(R)-(+)-2-Methyl-2-propanesulfinamide (CAS 196929-78-9, C4H11NOS, MW 121.20) – commonly known as Ellman’s sulfinamide – is one of the most widely used chiral auxiliaries in asymmetric synthesis. It converts aldehydes and ketones into N-sulfinyl imines that undergo highly diastereoselective addition, giving enantiopure chiral amines after cleavage. This guide covers its chemistry, use and specifications.
1. What Is Ellman’s Sulfinamide?
The molecule is tert-butanesulfinamide carrying the sulfinyl (S=O) group with (R) configuration. The bulky tert-butyl group and the chiral sulfur centre together control face selectivity when the sulfinyl imine is attacked by nucleophiles – the basis of the widely used Ellman asymmetric amine synthesis.
2. Chemistry and Properties
| Property | Value |
|---|---|
| Molecular formula | C4H11NOS |
| Molecular weight | 121.20 g/mol |
| Appearance | White to off-white crystals |
| Purity (HPLC) | 99.0% min |
| Chiral purity (LC) | 99.0% min |
| Solubility | Soluble in common organic solvents (DCM, THF, toluene); limited in water |
| Stability | Moisture and oxygen sensitive; store cold and dry under inert gas |
3. How It Works: The Ellman Method
- Condensation: sulfinamide reacts with an aldehyde or ketone (with a dehydrating agent) to form the N-tert-butanesulfinyl imine.
- Diastereoselective addition: organometallic reagents (Grignard, organolithium, Reformatsky, allylations) add to the imine with high face selectivity controlled by the sulfinyl group.
- Cleavage: mild acid removes the sulfinyl group to release the enantiopure amine (as its salt), recovering the sulfinamide auxiliary concept.
The (R) and (S) forms of the sulfinamide give access to opposite amine configurations – making the pair a complete toolkit for chiral amine synthesis.
4. Specifications
Standard grade: white to off-white crystals; HPLC purity 99.0% min; chiral purity (LC) 99.0% min. For asymmetric work the enantiomeric purity is the critical specification, because any (S) impurity translates directly into reduced stereoselectivity in the final product.
5. Applications Overview
- Pharmaceutical synthesis – enantiopure amines and amine-containing APIs (chiral building blocks).
- Agrochemical and specialty chemistry – chiral amine intermediates.
- Ligand/catalyst synthesis – chiral amine ligands for asymmetric catalysis.
- Custom synthesis – scaled manufacture of chiral amines from ketones/aldehydes.
6. Application Notes
6.1 Chiral amine building blocks
Typical targets include chiral amines used in antiviral, CNS and cardiovascular drugs, where a single enantiomer determines activity. The sulfinyl route is valued for its predictability and the crystalline, easily handled intermediates it forms.
6.2 Practical handling
Use anhydrous solvents and inert atmosphere; the free sulfinamide hydrolyses/oxidizes slowly on exposure. Store cold, sealed and dry.
7. Choosing (R) or (S)
The choice depends on the target amine’s absolute configuration. The (R) sulfinamide generally leads to (R)-amines through the standard addition/cleavage sequence, though the sense of induction must be verified for each substrate. Both enantiomers should be qualified for a robust route.
8. Buying Guide
- Specify HPLC purity (≥99.0%) and chiral purity (≥99.0% by chiral LC).
- Request chiral chromatography data (e.g. enantiomer ratio) on the COA.
- Confirm packaging under inert atmosphere, cold storage and shelf life.
- For scale-up, confirm batch-to-batch consistency of the enantiomeric ratio.
9. Safety and Handling
- Irritant; avoid inhalation and skin contact, use gloves/goggles and ventilation.
- Moisture-sensitive solid – keep containers closed and dry.
- Dispose per local regulations; request MSDS from supplier.
10. FAQ
What is Ellman’s sulfinamide used for?
As a chiral auxiliary to make enantiopure amines from aldehydes and ketones via N-sulfinyl imines.
Can you supply the (S) enantiomer too?
Custom synthesis of the (S) form (CAS 343338-28-3) and gram-to-kilogram quantities are available – contact us.
11. References and Further Reading
- PubChem entry for 2-methyl-2-propanesulfinamide (CID via PubChem REST API).
- Supplier COA and MSDS for the specific grade quoted.
- Literature on N-tert-butanesulfinyl imines in asymmetric amine synthesis.
This article is published for industrial and technical reference by PolyblueChem. Verify all values against the supplier’s COA and applicable standards before specification.
PolyblueChem supplies (R)-(+)-2-methyl-2-propanesulfinamide (CAS 196929-78-9) with COA and MSDS. Contact us for specifications and quotations.