Mitsonobu reagents
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Novasep Synthesis Proprietary Products: Mitsunobu Reagents
Mitsunobu Reagents
DBAD-Dibenzylazodicarboxylate
DIAD-Diisopropylazodicarboxylate
ADDP-Azodicarbonyldipiperidide
| DBAD | DIAD | ADDP |
 |
 |
 |
| DBAD | DIAD | ADDP | |
| Formula | C16H14N2O4 | C8H14N2O4 | C12H20N4O2 |
| Molecular Mass | 298.3 g/mol | 202.2 g/mol | 252.3 g/mol |
| CAS-No. | [2449-05-0] | [2446-83-5] | [10465-81-3] |
| EINECS | 219-508-0 | 219-502-8 | not registered |
| Scale of Development | Commercial | Commercial | 10 - 100 kg |
Specification
| DBAD | DIAD | ADDP | |
| Appearance | Intensive yellow crystalline solid | Orange to red liquid | Yellow crystal solid |
| Identity | conforms | ||
| Assay | >94.0 % (UV) | >93.0 % (GC) | >= 96 % (HPLC) |
Transport Information
| DBAD | DIAD | ADDP | |
| Transport classification | Non dangerous goods | UN-No.: 3082 | Non dangerous goods |
| Packaging | Fibre drums, 50 kg | 50 kg steel drums | Fibre drums, PE-Inliner, 50 kg or smaller |
Quality / Regulatory
These are non-GMP products. The synthesis of these products can be performed under c-GMP upon request / agreement. Please feel free to ask for more information.
Applications
Novasep Synthesis offers the full range of Mitsunobu reagents and offers the custom synthesis with Mitsunobu reagents.
DIAD is mostly used, a non-hazardous liquid easiest to dose, safest to handle, commercially the best bargain and, compared with alternatives, generating the lowest amount of waste.
Used in the synthesis of drugs such as: anticancer, antiviral (HIV), anti-obesity, anti-allergic, ophthalmic, anti-psoriatic, cardiovascular, osteoarthritis, lipoprotein disorders and type II diabetis.
- Support to choose the effective combination of educt, diazo-compound and phosphine component
- Synthon for amino functions
The Mitsunobu reaction is a well-established fundamental condensation reaction in organic
chemistry.
The Mitsunobu reaction allows the conversion of complex primary and secondary alcohols to esters, phenyl ethers, thioethers, and the synthesis of heterocycles like aziridines, lactones and lactames under mild reaction conditions.
The broad variety of the Mitsunobu reactions also allows the conversion with phenols, imides, thioles, thio-amides or β-ketonic esters as the nucleophilic compound.
The classical Mitsunobu reaction (with DEAD and PPh3) has as limitation factor - the pKa of the nucleophilic compound. The reaction runs well with pKa > 11, if the pKa < 11, the reaction does not run or only with lower yields. With new Mitsunobu reagents and other phosphine compounds, the range of reactions is enlarged.
| Reagents | Reaction time | Reaction temperature |
Yield |
| DEAD; Ph3P | 2.5 h | r.t. | - |
| DEAD; Bu3P | 2.5 h | r.t. | 13% |
| DIAD; Bu3P | 2.5 h | 0°C - r.t. | 22% |
| DIAD; Me3P | 2.5 h | 0°C - r.t. | 27% |
| ADDP; Bu3P | 2.5 h | 0°C - r.t. | 28% |
| ADDP; Me3P | 1.5 h | 0°C - r.t. | 38% |
With other reaction partners the yields is up to 91 %
Schips, C; Dissertation, Univ. Tübingen, 2005
An advantage of the trialkylphosphine compound is the easy removal of the phosphine oxide from the reaction mixture by aqueous work up.
An important application of the Mitsunobu reaction is the inversion of the stereochemistry of chiral secondary alcohols. This is used in the chemistry of natural products for the purposeful inversion of stereochemistry.
Advantages of DIAD versus other Mitsunobu reagents:
- DIAD is non hazardous goods, DEAD is explosive
- DIAD is liquid - easy dosage
- DIAD is produced in commercial quantities
- DIAD is the best commercial alternative
Contact
Examples
A convenient Two-Step Procedure for the Synthesis of Substituted Allylic Amines from Allylic Alcohols
S. E. Sen, S. L. Roach, Synthesis, 1995, 756-758.
The intramolecular variant of the Mitsunobu reaction can also give access to lactones and lactames.
Synthesis of N-H vinylaziridines
B. Olofsson, R. Wijtmans, P. Somfai, Tetrahedron, 2002, 58, 5979-5982.
The Mitsunobu reagents can also be used for the introduction of amino or hydrazine groups into aliphatic or aromatic systems.
Synthesis of Minocycline
US 3403179 (1968)
Reagents: DBAD-Dibenzylazodicarboxylate
| Formula | C16H14N2O4 |
| Molecular Mass | 298.3 g/mol |
| CAS-No. | [2449-05-0] |
| EINECS | 219-508-0 |
| Scale of Development | Commercial |
Specification
| Appearance | intensive yellow crystalline solid |
| Identity | conforms (IR) |
| Purity | |
| Assay | >= 94.0 % (UV) |
Transport Information
| Transport classification | Non dangerous goods according to transport regulations |
| Packaging | Fibre drums, 50 kg |
| Sample Size | 50 g or 1 kg |
| Availability | Samples available |
Reagents: DIAD-Diisopropylazodicarboxylate
| Formula | C8H14N2O4 |
| Molecular Mass | 202.2 g/mol |
| CAS-No. | [2446-83-5] |
| EINECS | [219-502-8] |
| Scale of Development | Commercial |
Specification
| Appearance | orange to red liquid |
| Identity | conforms (IR) |
| Purity | |
| Cyclohexane | <= 1 % (GC) |
| Other impurities | <= 6 % (GC) |
| Assay | > 94.0 % (GC) |
Transport Information
| Transport classification | UN-No.: 3082 Class: 9 |
| Packaging | 50 kg steel drums |
| Sample Size | 50 ml or 1 l |
| Availability | Samples available |
Reagents: ADDP-Azodicarbonyldipiperidine
| Formula | C12H20N4O2 |
| Molecular Mass | 252.3 g/mol |
| CAS-No. | [10465-81-3] |
| EINECS | not registered |
| Development stages: | Pilot scale |
Specification
| Appearance | yellow crystalline solid |
| Identity | conforms (IR) |
| Purity | |
| Water (KF) | < 0.1 % (UV) |
| Melting point | > 129°C |
| Assay | >= 96 % (HPLC) |
Transport Information
| Transport classification | Non dangerous goods according to transport regulations |
| Packaging | Fibre drums, , PE-Inliner, 50 kg |
| Sample Size | 50 g or 1 kg |
| Availability | Samples available |
Mitsunobu reagents
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