DAST-Mediated Amidation at Room Temperature: Method Features, Practical Value, and Scope of Applicability

I. Why This DAST-Mediated Amidation Method Merits Attention

Amide bond formation is one of the most common fundamental transformations in organic synthesis, medicinal chemistry, and the preparation of functional molecules. In efforts to improve amidation reactions, the central questions have remained the same: can additional activation steps be reduced, can the burden of byproducts be lowered, and can the conditions be made milder with a more straightforward workup. Reviews on nonclassical amide bond formation and green amidation have both emphasized that, although traditional coupling-reagent-based routes are well established, there is still room for continued optimization in terms of efficiency, sustainability, and operational simplicity. This is also an important reason why nonclassical amide bond formation, catalytic direct amidation, and green amidation continue to attract attention.[3][5][6]

A 2025 Organic Letters paper showed that DAST (Diethylaminosulfur trifluoride) can promote the formation of amides from carboxylic acids and amines in dichloromethane at room temperature, and no additional base is required in the system reported in that paper. Using equimolar amounts of carboxylic acid and amine as starting materials, the method is applicable to various fluorinated aliphatic acids, fluorinated aromatic acids, as well as primary amines, secondary amines, and electron-deficient amines. It can also be used for the late-stage amidation of fatty acid amides, drug molecules, and more than ten drug-related building blocks.

[1] Kumawat, S.; Jyothi, K. L. M. N. S.; Kalevaru, V. N.; Wohlrab, S.; Natte, K. DAST Enabled Synthesis of Fluorinated Amides and Fatty Acid Amides Including Drugs under Ambient Conditions. Organic Letters, 2025, 27(32), 8829–8834. DOI: 10.1021/acs.orglett.5c02144.

The significance of this work lies in the fact that DAST serves here as a carboxylic acid activating reagent; this method is more appropriately understood as an in situ acyl fluoride formation–amidation pathway. As an important class of carboxylic acid derivatives, acyl fluorides have increasingly been used in recent years for amidation, esterification, and other downstream transformations because they offer a favorable balance between stability and reactivity.[1][2]

Key points at a glance for DAST-mediated amidation at room temperature

Core Question	Key Conclusion
What does this work investigate?	A DAST-mediated room-temperature amidation reaction between carboxylic acids and amines.
How should this reaction be understood?	It is better viewed as an in situ acyl fluoride formation–amidation process rather than a conventional coupling-reagent-mediated amidation reaction.
What are the standout features of the method?	Room temperature, dichloromethane, equimolar carboxylic acid and amine, no additional base required in the system reported in the paper, scalable, and no complicated workup after the reaction.
What are the main practical values?	Synthesis of fluorinated amides, fatty acid amides, and late-stage amidation of drug molecules and drug-related building blocks.
What requires special attention?	This method has clear practical value, but at present it is better regarded as a representative complement to existing amidation methods rather than a universal replacement; at the same time, the safety and handling requirements of DAST cannot be ignored.

II. What Role Does DAST Play in Room-Temperature Amidation?

DAST is a highly classical fluorine-containing reagent in organofluorine chemistry. Early studies showed that such dialkylaminosulfur fluorides can convert hydroxyl groups or carbonyl oxygen atoms into fluorinated products under relatively mild conditions; subsequent technical sources and reviews have also categorized DAST as a common classical deoxofluorinating reagent.[8][9]

In this 2025 study, the key role of DAST is not the conventional construction of C–F bonds, but rather the promotion of carboxylic acid conversion into an intermediate that is more prone to acyl transfer. The key information given in the abstract is that the reaction proceeds in dichloromethane at room temperature, uses equimolar amounts of carboxylic acid and amine, requires no additional base in the reported system, and covers various fluorinated acids, fatty acid amides, and drug-related examples.[1]

III. To Understand This Reaction, the Key Lies in the In Situ Acyl Fluoride Formation Process

Acyl fluorides are central to understanding this pathway. Reviews on acyl fluorides have pointed out that they are highly valuable synthetic intermediates and have increasingly been used in peptide synthesis, more challenging esterification and amidation reactions, as well as several transition-metal-catalyzed transformations.[2]

From the standpoint of reaction design, the reason acyl fluorides are well suited as an activated form of carboxylic acids is that they are generally somewhat more stable than acyl chlorides while still retaining high acyl-transfer reactivity. Relevant reviews regard this “balance between stability and reactivity” as one of the key values of acyl fluoride chemistry.[2][4]

IV. What Practical Value Does DAST-Mediated Amidation at Room Temperature Offer?

The practical value of this method is first reflected in its relatively simple conditions: the reaction can be carried out at room temperature in dichloromethane using equimolar amounts of carboxylic acid and amine, and no additional base is required in the system reported in the paper. At the same time, the authors also emphasized that this is a scalable amidation method that does not require a complicated workup after the reaction.

