Lecture Notes:

Lecture 2 Experimental Organic Synthesis

Searching Chemistry Journals/Databases

This lecture deals with literature searching and chemical database browsing (Reaxys
and SciFinder). Part of this lecture is covered by pages 411-418 in the course
textbook.

Scientific Journals
To a first approximation industrial (e.g. pharmaceutical and agrochemical) companies
produce/make/manufacture biologically active compounds, which they can sell. Their
results are typically published in patents and on a few occasions in scientific journals.
Universities, on the other hand, mainly produce/make/manufacture knowledge, which
is published and shared in scientific journals and in some instances in patents.
Most scientific journals are available to us through the State Library webpage
(www.statsbiblioteket.dk) or ordered from other European libraries.
Even within organic chemistry there are many scientific journals. As an example you
can find all sorts of research results regarding organic chemistry in Journal of
Organic Chemistry (J. Org. Chem.) and Organic Letters (Org. Lett.). Journals like
Carbohydrate Research (Carbohydr. Res.) and Bioorganic and Medicinal
Chemistry (Bioorg. Med. Chem.) are more specialised and exclusively contain
research results from the field of carbohydrate chemistry and medicinal chemistry,
respectively.
Other types of journals like Journal of the American Chemical Society (J. Am.
Chem. Soc.) and Chemistry, a European Journal (Chem. Eur. J) are broad journals
incorporating many types of research from different branches of chemistry (organic,
inorganic, biological, theoretical, physical, computational etc).

Scientific papers can be divided into several groups:

Reviews (oversigtsartikler): These are typically dozens of pages long and
comprehensively cover a certain research area (example: Reactions catalysed by
certain lanthanide salts). These types of papers do not contain any experimental
details but usually a long list of references to articles that do.

Full papers/full articles: These, usually thoroughly written pieces of science, give
detailed descriptions of the experimental results. Some journals like Tetrahedron
(Tetrahedron) and Organic and Biomolecular Chemistry (Org. Biomol. Chem.)
almost exclusive print full papers.

Letters/communications/notes: These give short accounts (2-3 pages) of scientific

results and typically do not contain experimental details. Some journals, however, do
make supplementary information containing full experimental detail available on the
internet.
Examples of journals that do not print full papers: Tetrahedron Letters (Tetrahedron
Lett.), Organic Letters (Org. Lett.), Angewandte Chemie (Angew. Chem. Int. Ed.),
Bioorganic Medicinal Chemistry Letters (Bioorg. Med. Chem. Lett.) and Chemical
Communications (Chem. Commun.).
Examples of journals that both print full papers and communications: Journal of the
American Chemical Society (J. Am. Chem. Soc.), Journal of Organic Chemistry
(J. Org. Chem.), and Carbohydrate Research (Carbohydr. Res.).

Patents: These are typically written in a legal language, which can make the
experimental protocol difficult to follow. Sometimes, however, very useful
experimental protocols can be obtained from the patent literature.

Writing references
It is important to know how to write the unique abbreviation associated with each
journal for literature referencing. You can choose different formats as shown on page
408, as long as you are consistent throughout your report.
Do not copy the reference given by Reaxys or SciFinder where, e.g. both volume
and issue number are mentioned. Only the volume (if that specific journal uses
volume numbers) should be mentioned for literature referencing, but without the
vol.. Some journals like e.g. Tetrahedron (Tetrahedron) will give you both an
issue- and volume number. The issue number should not be written in the reference. It
can be a good idea to consult a random article for inspiration as to which format
should be used for referencing.

Accessing journals
First example:
Lets say we want to read the following article (written in the style of the American
Chemical Society): White, J. D.; Hrnciar, P.; Stappenbeck; J. Org. Chem., 1997, 62,
5250-5251.
Our access to journals is provided through the State Library at Aarhus University, but
their webpage is in my opinion terrible. The best way is often to conduct at simple
google-search from a campus computer. So, type j. org. chem. or journal of organic
chemistry in google and go to the website of Journal of Organic Chemistry. This
will link to the front page of Journal of Organic Chemistry, which has the typical
appearance of a journal published by the American Chemical Society (ACS). Journals
like Journal of the American Chemical Society and Journal of Medicinal
Chemistry look similar since these are also ACS journals. From here, you can click
your way forward to the article you want to access by using the blue box. Select
Decade, Volume, and Issue and click GO. Scroll down and find the article we
were looking for.
The paper by J. D. White et al. is just two pages and it is characterised as a
communication. You can read the paper by clicking PDF or read the supplementary
information containing experimental details by clicking on the Supporting Info link
and then on the pdf-file.

