Project ChEMU
Guidelines for Annotating Chemical Entities
related to Chemical Reactions
Version <1.02.1>
Revision History
Version Number,

Revision made by

Change Summary

ChristiancreatedDate

1.00

1.01

1.02.1

Druckenbrodt
Christianadjusted

Druckenbrodt
Christianadjusted

Druckenbrodt

Contents
SCOPE OF THE GUIDELINE................................................................................................................................................... 3
OVERVIEW ........................................................................................................................................................................... 3
INTRODUCTION TO PATENTS .............................................................................................................................................. 4
HIGH LEVEL RULES............................................................................................................................................................... 4
Part 1: Entity Annotation ........................................................................................................................................................ 5
EXAMPLE_LABEL ............................................................................................................................................................. 5
REACTION_PRODUCT ...................................................................................................................................................... 5
STARTING_MATERIAL...................................................................................................................................................... 5
REAGENT_CATALYST ....................................................................................................................................................... 6
SOLVENT.......................................................................................................................................................................... 6
TIME ................................................................................................................................................................................ 6
TEMPERATURE ................................................................................................................................................................ 7
YIELD_PERCENT ............................................................................................................................................................... 7
YIELD_OTHER .................................................................................................................................................................. 7OTHER_COMPOUND ....................................................................................................................................................... 71

Real Live Problematic Examples.......................................................................................................................................... 8Missing tags..................................................................................................................................................................... 8Wrong tags - that must be changed................................................................................................................................ 9Wrong tags - that must be deleted ............................................................................................................................... 112

SCOPE OF THE GUIDELINEThis document is the manual for the Full-Text Patent Annotation (FTPA) project and should advise how
to annotate manually (or check pre-annotated) parts of a chemical reaction, e.g. chemical entities,
reaction conditions etc. in patents correctly. It will provide definitions in which cases and how a stringof characters embedded in text of patents must be annotated accordingly. The resulting manuallyannotated BRAT files can be used as a so-called “gold standard” in order to determine Recall andPrecision values regarding corresponding automatic annotations, produced by state-of-the-art text
mining tools.

OVERVIEW
The recognition of chemical reactions is an essential step in the extraction of chemical information fromany kind of document. This goes beyond the annotation of chemical entities as it also covers their role
within the context of a chemical reaction. In addition, some typical conditions should be annotated which
provide contextual hints to the presence of a chemical reaction, whilst also providing additional
information beyond a simple starting material/product relationship. In the current FTPA project we only
focus on representations of entities and conditions as strings in snippets of running text. Drawn
chemical entities/structures and conditions in pictures, schemes or tables are excluded, as state-ofthe-art technologies are currently not able to reach enough quality in such regions of documents.
Determination of acceptability for chemical entity strings in a reaction derived from snippets of runningtext is often quite difficult. The complexity originates from the matter of fact, that chemical entities
present in a reaction snippet may or not may not play a certain role in a reaction. The problem here isto identify all chemical entities playing a role in the reaction in the first place followed by the classificationof these chemical entities according to the role they have in the chemical reaction.
An additional problematic issue is that strings used in snippets often refer to context beyond theindividual snippet. The string used in the snippet may only be a representative of the complete chemicalentity. Strings of chemical entities themselves can be detected, annotated, and to some extend resolved
by state-of-the-art name-to-structure tools. Representatives, be it a label or a reference to the “productof a certain reaction”, can be detected and annotated within this context but they cannot be resolved
without any coreference.
As the basically only snippets of reaction texts will be part of the to be annotated text one further issue
is not so prominent but is still present: in context/within natural language may change their intrinsic
meaning depending on the different environments. That means, from an atomistic point of view, a3

string/word/term/group of characters may have an intrinsic unique meaning in the chemical domain(e.g. “Glucose”; “gold”), but embedded in running text it might mean something different (e.g. “Glucosetransporters are a wide group of membrane proteins”) although it is still the same domain or even inother domain (“The exchange rate under the gold standard monetary system…”). As a consequence,
documents, frequently annotated automatically by machines, will contain a huge amount of strings
annotated as chemical entities. Although all of these annotations are somehow related to chemistry,
only a certain amount of them are actually contextual chemical entities. Due to the above explained
contextual constraints, the embedded meaning for the rest of the annotated strings in running text is
not a chemical entity but something else.

