is that that paper will give the reader more details about the thing you've just said. The point about referencing a paper is not so that the reader is taken to the paper where you got that statement from.

So for example, let's say that at the beginning of your report or thesis, you want to say "Acetyl CoA is an important molecule that plays an important role in many biological processes." A statement like this really needs a reference. There are three options for you. The first is to reference a review which is on the subject of acetyl CoA and its role in biological processes. The second is to reference some major research paper, or series of papers, which have demonstrated that acetyl CoA is involved in biological processes, and which have been cited by others many times. The third is to reference a research paper which has in it the sentence "Acetyl CoA is an important molecule that plays an important role in many biological processes" because that covers your ass. What's the best thing to do? 1 is better than 2, and you should NEVER do 3. The purpose is to direct the reader to a bigger source of information. If you did 3, and just reference some other paper that says something similar to what you're saying, then the reader has not been directed to a more comprehensive source, and has to go one step back, and look at the references in the paper you've cited in order to find more information.

If this is surprising or confusing to you, go and read the first few paragraphs of any research paper. Look at the references that are included there. They will be richer, bigger sources of information. They will not be references to other small research papers that just say the same thing.

Formatting of references
Reference markers go after punctuation, and references are listed as endnotes, not footnotes. You will learn how to use references if you read research papers.

Use the following style, exactly as shown:



Chemdraw Settings
It really helps the group function if everyone uses the same Chemdraw settings so we can easily cut and paste figures. Use the Angewandte/Wiley settings. Pasting Chemdraw pictures into Word files is usually OK so long as you have checked all the antialiasing options in Chemdraw, otherwise convert to tiffs/PNGs (which often resize well).

Using colour in pictures can help to convey meaning clearly, but use it sparingly.

General Lab Practice
Compounds generated need to be stored in vials, rather than round bottom flasks, both to save space and free up glassware. You should write, in pencil (pen can easily become smudged by solvents) a small label for each compound which has on it the structure of the compound, its unique identifier, and then stick this on the vial. You should then weigh the vial with the label attached, but without a lid. This mass should be written on the label, so that the mass of material in the vial may easily be calculated at any time. An example label is shown below. Compounds should be transferred to these vials, which is simple for solids. For oils/liquids this may be achieved by dissolving the compound in a volatile solvent such as DCM, and evaporating the solvent under a stream of nitrogen, followed by subjecting the vial to vacuum in a desiccator.



Compounds will go ‘off’ if left at room temperature in light. By default you must keep everything in a fridge/freezer. Do not leave compounds out in your hood or on your bench. This also means you have to transfer compounds from RB flasks to vials, or else you will run out of space.

The area around balances should be kept clean.

Washing up of glassware should be done with hot water and soap, and acetone at the very least. Prompt washing up after use is vital for glass syringes to prevent them becoming blocked. Solvents (including acetone) should not be poured down the sink. Remember chlorinated solvents need special disposal.

If commercially available chemicals run low it is the responsibility of the last person who used them to reorder. For ordering chemicals, see the separate document on the use of the inventory. Need link here.

We will periodically have to borrow items from other groups. When we do this it is very important to return all these items, or replace any we have consumed. Typically if you use a small proportion of another group's sample (<5%) there is no need to replace, but a larger amount probably should be replaced - you need to clarify this with the person you borrow the chemical from. Some groups have log books of things that have been borrowed - make sure you sign those. Be courteous to other groups at all times. The lab is a communal space – do unto others as you would have them do unto you.

Literature and Internet Resources
The Chemical Literature: In addition to working in the lab, you need to read the chemical literature. This means identifying and reading papers of relevance to your project but also more generally to read papers of significance to the organic chemistry community. The central journals to look at are Nature, Science, Nature Chemistry, JACS and Angewandte, but you should also be checking JOC and Organic Letters, Chemical Communications and maybe Organic and Biomolecular Chemistry. These are all available online. Reading random papers is an excellent way to expand your knowledge of science. Many postdoctoral positions will require you to come up with your own proposals, and reading the literature is an excellent way of identifying your interests. If you notice papers of relevance to others in the group, you should bring those papers to their attention. Our Friendfeed room is an easy way to do this.