Second example:
Lets this time look for the following paper: N. Wild, U. Groth, Eur. J. Org. Chem.
2003, 4445. Perform a google-search for european journal of organic chemistry and
go to the journal website. You will notice a different layout since this journal has a
different publisher (Wiley-VCH) than in the first example. You will also come across
this layout for the journals ChemMedChem, Chemistry, a European Journal and
Angewandte Chemie.
Click on All Issues in the left column and select 2003 to find your publication. The
rest should be easy. View the pdf-file and notice that it contains experimental details.
This is a full paper.

Third example:
Look for the following paper: Bozo, E; Vasella, A.; Helv. Chim. Acta, 1992, 75,
2613-2633. You will find that you run into problems since this journal is only
available on-line from 1998 with our current subscription. In this case you can find
the journal in the library on the 4th floor and photocopy the article you are interested
in. You must return the journal to the library as soon as possible (=immediately!) after
use.
For papers from journals not in the Chemistry Library or freely available from
Department computers, you can contact the librarian (Henrik Skadhauge Clausen) for
assistance.

Reaxys
The search engine Reaxys is probably the most powerful tool for searching organic
chemistry reactions by structure and physical data of organic compounds. Using
Reaxys it is also possible to do bibliographic searches for keywords and authors. To
conduct a search go to www.reaxys.com.

Simple reaction searches with specified structures

First example:
Go to the front page of the Reaxys-site. Notice that a search can be performed in
several categories e.g. Reactions, Substances, Literaure and so on. Start by
clicking on the first option Reactions. Then double click on the white frame to open
the drawing mode. Java is required for this to work. We will now search the primary
literature for an experimental protocol that describes how to convert a certain
molecule into another molecule.
Lets draw anisaldehyde (p-methoxybenzaldehyde) using the benzene template and
the single bond-option in the upright menu on the left. Now mark (select) the structure
by the box-option in the top of the upright menu. Copy and paste the structure and
change one of the structures to the product you would get by addition of MeMgI to
the aldehyde function. Choose the reaction arrow in the upright menu and place this
between the reactant the product. You are now ready to conduct a literature search so
click on Transfer Query and next the Search Reactions button. A hit set of 34

reactions is then displayed but notice that some are duplicates. It is often possible to
link directly to the journal web-site.

Second example:
If you needed the secondary alcohol produced in the example mentioned above you
would probably have used your chemistry intuition to plan to go via anisaldehyde. If
anisaldehyde, however, is not available to you as a starting material, you will need to
prepare this too. If it is not obvious to you how to prepare anisaldehyde you can
simply draw it as the only substance. So, go back to the drawing mode (click Query
in upper left corner and then EDIT) and erase the reaction arrow and product. Click
Transfer Query which will take you back to the Reaxys start page with now only
anisaldehyde displayed in the window. If you now click Search Reactions you will
get all the records of reactions in which anisaldehyde is either a main or side product.
This is quite a few. You can slightly narrow down your hit set by choosing the
Document type option in the left menu selecting journal. Then, only references
from scientific journals and not patents or books are displayed. The latter two can
from time to time be difficult to time to get a hold of.
The menu on the left can be used to further narrow down a large hit set to only be
displaying e.g. reactions over one step (No. of steps) or the highest yielding reactions.

Third example:
Draw 1,2,4,5-tetra-hydroxycyclohexane and click Transfer Query and Search
Reactions to find records describing this as the product of a chemical reaction. You
will notice that this provides you with a hit set containing different stereoisomers of
tetrahydrocyclohexanol.
Lets say that we were only interested in one isomeric product and not reactions
exclusively forming an undesired diastereoisomer. To only display hits having e.g. an
all-cis relationship between hydroxyl substituents go back to the drawing mode by
clicking Query in the top left corner and then double click in the drawing frame.
You can now alter the chemical structure by e.g. changing the straight bonds for
wedged bond of your choice (up or down). Click Transfer query and re-conduct
the previous search. You will notice you now have a smaller hit set.

