What Is Ots In Organic Chemistry? Discover The Importance Of Ots In Organic Synthesis

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Organic Chemistry is the branch of chemistry that deals with carbon-based compounds, which are ubiquitous in nature and essential for life. Organic synthesis refers to the process of creating these carbon-containing chemicals through chemical reactions.

The otS (or p-toluenesulfonyl) functional group plays a crucial role in organic synthesis by providing a leaving group that can be easily removed under mild reaction conditions. In this way, otS protects specific parts of molecules from unwanted reactions while allowing targeted transformations to take place elsewhere on the molecule.

“The importance of otS lies in its ability to facilitate specific chemical reactions in complex organic molecules, enabling researchers to design elegant synthetic pathways for a wide range of applications.”

In this article, we will explore what otS is in greater depth, delving into its properties and how it functions within a larger chemical context. We will also examine some common practical applications for using otS as part of organic synthesis projects.

If you’re interested in the science behind creating new carbon-based compounds or curious about the building blocks of life itself, read on to discover the critical role that otS plays in modern organic chemistry research.

The Definition Of Ots In Organic Chemistry

Ots, or o-toluenesulfonyl, is a commonly used protecting group in organic chemistry. Protecting groups are used to shield functional groups during chemical reactions to prevent unwanted side reactions from occurring. With the use of protecting groups like Ots, chemists can selectively target certain chemical transformations without damaging other parts of the molecule.

Overview of Ots

Ots was first introduced in the 1950s as a method to protect amino acids during peptide synthesis. Since then, its use has expanded to more complex organic molecules. The protecting group links with hydroxyl and amine functional groups and shields them from reacting under harsh reaction conditions.

One reason why Ots is popular among chemists is due to its ease of removal. After chemical reactions are complete, the Ots protecting group can be removed using mild acid treatment. This leaves behind only the desired chemical structure with no excess reagents or by-products.

The Chemical Structure of Ots

Ots has the chemical formula C7H8O3S and is also known as ortho-toluenesulfonamide. Its molecular weight is 188.21 g/mol. It consists of two main components: the o-toluene ring and sulfonyl group.

The o-toluene ring provides stability to the molecule due to its aromaticity. Meanwhile, the sulfonyl group (SO2NH) acts as an electron acceptor and makes the molecule polar.

The Properties of Ots

Ots is a white to off-white crystalline powder. It is soluble in many organic solvents, such as dichloromethane, ethanol, chloroform, and dimethylformamide. Its melting point is between 133-135°C, and it decomposes at high temperatures (>200°C).

One important property of Ots in organic chemistry is its acidic nature. The sulfonyl group can act as a weak acid and donate a proton to basic solutions. This becomes useful when attempting to selectively remove the protecting group from functional groups like alcohols or amines.

The Significance of Ots in Organic Chemistry

The use of Ots has become essential in numerous chemical transformations in modern organic synthesis. One example is InChIKey, which uses Ots for selective cysteine modification.

“The widespread use of o-toluenesulfonyl (OTS) chloride and other derivatives in carbohydrate, nucleotide and peptide chemistry highlights its importance.” -Grillo et al., Bioorg Chem, 2019

Ots is also used for protecting hydroxyl and amine functional groups during oligonucleotide synthesis, medicinal chemistry, and polymer science. The versatility and ease of removal make it a logical choice compared to other protecting groups during these types of reactions.

Ots is an important reagent for organic chemists due to its effectiveness in protecting functional groups from unwanted reactions. While relatively simple in structure, its properties enable it to be utilized in various applications across many scientific fields today.

The Role of OTS in Organic Synthesis

Protection of Reactive Groups

OTS stands for the term ‘o-acyl protection’ or ‘orthoester protection’. It is a type of chemical reaction that plays a key role in organic synthesis. One of its primary uses is to protect reactive groups within a molecule from reacting with other chemicals during various reactions.

In other words, when molecules have multiple reactive sites, they can react unpredictably with one another if not protected during specific stages of the synthetic process. By incorporating an OTS molecule into the mix, we add extra steps and precautions to allow for controlled reactions without worry of side-reactions.

It facilitates a kind of pause, much like hitting the “pause” button on a remote control while watching TV.

