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Protective Group




In many preparations of delicate organic compounds, some specific parts of their molecules cannot survive the required reagents or chemical environments. Then, these parts, or groups, must be protected. For example, Lithium Aluminum Hydride is a highly reactive but useful reagent capable of reducing Ester s to Alcohol s. It will always react with Carbonyl groups, and this cannot be discouraged by any means. When a reduction of an ester is required in the presence of a carbonyl, the attack of the hydride on the carbonyl has to be prevented. For example, the carbonyl is converted into an Acetal , which does not react with hydrides. The acetal is then called a '''protecting group''' for the carbonyl. After the step involving the hydride is complete, the acetal is removed (by reacting it with an aqueous acid), giving back the original carbonyl. This step is called '''deprotection'''.

Protecting groups are more commonly used in small-scale laboratory work and initial development than in industrial production processes because their use adds additional steps and material costs to the process.


COMMON PROTECTING GROUPS


Alcohol protecting groups

Protection of Alcohols :


Amine protecting groups

Protection of Amine s:


Carbonyl protecting groups

Protection of Carbonyl groups:
  • Acetal s and Ketal s - Removed by acid. Normally, the cleavage of acyclic acetals is easier than of cyclic acetals.

  • Acylal s - Removed by Lewis Acid s.

  • Dithiane s - Removed by metal salts or oxidizing agents.



Carboxylic acid protecting groups

Protection of Carboxylic Acid s:
  • Methyl esters - Removed by acid or base.

  • Benzyl esters - Removed by hydrogenolysis.

  • ''tert''-Butyl esters - Removed by acid, base and some reductants.

  • Silyl esters - Removed by acid, base and Organometallic reagents

  • Miscellaneous



ORTHOGONAL PROTECTION

Orthogonal protection is a strategy allowing the deprotection of multiple protective groups one at the time each with a dedicated set of reaction conditions without affecting the other. It was introduced in the field of orthogonal deprotection is demonstrated in a Photochemical Transesterification by Trimethylsilyldiazomethane utilizing the Kinetic Isotope Effect ''Isotope Effects in Photochemistry: Application to Chromatic Orthogonality''
Aurélien Blanc and Christian G. Bochet Org. Lett. ; 2007; 9(14) pp 2649 - 2651; (Letter) :
:
Due to this effect the Quantum Yield for deprotection of the right-side ester group is reduced and it stays intact. Significantly by placing the deuterium atoms next to the left-side ester group or by changing the wavelength to 254 nm the other monoarene is obtained.


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