Example four:
Draw the compound N-acetyl glycine and its phenyl ester in the drawing mode (an
acetyl group is the MeC=O from acetic acid). Say we want to find procedures that use
the N-acetyl -amino acids as the starting material (this can be glycine, alanine,
phenylalanine, tyrosine, etc) and form the corresponding phenyl ester. Lets for this
exercise assume that we are interested in any para-substituted phenyl ester of any
-aminoacid. It is a reasonable assumption that the chemistry to make a phenyl ester
is similar to that of making a para-substituted phenyl ester.
What this means for the search is that we can have any substituent on the -carbon
and any substituent in the para-position of the phenyl group. Luckily it is possible to
make Reaxys understand that we are open-minded about certain positions in a
molecule.
In the drawing mode place an -substituent on both the reactant and product and in
the para-position of the product. Now choose the book with an R on the cover from
the top menu. This will open a box from where you can pick different open
substituents. X means any halogen atom and M is any metal. G* means any
substituent/atom except hydrogen, while GH* is any substituent including hydrogen.
For this search choose GH* and place this as the and para-substituents. Click
Transfer query and conduct the search. All the hits seem to use some kind of
carbodiimide coupling reagent. Say I want to narrow down the hit set to only contain
reference protocols that use my favourite coupling reagent: EDC. For this click
Reagent/catalyst

in

the

left

menu

and

choose

1-ethyl-(-3-(3-

dimethylamino)propyl)-carbodiimide. The new hit set should now only contain

examples where EDC has been used as a reagent.

Example five:
Reaxys is also a powerful tool for quickly obtaining physical and spectroscopic data
for known compounds. For this exercise change the default Reactions option for
Substances. Then, double click on the empty window frame to take you to the
drawing platform and draw N-benzyl aniline. Click Transfer query to go back to the
Reaxys page and perform the search. In the drop down menu on the left you can
choose the data you are after (melting point, boiling point, optical rotation,
spectroscopic data etc.). Click Spectroscopic data, and NMR spectroscopic data to

get a list of publications that list NMR spectral values for this compound. Notice that
data is also available for e.g. the hydrobromic and hydrochloric salts etc.).

SciFinder
The SciFinder search engine has like Reaxys numerous functions. For you to use
SciFinder you must first sign up, which only can be done with a Department of
Chemistry e-mail address (xyz@chem.au.dk or student-number@stud.au.dk). Make
sure you do this. You should all have a stud.au.dk address that receives e-mails in the
same inbox as your post.au.dk email.
Since these lecture notes are only meant to give an introduction to literature searching,
a comprehensive coverage should not be expected.
Some of the powerful tools that can be used with SciFinder are listed below:

i)

Searching for words/phrases in article abstracts (resum).

ii)

Searching for publications by a given author.

iii)

Searching for articles that cite/reference a certain paper.

iv)

Specific structure searches or searches based on CAS numbers.

v)

Searching for commercially available compounds.

Example 1:
First, it is necessary to login to SciFinder at https://scifinder.cas.org using a login
and a password. If you get in, click Accept to accept the licence agreements before
you will be able to search the literature. This first example demonstrates how to
search for articles covering a certain subject e.g. how to oxidise sulphides (sulphur
ethers) to sulfoxides. Notice that Research Topic has been selected by default. In the
blank search field one can now fill in keywords that would be expected to be present
in the article abstract. As a suggestion write the words: sulfide (American spelling of
British English sulphide both words can be used interchangeably) oxidation,
sulfoxide, and mild and click Search. Tick the top box and click Get
References to see a list of papers with the four words in the abstract or title. Since
SciFinder both searches its own database and Medline some hits may be present
twice. These can be removed by choosing the Tools-option and then clicking
Remove Duplicates. It is furthermore possible to pick out the papers from the list

written in English and not e.g. Chinese or French by clicking Refine and then
choose Language and by clicking English and Refine. Since SciFinder also
includes abstracts from conferences and patents we might want to further cut down on
the size of the hit set before we start choosing which papers to actually read. Click
Document Type under the Refine option and select Journal, Letter, and
Review before clicking Refine.
It is possible to read the abstract of the papers by clicking on the paper title. Clicking
the Full Text option will in many cases link you directly to the paper.
Among the references in the hit set is a paper from J. Org. Chem. To quickly locate
this paper without looking through the whole list is to click Analyze option in the
right hand side of the page. Then choose Analyze by: and Journal Name, then
Show More and Sort by Natural order. Scroll down to select Journal of Organic
Chemistry and click Apply. You can now read the abstract of this paper or access
the whole publication as mentioned before.
Notice the option Get Related Citations and choose Citing. Selecting this option
displays a list of papers citing this particular J. Org. Chem. paper. A large number of
citations suggest that an article is an important piece of scientific work and that it has
been used by many other scientists. This particular paper has been cited more than 90
times, which is a quite high number.