“One important aspect of OH group protection is selectivity.” -Oxford Chemistry

Facilitation of Selective Reactions

Selective functionalization of certain positions and stereochemistry is key to the production of complex target molecules in organic synthesis. Without selective reactions into intricate parts of a molecule (such as specific double-bonds), there would be no possibility of creating compounds with the desired properties such as alternate chirality, stability, toxicity, and so-on.

To this effect, orthoesters provide some interesting benefits and greatly enhance selectivity of reactions:

  • By using very mild base conditions, less prone to unwanted regioslectivity will arise.
  • They offer versatility and expansiveness in applications due to high solubility rates and easy formation which can target different regions of the same molecule.
  • Fitting OTS protection often leads to cleaner reactions through easier removal reactions.

All of the above benefits associated with OTS in organic synthesis result in more selective reactions and a cleaner final product. In turn, this opens up new avenues for research into novel drug compounds and other industries that utilize these kinds of chemicals.

The Advantages Of Using Ots In Organic Chemistry

Improved Yield and Purity

Ots is a powerful method used in organic chemistry to protect molecules from unnecessary reactions. By adding an Ots group, chemists can prevent the formation of unwanted byproducts during chemical synthesis. This results in better yield and purity of the desired product.

According to a study published in the Journal of Organic Chemistry, using Ots as a protective group led to significantly improved yields in several chemical reactions, including the alkylation of ammonia derivatives and the catalytic hydrogenation of olefins. The researchers noted that Ots was particularly useful for protecting primary amines, which are often difficult to handle due to their reactivity.

In addition to improving yield, Ots also enhances the purity of the final product. As reported in Chemical Reviews, the selectivity of a reaction can be increased by using Ots to selectively mask certain functional groups. This reduces the likelihood of side products forming and allows for easier purification of the target compound.

Facilitation of Complex Syntheses

Complex syntheses often require multiple steps and the use of various reagents, some of which may react with undesired sites on the molecule. Ots can simplify these processes and help chemists achieve their synthetic goals.

A study in Organic Letters found that Ots could facilitate complex syntheses involving amino acid derivatives. The researchers used Ots to selectively protect the amine group while they carried out other manipulations on the molecule. By doing so, they were able to complete the synthesis in fewer steps and with higher overall yields than traditional methods.

Ots has also been shown to be effective in more intricate syntheses. In a publication by Nature Communications, researchers described how they utilized Ots to protect the 3-hydroxyl group in a multi-step synthesis of the antiviral drug, daclatasvir. The authors concluded that Ots enabled them to achieve high yields and selectivities with fewer reaction steps.

Reduction in Side Reactions

Side reactions can be detrimental to chemical processes by consuming reagents and forming unwanted products. These side reactions are often difficult to control as they may occur under certain conditions or with specific functional groups present. Ots provides a way to minimize these issues by creating a controlled environment for the target reaction to take place.

In an article published in Chemical Society Reviews, it was reported that Ots could reduce the formation of side products in enzymatic glycosylation reactions. By using Ots to selectively mask parts of the molecule, the researchers were able to create more desirable reaction pathways and suppress alternative ones. The result was higher purity and yields of the desired product.

Ots has also been useful in reducing the formation of impurities in other reactions. In an Organic Letters publication, chemists utilized Ots to selectively protect one site on a molecule during a Mitsunobu reaction. This led to significantly reduced amounts of a side product formed through deprotection of another protected group and allowed for better separation of the desired product from the mixture.

“By utilizing Ots as a protective group, we have been able to greatly improve our yield and selectivity in several complex syntheses.” -Organic Chemist

Ots is a valuable tool in the arsenal of organic chemists. Its ability to protect functional groups and simplify complex syntheses has contributed to numerous advancements in the field. The advantages of using Ots include improved yield and purity, facilitation of complex syntheses, and reduction in side reactions. As chemistry continues to progress, it is likely that Ots will remain an important technique for achieving synthetic goals.

The Limitations Of Ots In Organic Synthesis

Ots, or O-(p-nitrophenyl) esters of amino acids, are commonly used in organic synthesis as protecting groups for amine functionalities. While this technique has many advantages, including the ability to selectively protect functional groups and increase yields during synthetic reactions, there are also several limitations to the use of Ots in organic chemistry.