For experimental chemists, the significance of these features is that the method design is more direct, the operational burden is relatively low, and it is more convenient to bring into actual route screening and substrate expansion.

From the perspective of substrates and applications, this method is noteworthy in at least three respects.

1. It is suitable for the synthesis of fluorinated amides, and the paper particularly highlights applications to fluorinated aliphatic acids and fluorinated aromatic acids.

2. It is suitable for the preparation of fatty acid amides, and the authors reported the synthesis of fatty acid amide derivatives.

3. It can also be extended to the late-stage amidation of drug molecules and drug-related building blocks; the abstract states that the method can be applied to commercial drugs and more than ten drug-related building blocks.

The table below can be used to compare the DAST-mediated room-temperature amidation method with several common amidation routes, making it easier to understand the practical position and applicable scenarios of this method.

Method Concept	Common Features	Relative Position of This DAST Route
Preformed acyl chloride route	High reactivity, but often requires an additional preparation step and is sensitive to moisture and some functional groups	The DAST route does not require prior isolation of an acyl chloride and instead emphasizes in situ activation and one-pot completion
Traditional coupling-reagent route	Mature and broadly applicable, but often accompanied by stoichiometric byproducts and purification burden	The appeal of the DAST route lies in room-temperature conditions, equimolar reactants, and no complicated workup after the reaction
In situ acyl fluoride formation–amidation route	Uses acyl fluorides to balance reactivity and operational convenience	The DAST work represents a new implementation within this category
Main limitations of the DAST route	Not a universally substitutable solution for all substrate combinations, and the reagent has higher safety requirements	It is best understood as a “representative complementary route” rather than a universal replacement

V. The Novelty and Scope Boundaries of the DAST-Mediated Room-Temperature Amidation Method

The novelty of this method is mainly reflected in three aspects.

1. It does not follow the commonly used coupling-reagent or acyl chloride activation systems; instead, it applies the classical fluorinating reagent DAST to carboxylic acid activation and amidation.

2. This method emphasizes room temperature, equimolar amounts of carboxylic acid and amine, and, in the system reported in the paper, does not require any additional base.

3. The demonstrated applications include not only fluorinated carboxylic acids and fatty acid substrates, but also extend to the late-stage amidation of fatty acid amides, drug molecules, and drug-related building blocks.

The significance of this method is more appropriately understood as follows: it provides a new implementation pathway for in situ acyl fluoride formation–amidation. Before the DAST approach, studies had already achieved one-pot amidation of carboxylic acids via in situ acyl fluoride formation using Deoxo-Fluor and pentafluoropyridine, respectively. At the same time, the evaluation of direct amidation methods should not rely only on a single conditional advantage, but should instead be judged comprehensively in light of substrate scope, condition compatibility, and practical operability.

VI. What Safety and Operational Issues Should Be Considered When Using DAST?

When discussing DAST, one should not focus only on its convenience in amidation reactions, but must also recognize its safety requirements. Publicly available product information shows that DAST is highly corrosive and can cause severe damage to the skin, eyes, mucous membranes, and lung tissue. It reacts violently with water or moisture to release HF, and may undergo violent decomposition above 50 °C.

Although this method can be carried out at room temperature, that does not mean the operational risk is low. When understanding or adopting this type of method, careful attention must still be paid to anhydrous conditions, fume hood operation, personal protective equipment, and temperature control. For experimental chemists, these requirements are just as important as substrate scope, yield, and workup.

VII. Reference Sources and Further Reading

The table below links the main statements in the main text with their corresponding references for easier verification and further reading.