INTRODUCTION TO PATENTS
A patent is a right granted to the owner of an invention that prevents others from making, using,importing or selling the invention without his permission. A patentable invention can be a product or aprocess that gives a new technical solution to a problem. It can also be a new method of doing things,
the composition of a new product, or a technical improvement on how certain objects work. For an
invention to be patentable, it must, in general, satisfy three key criteria: New, inventive step, andindustrial application.
The sections of patents are quite conserved: title, bibliographic information (patent number, dates,inventors, assignees, IPC classes, …), abstract, description, and claims. Most of the chemical data will
be found in the experimental section of the description, while compounds claimed (protected) areavailable in the claims section. Drawings, sequences, or other additional information will normally befound at the very end of a patent.
This particular project concentrates exclusively on the experimental section in the description as thesource of reaction text snippets.

HIGH LEVEL RULES
In general, chemical reaction is a process leading to the transformation of one set of chemical
substances to another. Here, the task is to identify specific types of chemical compounds, i.e. to assign
the label of a chemical compound according to the role the chemical compound plays within a chemicalreaction. Mostly the reaction full text can be divided into actual reaction and the following work-up – inthe reaction the product is completely formed. In the work-up the product remains unchanged and steps
undergone are for isolation of the product only. The actual reaction and the following workup must be
kept separate in the annotation. The presence of a chemical entity in one of the separate parts hasconsequences for the annotation.
4All snippets represent reaction full texts and are already pre-tagged. All tags must be revised and – ifnecessary – corrected. Missing tags must be set. Entities present more than once – also in different
representations – must be annotated at each occurrence.

Part 1: Entity Annotation
We define 10 different entity types, including:
EXAMPLE_LABEL, REACTION_PRODUCT, STARTING_MATERIAL, REAGENT_CATALYST,SOLVENT, TIME, TEMPERATURE, YIELD_PERCENT, YIELD_OTHER and OTHER_COMPOUND.

EXAMPLE_LABEL

If a reaction label is given in the snippet this must be annotated with this tag.
Words like “Example”, “Step”, “Intermediate”, “Core” and “Reference example” must not beannotated, neither are parentheses, brackets or braces. Do not confuse reaction labels andcompound labels. This tag must only be annotated to reaction labels.

There can be more than one reaction label in a snippet as reaction labels consider both the label ofthe finally generated product, as well as, the described intermediate product.
REACTION_PRODUCT, orA product is a substance that is formed during a chemical reaction and must be annotated with thistag.
As REACTION_PRODUCT all representations of the product must be annotated, product nameand/or label but also representatives like “title compound” generally pointing to the title of thereaction snippet. All such variants of the reaction product must be annotated in the snippet.
STARTING_MATERIAL, or5

A substance that is consumed in the course of an organic chemical reaction providing carbon atoms
to products is considered as starting material and must be annotated with this tag. In inorganic
reactions the prerequisite is that the starting material provides any atoms to the product.
REAGENT_CATALYST, orA reagent is a compound added to a system to cause or help with a chemical reaction. Compounds
like catalysts, bases to remove protons or acids to add protons must be annotated with this tag. Inorganic reactions compounds providing non carbon atoms to a product are also considered
REAGENT_CATALYST.
Reagents must be involved in the reaction. Compounds given in the course of work-up, like MgSO4
for drying must not be annotated with this tag. These must be annotated as OTHER_COMPOUND.
It may well be that within the same snippet compounds may have a role as REAGENT_CATALYSTand OTHER_COMPOUND.
SOLVENT

A solvent is a chemical entity that dissolves a solute resulting in a solution. The solvents used in thereaction must be annotated with this tag. In case of solvent mixtures all individual solvents must beannotated. Solvents that also have the role as STARTING_MATERIAL must only be annotated assuch. Solvents used in the work-up must not be annotated as SOLVENT but as
OTHER_COMPOUND.

It may well be that within the same snippet compounds may have a role as SOLVENT andOTHER_COMPOUND.
Alternatively used solvents must not be annotated (e.g. in case of ‘dichloromethane or chloroform
was used’ none of the mentioned solvents must be annotated).
TIME

The reaction time of the reaction must be annotated with this tag.

6

If just one particular time information is given (e.g. 20 min, 2 h or 3 d), that time information must beannotated.
If different procedures with different reaction times were carried out
consecutively (e.g. 30 min stirring at 20 °C, then 2 h reflux) the individual
times must be annotated.