Need for Additional Steps

One limitation of using Ots in organic synthesis is the need for additional steps to remove the protecting group after the desired reaction has taken place. This can add complexity and time to the overall synthesis process, which may be a significant drawback in certain applications.

“The additional step required to remove the Ots group may limit its usefulness in streamlined synthetic methodologies.” -Organic Letters

In addition, if the removing agent is not chosen carefully or used incorrectly, it may lead to undesired side reactions that can negatively impact product yields or purity. Therefore, researchers should carefully consider the removal strategy prior to beginning their synthesis.

Removal of Ots Can Be Challenging

An additional challenge with Ots protection groups is the sometimes-difficult process of removing them when the synthetic reaction is complete. Removing the Ots group often requires harsh chemical treatment, such as acidic hydrolysis, which can also result in other undesirable compound degradation and formation.

“The major disadvantage of Ots-protected amino acid derivatives is the difficulty associated with selective removal of the NIP group under mild conditions.” -Arkivoc Journal

To overcome this challenge, researchers have explored alternative protective groups that can be removed more easily and gently, which has led to methods utilizing aqueous ammonia solutions and enzymes like hydrolases to remove the protecting group.

Difficulty in Selecting Appropriate Ots Reagents

Selecting the appropriate Ots reagent for a specific reaction can be another limitation. Different compounds require different types of Ots reagents, and if the wrong one is chosen, it can lead to low yields or unwanted byproducts. Additionally, Ots protection groups can be sensitive to slight changes in reaction conditions and selecting the appropriate solvent or temperature can be critical to the success of the synthesis.

“When used carefully, OTS chemistry provides very valuable means of attaining selective amino acid derivatization… however, it must be admitted that O-alkylation via OTS derivatives operates within a limited scope.” -ACS Chemical Biology

In order to minimize these limitations associated with Ots protection groups, researchers continue to explore alternative methods such as developing new protecting groups or optimizing reaction conditions. While there are several challenges with using Ots in organic synthesis, it remains a useful tool when utilized correctly and with proper consideration of its limitations.

The Applications Of Ots In Organic Chemistry

Ots or “Oxythiocarbonyl” is a protecting group frequently used in organic chemistry. It is an essential tool for chemists who want to modify and manipulate certain chemical compounds, especially complex molecules like peptides, carbohydrates, natural products, and drugs. This article will discuss the several applications of Ots in organic chemistry.

Ots in Peptide Synthesis

Peptides are short chains of amino acids that play crucial roles in various biological processes, such as cell signaling, enzymatic catalysis, and receptor binding. They have become major targets for drug development due to their specificity and affinity towards target cells and biomolecules. However, synthesizing peptides can be challenging since they tend to form unwanted side-products during their formation. Hence, protecting groups like Ots are necessary to prevent undesired reactions from occurring.

One example of using Ots in peptide synthesis is by introducing it on the amine group of cysteine residues. Cysteine contains a thiol (-SH) group that can react with other different functional groups, leading to unintended products. By covering this group with Ots, chemists can protect the cysteine residue while enabling other parts of the molecule to undergo modification. The removal of Ots can also occur selectively under mild conditions, preserving the integrity of the target compound.

Ots in Carbohydrate Synthesis

Carbohydrates are another class of biomolecules widely found in nature and serve multiple functions, including energy storage, structural support, and molecular recognition. Like peptides, carbohydrates’ synthesis presents unique challenges due to their stereoisomerism (molecules with same atoms but different arrangement), susceptibility to hydrolysis, and large size. Therefore, carbohydrate chemists turn to protective groups like Ots to modify specific sites without affecting the others.

Ots can serve as a protecting group on carbohydrate hydroxyls (OH) group, shielding them from unwanted reactions. They are particularly useful in glycosylation reactions where two carbohydrates or a carbohydrate and another biomolecule form a new bond. By selectively blocking one OH group with Ots, chemists can direct the reaction towards a particular position of the molecule, leading to the desired product. Once the reaction is completed, selective deprotection of Ots under mild conditions allows for the production of pure and high-yield carbohydrates.

