Building Organic Molecules with Functional Groups

This tutorial demonstrates how to rapidly build organic molecules using the Template Tool’s functional group library and keyboard shortcuts. Rather than drawing every atom, you can attach complete functional groups to a molecular scaffold with a few keystrokes.

Activate the Template Tool with Ctrl+3 or by clicking its icon in the toolbar, then select the Groups tab.

Part 1: Building a Substituted Aromatic

Let’s build 4-nitrotoluene by starting with benzene and adding functional groups.

Start with benzene

Use Build → Insert → Molecule… and search for “benzene”, or draw a benzene ring with the Draw Tool.

Switch to the Template Tool

Press Ctrl+3 and navigate to the Groups tab (press → twice or click the tab).

Add a methyl group

Type c to select methyl. Click on any hydrogen on the benzene ring to replace it with -CH₃.

Add a nitro group

Type N (uppercase) to select nitro. Click on the hydrogen para to the methyl group (directly opposite) to create 4-nitrotoluene.

Optimize

Press Ctrl+Alt+O to clean up the geometry. You can also switch to the Auto Optimize tool.

Tip

Common aromatic substitution shortcuts:

• c — Methyl

• N — Nitro

• om — Methoxy

• F — Trifluoromethyl

• a — Phenyl (for biphenyl systems)

You can find other keyboard shortcuts for functional groups.

Part 2: Building Alkyl Chains Quickly

The Template Tool provides shortcuts for building alkyl chains without drawing each carbon. Let’s build a simple fatty acid: decanoic acid.

Start with a carboxylic acid

Draw a single carbon with the Draw Tool, or start with methane from Build → Insert → Molecule…

Add the carboxylic acid

In the Template Tool Groups tab, type C (uppercase) or co2 to select carboxylate. Click on a hydrogen to add the -COOH group. We now have acetic acid.

Build the alkyl chain

Now we’ll extend the chain. The shortcuts for n-alkyl groups are:

Shortcut	Chain Length
c or c1	Methyl (1 carbon)
c2	Ethyl (2 carbons)
c3	Propyl (3 carbons)
c4	Butyl (4 carbons)
c5	Pentyl (5 carbons)
c6	Hexyl (6 carbons)
c7	Heptyl (7 carbons)
c8	Octyl (8 carbons)
c9	Nonyl (9 carbons)
c0	Decyl (10 carbons)

For decanoic acid (10 carbons total including the carboxyl), type c8 to select octyl. Click on the hydrogen at the end of the carboxylic acid’s carbon to add an 8-carbon chain, giving you a 10-carbon fatty acid.

Tip

If you can’t see the entire molecule, you can go to View ⇒ Center to re-center the view.

Optimize

Run geometry optimization or use the Auto Optimize tool to get a reasonable chain conformation.

Note

Shortcuts are case-sensitive! Lowercase c followed by a number gives you n-alkyl chains, while uppercase C followed by a number gives you cycloalkyl groups.

Part 3: Branched and Cyclic Groups

Organic molecules often have branched or cyclic substituents. Here’s how to add them efficiently.

Branched Alkyl Groups

Build isopropylbenzene also known as “cumene” (a simple branched aromatic):

1. Start with benzene

2. Type I (uppercase) to select iso-propyl

3. Click on a hydrogen on the benzene ring

For tert-butyl groups, type K.

Cycloalkyl Groups

Build cyclohexylmethanol:

1. Start with methanol (draw or insert)

2. Type C6 (uppercase C) to select cyclohexane

3. Click on a hydrogen on the methyl group

The cycloalkyl shortcuts use uppercase C:

Shortcut	Ring Size
C3	Cyclopropane
C4	Cyclobutane
C5	Cyclopentane
C6	Cyclohexane
C7	Cycloheptane
C8	Cyclooctane

Part 4: Building a Drug-like Molecule

Let’s combine these techniques to build a more complex structure: a para-substituted benzoic acid derivative with multiple functional groups.

Target: 4-methoxy-3-nitrobenzoic acid

Build the scaffold

1. Insert benzene

2. Add carboxylic acid: Type C and click on a ring hydrogen (position 1)

3. Add nitro group: Type N and click on an adjacent hydrogen (position 3, ortho to CO₂H)

4. Add methoxy group: Type om and click on the para hydrogen (position 4, opposite CO₂H)

Optimize and verify

After optimization, verify you have the correct substitution pattern. The nitro and methoxy groups should be on adjacent carbons, with the carboxylic acid opposite the methoxy.

Part 5: Protecting Groups for Synthesis

The Template Tool includes common protecting groups used in organic synthesis.

Example: Building a Protected Amino Acid

1. Insert glycine using Build → Insert → Molecule…

2. Switch to the Template Tool Groups tab

3. Type fmoc to select the Fmoc protecting group

4. Click on one of the amine hydrogens

Available protecting group shortcuts:

Shortcut	Protecting Group	Common Use
boc	BOC (tert-butyloxycarbonyl)	Amine protection
cbz	Cbz (benzyloxycarbonyl)	Amine protection
fmoc	Fmoc (fluorenylmethoxycarbonyl)	Solid-phase peptide synthesis
tos or ts	Tosyl	Amine/alcohol activation
ms	Mesyl	Alcohol activation
tr	Trityl	Thiol/amine protection
troc	Troc	Amine protection

Summary: Functional Group Shortcuts

Quick Reference

Category	Examples
Alkyl chains	c, c2–c9, c0 (decyl)
Cycloalkyl	C3–C9, C0 (cyclodecane)
Branched	I (iso-propyl), K (tert-butyl)
Carbonyl	co (aldehyde), C (carboxyl), E (ester)
Nitrogen	N (nitro), cn (nitrile), n3 (azide)
Oxygen	om (methoxy), O (peroxide)
Sulfur	S (sulfonate), ms (mesyl), ts (tosyl)
Halogenated	F (CF₃), L (CCl₃), R (CBr₃)
Aromatic	a (phenyl), mes (mesityl)

Workflow Pattern

1. Draw or insert base structure

2. Activate Template Tool (Ctrl+3)

3. Go to Groups tab (→ twice)

4. Type shortcut for desired group

5. Click hydrogen to replace

6. Repeat for additional groups

7. Optimize geometry

See Also

• Template Tool Reference for the complete shortcut list

• Building with SMILES for an alternative rapid-building method

• Import by Name to import molecules by name over the network from PubChem

• Insert Fragments for inserting complete molecular fragments