It’s very important for you to realize that your research project is your own, and that Mat is merely your advisor. Hence you must understand that you need to keep on top of the literature relevant to your project. You must tell Mat cool things about the literature, rather than the other way around.

Alerts and citation alerts: Sign up to receive email alerts of new issues of journals or check the ASAP pages of these journals regularly. This is easy to do on the journal websites. You can receive emails with embedded links to graphical abstracts of the articles, making it a lot easier to keep up to date.

The best way to stay alerted to the literature relevant to your project is to set up citation alerts in Web of Science. There will be some papers that are of particular importance to you/your project, e.g. reviews, or your own published papers. You will want to know if a new paper is published that cites those important papers. Web of Science has a feature that sends you an alert email whenever those key papers are cited. You’ll need to update this every now and again with new papers you want citation alerts for. Setting this up in Web of Science requires you to register for your own account (which we usually don’t need since we’re covered by the Library account). Setting up the alerts is then pretty self-explanatory (but a tutorial is needed here...). This is a very useful tool that many academics don’t even know about.

Keeping on top of references: Note - the following instructions are on hold since as of August 2010 Connotea is being very slow... Group members are recommended to look into Mendeley Our Connotea group is Todd-lab. When you join the group, sign up for Connotea and let me have your user name so I can add you to the group. Connotea is an excellent way of generating a library of papers relevant to the group’s research interest, and you are strongly encouraged to post items to it. It allows you to tag papers with words you find intuitive, and this is a big advantage over having a stack of paper copies of articles.

It is quite easy to order Inter-library Loans (ILL’s) through the library website for more obscure papers and patents, but this may cost money, so please make sure the paper is necessary before you do this, or that ordering the paper is free. The chemistry librarians are very helpful and friendly if you have technical issues.

Other resources: Use Google and Wikipedia frequently but with no-brainer precautions. The web is becoming increasingly useful as a collaborative portal. Our group is involved in the Synaptic Leap. You're all encouraged to read other PhD students’ blogs, listed over on the links page.

As scientists, we’re faced with a large amount of community data we need to keep on top of: papers, websites, news articles, blog posts etc. We should be making the most of the tools at our disposal to manage all these data.

Create an account on Friendfeed, and follow my page as well as signing up to the todd lab room. Friendfeed allows us to share pages, ideas, blog articles, etc that are work-related (only – if you want to share non-science things, use twitter or something...). You’ll find you can learn a huge amount from others using this tool. Sharing items with the bookmarklet is very easy.

Some people view web tools/blogs as a distraction from doing science, and this is certainly true when taken to extremes. However, sharing data over a large network of people is very efficient when done online, and you should find these resources help you streamline managing data and finding people doing work that is relevant and interesting to you. These tools effectively allow us to collaborate with much larger numbers of people than we can if we just rely on verbal/email communication.

Group Meetings
You must attend the Thursday Morning Problem Sessions at 10 a.m. during semester. You should take an active part in these sessions, which means asking questions about anything you don't understand.

You should also attend all organic seminars – a very important part of your education that will broaden your knowledge and may be randomly useful to your project.

Group meetings are on Mondays at 1. There is a separate page for this.

When you're done
Through the heartache of coming to the end of your research stay, there are some things you need to do before you leave the group


 * Your lab books need to be complete and up to date
 * Spectra must be labelled and filed. If you possess any unnecessary/redundant spectra, throw them out
 * All electronic data files that are important must be labelled with a filename that allows them to be identified as yours, and with the relevant page in your lab book. Any data you are keeping must be backed up
 * Any remaining good chemical samples: ensure that the relevant vials are labelled clearly, then placed in a Tupperware box with your name on it. Any indeterminate brown junk - dispose of.
 * No RB flasks or NMR tubes are to be left with samples in them. No cardboard or paper in the fridge/freezer.
 * Give all lab notebooks and folders of spectra to Mat. Don't give him anything else, such as mascots, pencils, or lucky TLC spotters
 * Clear your bench and hood area so that the next person to come along can find what they need
 * Any commercial chemicals you recently bought need to be uploaded to the inventory, and any bottles recently used up need to be deleted from the inventory. If you were storing reagents in your bench space, now is the time to relocate them back to the area they ought to be in.
 * Clean up your hood and bench area.
 * Dispose of any paper or other junk on the shelves near your desk