TEMPERATURE, orThe temperature (range) at which the reaction was carried out must be annotated with this tag.
In case a reaction was carried out at more than one temperature, the given lowest and the given
highest temperature must be annotated. Temperatures within this range must not be annotated.
The temperature range can be given with (1) numerical values or (2) by a specific keyword. “roomtemperature (RT)”. This keyword must be annotated if the temperature is not specified by a concretevalue. “Room temperature” is representing 20 °C here. This must be considered when setting
ranges and entering only the minimum and maximum temperature.
It must be kept in minds that the xml expression for °C is given as “&#176;”.
YIELD_PERCENT

Yield given in percent values must be annotated with this tag. Only isolated yields must be annotatedwith this particular tag.
YIELD_OTHER, orYields provided in other units than % must be annotated with this tag. YIELD_OTHER can be given
as amount of substance (in mol or mmol) received mass of substance (in g or mg)
OTHER_COMPOUND, or

Other chemical compounds, which are not the products, starting materials, reagents and solvents,
must be annotated with this tag. This can be standard chemicals used for drying but also the overall
title compound of a set of reactions present in the snippet.
7

The following colors are used to distinguish different entity types in BRAT.

Real Live Problematic Examples
All the above entities are generally pre-tagged either by correlation with Reaxys content or by achemical entity recognition process. Some mistakes are intrinsically present in the underlying
processes. Therefore, the main aspect of the chemical entity annotation will be a thorough check ofexisting tags. Greatest care must be taken to ensure consistency and correctness.
In general, three aspects have to be considered here:•••

Missing tags – that must be annotatedWrong tags – that must be changed
Wrong tags - that must be deleted

Missing tags

The solvent DMF – dimethylformamide is missing in the original annotation. The mapping process, aswell as, the chemical entity recognition are mostly depending on systematic names. Abbreviations likeDMF here may cause problems and remain un-tagged.

8

The solvent water is “hidden” in this specific term. It is not detected by chemical entity recognition.

The term “aqueous” can be ambiguous. Only in cases where this word is used as a placeholder forthe compound annotation must be done. In the above case the “aqueous” is only further identifying
the layer and must therefore not be annotated.

The absolute yield provided in mmol is not pre-annotated. Please add further annotation
YIELD_OTHER.

The second label provided for the product is missing and must be annotated. In addition, the absolute
yield in mmol is missing.
In case the reaction is missing the starting material and shows only the REACTION_PRODUCT as
indirect entry the STARTING_MATERIAL should be identified semantically.

Here no STARTING_MATERIAL was pre-tagged. By semantic analysis of the snippet 56f can beidentified as STARTING_MATERIAL.

Wrong tags - that must be changed

9Dichloromethane is present in two instances. Whilst the first instance is correctly tagged as
SOLVENT the second instance is clearly part of the workup (washed with…) and must therefore beannotated as OTHER_COMPOUND.

3-chloro-N-propyl aniline has been tagged as OTHER_COMPOUND but must have been annotatedas REACTION_PRODUCT

1-benzhydryl-3-methyl-5-(2-methyl-pyridin-3-yl)-1H-pyrimidine-2,4-dione has been tagged as
REACTION_PRODUCT but must have been annotated as STARTING_MATERIALNotes:•In case the reaction in the snippet holds annotations for main STARTING_MATERIAL and
REACTION_PRODUCT which are not directly given no changes regarding assignment of thechemical entities must be made within the reaction regarding REAGENT_CATALYST,SOLVENT and further STARTING_MATERIALS. These entities are pre-tagged by match withdata excerpted for Reaxys. Without any context present there practically no chance to clearup matters.

Methanol is also a typical SOLVENT but according to pre-tagging it is a REAGENT_CATALYST. No
changes can be made here.
•If either STARTING_MATERIAL or REACTION_PRODUCT is given directly necessarychanges must be made. These changes are often necessary when the reaction used for pre10

tagging was an “analogue reaction”. As for these no starting materials are entered by default
starting materials are tagged by the chemical entity recognition only as
OTHER_COMPOUND.

Intermediate 3 has not been detected at all and 3,3-difluorocyclobutanamine hydrochloride only as
OTHER_COMPOUND. Both must have been tagged as STARTING_MATERIALS

Wrong tags - that must be deleted

40&#176;C was tagged as TEMPERATURE. In this case a range is given with the lowest
temperature at 20 °C (room temperature) the highest point with 75 °C. Therefore, the tag for40&#176;C must be deleted.

Cotton is no chemical compound. This wrongly assigned tag must be deleted.

11