Main Statement	Corresponding References
Amidation reactions are still pursuing more direct, simpler, and more sustainable routes	[3], [5], [6]
Reaction conditions, substrate scope, and applications to drugs and late-stage amidation in the 2025 DAST study	[1]
The importance of acyl fluorides in amidation, esterification, and other downstream transformations	[2], [4]
Background of DAST as a classical fluorinating/deoxofluorinating reagent	[8]
The DAST route is not the only precedent in this direction; Deoxo-Fluor and PFP have already provided related implementation pathways	[4], [7]
Corrosiveness of DAST, its hazards upon contact with water or moisture, and its thermal sensitivity	[9]

References:

[1] Kumawat, S.; Jyothi, K. L. M. N. S.; Kalevaru, V. N.; Wohlrab, S.; Natte, K. DAST Enabled Synthesis of Fluorinated Amides and Fatty Acid Amides Including Drugs under Ambient Conditions. Organic Letters 2025, 27 (32), 8829–8834. DOI: 10.1021/acs.orglett.5c02144.

[2] Gonay, M.; Batisse, C.; Paquin, J.-F. Recent Advances in the Synthesis of Acyl Fluorides. Synthesis 2021, 53 (4), 653–665. DOI: 10.1055/s-0040-1705951.

[3] de Figueiredo, R. M.; Suppo, J.-S.; Campagne, J.-M. Nonclassical Routes for Amide Bond Formation. Chemical Reviews 2016, 116 (19), 12029–12122. DOI: 10.1021/acs.chemrev.6b00237.

[4] Brittain, W. D. G.; Cobb, S. L. Carboxylic Acid Deoxyfluorination and One-Pot Amide Bond Formation Using Pentafluoropyridine (PFP). Organic Letters 2021, 23 (15), 5793–5798. DOI: 10.1021/acs.orglett.1c01953.

[5] Sabatini, M. T.; Boulton, L. T.; Sneddon, H. F.; Sheppard, T. D. A Green Chemistry Perspective on Catalytic Amide Bond Formation. Nature Catalysis 2019, 2 (1), 10–17. DOI: 10.1038/s41929-018-0211-5.

[6] Wang, X. Challenges and Outlook for Catalytic Direct Amidation Reactions. Nature Catalysis 2019, 2 (2), 98–102. DOI: 10.1038/s41929-018-0215-1.

[7] White, J. M.; Tunoori, A. R.; Turunen, B. J.; Georg, G. I. [Bis(2-methoxyethyl)amino]sulfur Trifluoride, the Deoxo-Fluor Reagent: Application toward One-Flask Transformations of Carboxylic Acids to Amides. The Journal of Organic Chemistry 2004, 69 (7), 2573–2576. DOI: 10.1021/jo035658k.

[8] Middleton, W. J. New Fluorinating Reagents. Dialkylaminosulfur Fluorides. The Journal of Organic Chemistry 1975, 40 (5), 574–578. DOI: 10.1021/jo00893a007.

[9] Tokyo Chemical Industry Co., Ltd. Safety Data Sheet: (Diethylamino)sulfur Trifluoride [Fluorinating Reagent]; Product No. D1868; Revision date: March 4, 2023.

