The Aldol Reaction as Search Sample with WebReactions

The WebReactions program is largely self-explanatory and detailed instructions should not be necessary. Green messages at the bottom of the screen act as a guide through the search process. For illustration, however, the four steps in the procedure are followed through here for a simple aldol reaction as the query.


1. Defining the Query Reaction

First select Define Reactant at the top of the screen and draw the reactant(s) for the query reaction as shown below at the left. All carbons which change must be drawn, both here and in the product.

When Define Product is now selected, the initial reactant drawing reappears. It must be altered to become the product(s) by fixing the bonds that change, as at right. Clicking any bond changes its order. This automatically affords the necessary mapping for the program to know which reactant atoms become which product atoms.


2. Running the Query Reaction

When Search Database is now selected the whole reaction appears on the screen. Typically WebReactions can keep track of the atom-to-atom correspondence between reactant and product sides. However, sometimes this mapping information cannot be deduced from the way the reaction was drawn. In these cases the program asks you to complete the mapping by highlighting unmapped atoms of the reactant (left picture below). Then you need to click on the corresponding atom on the pruduct side. If there is no such atom then press the button "This atom has no counterpart".

Once the reaction is completely mapped some atoms appear in red or blue color and the number of initial database hits is shown (right picture below). Atoms shown in red are reaction centers, while blue atoms indicate unchanging groups. Also a new choice bar appears at the top for the subsequent steps, and a slide bar appears as well to define the minimum yield acceptable in the matching entries.


3. Customizing Hit Conditions

The number of hits registered has been selected by an automatic pruning process which initially refines the matching of hits to query so as to display a reasonable number of hits to manipulate. If the number is too large or small or if the automatic selection of query features need customization, select the tab Fine-tune Hitlist. With the cursor on any colored atom, clicking will bring up a list of detailed choices of matching features for that atom or group. The next illustration shows the choice for the red carbon of acetone.

These choices, of inter/intramolecular, substitution, etc., on the red atom, are to match the nature of that atom as drawn in the query. For example, when "match no of attached carbons" is checked here, each matching reaction must have a primary carbon in this position, as it is in the query drawing. The matching features in the window may be altered with the mouse. As these choices for the desired extent of similarity or matching are made, the number of matched entries changes accordingly. In a similar way the popup menu at the bottom of the window offers a choice for refining the nature of the atom or group which is lost from this carbon in the reaction.

Fine-tuning the other construction atom is shown next, below, and displays a similar window of the degree of matching. In this case, the original 33 hits were displayed, but then the boxes for attached hetero atoms and for stabilization (i.e., adjacent electron-withdrawing group) were deselected, and so the number of hits rose to 71.

The blue atoms represent functionality which is unchanged in the reaction. These may similarly be defined more or less closely with a choice window, as shown below for the unchanged carbonyl. The number of hits displayed will reflect the extent of refinement or similarity defined in the choice window. As the choice is made more specific, the number of hits generally decreases.

The yield bar at top center allows one to set the minimum acceptable yield for precedents in the hitlist. As the slider is moved the corresponding number of hits remaining is instantly displayed. However, a significant number of database entries quote no yield. These are indexed at 0% and so the number of hits may often increase sharply at the 0% position on the yield bar, and indeed may contain some good reactions without yields recorded in the database.


4. Browsing Database Reactions

Now the query is set and its level of detail has been refined in the several Fine-tune windows. To view the entries on the hitlist, select Browse Hits and use the buttons at the bottom to browse among the database entries which match.

A typical hit is displayed below with the two reaction center carbons in margenta matching the aldol reaction query.

The textual information for the current entry is retrieved by selecting the Reaction Text tab at the top and scrolling through the literature reference and reaction conditions which are available from the database. The Display Molecules tab allows for a separate, larger view of each molecule involved in the current reaction entry. The tab Select Databases at the top right will display the choice of databases being accessed.