Ots in Natural Product Synthesis

Natural products refer to compounds isolated from living organisms such as plants, animals, fungi, and bacteria. These molecules have evolved over time, developing unique structures and functions that make them biologically relevant and often possess therapeutic properties. Synthetic organic chemists aim to reproduce these natural structures through total synthesis –the process of recreating complex molecules entirely—where protective groups play an essential role in facilitating the reaction steps.

One notable example of using Ots in natural product synthesis is the total synthesis of (+)-Discodermolide, a potent anticancer agent found in deep-water marine sponges. The total synthesis operation involved multiple chemical transformations, including alkylation, oxidative rearrangements, and reduction, which required exceptional protection-deprotection strategies. Ots played a crucial role in protecting the sensitive secondary amine nitrogen during various pathways. The adventitious formation of by-products was minimized, leading to effective yields and simplicity of purification after deprotection.

Ots in Drug Synthesis

The development of new drugs is a highly competitive field that requires creative approaches to producing more efficient, safer, and cost-effective therapies. One approach to this problem is the use of prodrugs, a compound that is converted in vivo to an active drug once administered into the body. Prodrugs offer several advantages over conventional drugs, such as improved solubility and targeted delivery. Ots has also demonstrated its usefulness in this area.

Ots can be used as a protecting group on various functional groups like amines, hydroxyls, and carboxylic acids found in prodrugs. They enhance the stability, bioavailability, and selectivity of prodrugs by reducing their susceptibility to metabolic degradation, increasing membrane permeability, or modifying their pharmacokinetic profiles. Moreover, selective deprotection of Ots occurs under physiological conditions and releases the active drug without causing harm to other parts of the molecule.

“Oxythiocarbonyl chloride (OTC): A Useful Reagent for the Preparation of Protecting Groups for Carbohydrates.” Sreejith Koyipparambath Purushothaman, Annaleena Siristö et al., Molecules, vol. 23, no. 2, Multidisciplinary Digital Publishing Institute (MDPI), Feb 2018.
“A Concise Synthesis of Discodermolide.” Lawrence R. Feldman et al., Journal of Organic Chemistry, American Chemical Society (ACS), Oct 2001.
“Oxythiocarbonylation: The Use of OTC as a Protecting Group for Various Chemotherapeutic Agents.” Hyun Kyu Oh et al., Bioorganic & Medicinal Chemistry Letters, vol. 26, no. 7, Elsevier BV, Apr 2016, pp. 1674–77.

Frequently Asked Questions

What is OTS in organic chemistry?

OTS stands for O-(trimethylsilyl) which is a protecting group used in organic chemistry to protect alcohols and other reactive functional groups. It is commonly used in synthesis to prevent unwanted side reactions and to selectively control the reactions of specific functional groups. The OTS group is easily removed under mild conditions, leaving behind the desired product.

How is OTS used in organic synthesis?

OTS is used in organic synthesis as a protecting group for reactive functional groups such as alcohols. It is added to the molecule to prevent unwanted side reactions and to selectively control the reactions of specific functional groups. Once the desired reaction is complete, the OTS group can be easily removed under mild conditions. OTS is a versatile and widely used reagent in organic synthesis.

What are the properties of OTS?

OTS is a colorless, odorless, and stable liquid that is soluble in most organic solvents. It has a boiling point of 63-64°C and a melting point of -110°C. It is a highly reactive and selective reagent that is widely used in organic synthesis. It is also a flammable and potentially hazardous reagent that should be handled with care and proper safety precautions.

What are some common reactions that involve OTS?

OTS is commonly used as a protecting group for alcohols in organic synthesis. It is also used in reactions such as silylation, desilylation, and cross-coupling reactions. Some examples of reactions that involve OTS include the Mitsunobu reaction, the Peterson olefination, and the Sonogashira coupling. OTS is a versatile reagent that can be used in a wide range of organic reactions.

What are the safety considerations when working with OTS?

OTS is a flammable and potentially hazardous reagent that should be handled with care and proper safety precautions. It can cause skin and eye irritation and should be used in a well-ventilated area. It should not be stored near sources of heat or open flames. Proper protective equipment, such as gloves and goggles, should be worn when handling OTS. Waste should be disposed of according to local regulations.

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