Example 2:
This example demonstrates how to search using chemical structures. To start a new
search click on the SciFinder symbol in the upper left corner of the page.
Now, under Substances click Chemical structure and click inside the frame that
opens to be taken to a drawing program. Here, sketch N-tertbutoxycarbonyl pyrrol
(pyrrol is a five membered unsaturated ring with a nitrogen atom) and click OK and
then Search. By clicking the conical flask icon a list of commercial suppliers will
be displayed. If the aim is to prepare the product yourself, go back and instead choose
Get References and then Limit results to: Preparation and click Get. A list of
papers describing the synthesis of Boc-pyrrol is now displayed. This can be narrowed
down by selecting the Analyze or Refine as described previously.

Example 3:
Click on the SciFinder symbol in the upper left corner to start a new session.
Each compound ever made or reported in the literature is given a unique CAS
Number (Chemical Abstract Service Number). These can be used to easily locate
chemical compounds and chemical catalogues is a good place to search for them. If
you wish to find a procedure for making e.g. -D-glucosepentaacetate (CAS Number:
604-69-3) choose Substance Identifier under Substances and then write the CAS
Number of the substance you wish to search for and click Search. Again you can
find commercial sources or search for ways of preparing the substance by selecting
Get Commercial Sources or Get References as discussed before.

Example 4:
If you are interested in searching in the publication record of a specific scientist this is
also possible using SciFinder. On the front page choose Author Name. As a
suggestion you can write Skrydstrup in the Last name box and T in the First
box. Then click Search and tick the boxes with the name or names you accept as
hits. Click Get References and then Remove Duplicates to see the full publication
record of Professor Troels Skrydstrup from our Department.

Exercises
(Answers are given on the last page)

Exercise A:
Find a review about synthesis of complex carbohydrates written within the last twenty
years by an author named Wong.

Exercise B:
Is 1,4-dimethoxybenzene commercially available? Can it be purchased from Aldrich?
What is its CAS number?

Exercise C:
Find a recent protocol for the following reaction where the main product is the
primary alcohol. Are there examples of reactions where the primary alcohol is the
minor product?: (Hint: Use Reaxys and be aware that the program doesnt
understand chair conformations)

Exercise D:
Find a list of procedures for converting a general carboxylic acid into its pyrrolidine
amide (Hint: Use G* on chosen atoms). This will give you more than 3700 hits.
Some of these hits have the pyrrolidine amide already present in the reactant. To
avoid this you can insist on a certain atom e.g. the carbonyl carbon of the reactant is
the carbonyl carbon of the amide product. To do this, go back to the drawing mode
and select the icon below the reaction arrow and choose Manual atom map. Now
click on the carbonyl of the reactant and drag an arrow to the carbonyl atom of the
product. The number 1 will then appear on both reactant and product signifying that
these atoms are the same. Now perform the search again and notice that all hits now
are reactions on the carbonyl functionality.
O
HN
pyrrolidine

N
a pyrrolidine amide

Exercise E:
What is the melting point of 2,4,6-trinitrotoluene when recrystallised from methanol?
In which journal was this reported?

Answers to Exercises
Answer A: Koeller, K. M.; Wong, C.-H. Chem. Rev. 2000, 100, 4465-4493.

Answer B: Yes, 1,4-dimethoxybenzene is commercially available from Aldrich. CAS:

150-78-7.

Answer C: Wang, C.-C.; Luo, S.-Y.; Shie, C.-R.; Hung, S.-C., Org. Lett. 2002, 4, 847850. Das, S.; Sanjoy, K.; Mallet, J.-M.; Sina, P., Angew. Chem. 1997, 109, 513-516.
Hernandez-Torres, J. M.; Anchkar, J.; Wei, A., J. Org. Chem. 2004, 7206-7211.
Article that reports primary alcohol as minor product: Garegg, P. J.; Hultberg, H.;
Wallin, S., Carbohydr. Res. 1982, 108, 97-102.

Answer D:

Answer E: Melting point: 43-44 C, Reported in Polish Journal of Chemistry, 1984.