VIII. Product Navigation for DAST-Mediated Amidation at Room Temperature (Tables 1–4)

Research Task / Experimental Objective	Problem Usually to Be Solved	Recommended Priority	Navigation Notes
Establish a basic DAST-mediated room-temperature amidation reaction	To first set up the reaction system and identify the core reagents, solvent, mechanistically relevant components, and key intermediates	Table 1	Table 1 brings together DAST, dichloromethane, related deoxofluorination/in situ acyl fluoride formation reagents, representative acyl fluorides, and mechanistically relevant components, making it suitable for quickly grasping the core chemical logic of this route.
Understand why this route differs from traditional coupling-reagent methods or acyl chloride methods	To clarify the distinctive features of the DAST route and how it differs from routes based on DCC, CDI, HATU, oxalyl chloride, thionyl chloride, and related reagents	Table 1 + Table 4	Table 1 reflects the main line of in situ acyl fluoride formation–amidation, while Table 4 reflects traditional carboxylic acid activation and coupling systems; taken together, the two tables are suitable for comparative analysis of methods and route selection.
Select carboxylic acid substrates for method validation or substrate scope expansion	Uncertainty about which types of carboxylic acids to start with, and a need to identify representative substrates such as basic model acids, fluorinated acids, and fatty acids	Table 2	Table 2 organizes representative substrates by type, including basic carboxylic acids, fluorinated aliphatic acids, fluorinated aromatic acids, and long-chain fatty acids, making it suitable for substrate screening, substrate scope design in papers, and selection reference.
Carry out research related to the synthesis of fluorinated amides	To prepare difluoro-, trifluoro-, or fluorinated aromatic amides and examine the use of the DAST route in building fluorinated structures	Table 2 + Table 3	Table 2 provides sources of fluorinated carboxylic acid substrates, while Table 3 provides amine substrates and related amide molecules that can be paired with them; together they are suitable for research centered on “fluorinated carboxylic acid + amine → fluorinated amide.”
Carry out research on the preparation of fatty acid amides	To prepare the corresponding fatty acid amides from lauric acid, palmitic acid, stearic acid, oleic acid, and related substrates	Table 2 + Table 3	Table 2 focuses on medium- and long-chain fatty acid substrates, while Table 3 provides representative fatty acid amide products, making them suitable for substrate selection, product examples, and application description for fatty acid amide synthesis.
Select appropriate amine substrates to evaluate reaction applicability	To compare the performance of aromatic primary amines, aliphatic primary amines, cyclic secondary amines, and electron-deficient aromatic amines in this system	Table 3	Table 3 presents several representative classes of amine substrates, facilitating substrate applicability studies designed from the perspective of nucleophile type.
Focus on drug-related molecules or late-stage amidation applications	To show that this route is not limited to model substrates, but can also be extended to drug-related molecules and bioactive molecules	Table 3	Table 3 includes representative drug-related amide molecules and bioactive molecules, making it suitable for supporting a research line that extends “from basic methodology to drug-related applications.”
Study the mechanism of in situ acyl fluoride formation or the value of acyl fluoride intermediates	To explain mechanistically why DAST can promote amidation and why acyl fluoride intermediates are important	Table 1	Table 1 includes DAST, structurally related amine components, as well as benzoyl fluoride and representative fluorinated aromatic acyl fluorides, making it suitable for mechanistic discussion and expanded introduction to acyl fluoride chemistry.
Compare different in situ acyl fluoride formation strategies	To examine DAST together with routes based on Deoxo-Fluor, pentafluoropyridine, and related reagents	Table 1	Table 1 covers key representative chemicals related to in situ acyl fluoride formation, making it suitable for expanded discussion of “different implementation pathways for acyl fluoride formation.”

Table 1 | Core Deoxofluorination / In Situ Acyl Fluoride Formation Reagents, Acyl Fluoride Intermediates, Mechanistically Relevant Components, and Reaction Medium

Category	CAS No.	Aladdin Catalog No.	Name	Specification or Purity	Product Features and Applications
Reaction solvent	75-09-2	D433565	Dichloromethane	Anhydrous, ≥99.8%, containing 40–150 ppm amylene as stabilizer	One of the common solvents used in this type of DAST-mediated room-temperature amidation reaction; suitable for use with DAST under anhydrous conditions to activate carboxylic acids and maintain the in situ acyl fluoride formation–amidation system.
Core deoxofluorination / in situ acyl fluoride formation reagent	38078-09-0	D111067	(Diethylamino)sulfur trifluoride (DAST)	≥95%	The core reagent discussed in this article; under mild conditions it can mediate in situ activation of carboxylic acids and formation of acyl fluoride intermediates, which then react with amines to generate amides, making it the key chemical in the entire room-temperature amidation route.
Control reagent for deoxofluorination / in situ acyl fluoride formation	202289-38-1	B137512	Bis(2-methoxyethyl)aminosulfur Trifluoride	≥90%(T)	A representative Deoxo-Fluor-type reagent that can serve as a same-class comparison to DAST for comparing the use of different aminosulfur trifluoride reagents in carboxylic acid activation and in situ acyl fluoride formation.
Control reagent for in situ acyl fluoride formation routes	700-16-3	P136710	Pentafluoropyridine	≥98%(GC)	A representative reagent related to carboxylic acid deoxyfluorination / in situ acyl fluoride formation, useful as a comparison to the acyl fluoride formation strategy of the DAST route and for understanding different in situ acyl fluoride formation strategies.
Mechanistically relevant amine / byproduct component	109-89-7	D110469	Diethylamine	Distilled grade, ≥99.5%	A structurally related amine component of DAST and also a basic component worth noting in mechanistic discussion; useful for understanding acid–base balance in the system, HF capture, and potential sources of side reactions.
Acyl fluoride intermediate / control compound	455-32-3	B152051	Benzoyl Fluoride	≥98%	A classical representative aromatic acyl fluoride that can be used to understand the key intermediate logic of the DAST route—“carboxylic acid is first converted to an acyl fluoride, which then reacts with an amine to form an amide”—and also serves as a control compound for acyl fluoride routes.
Acyl fluoride intermediate / control compound	368-94-5	B694207	4-(Trifluoromethyl)benzoyl fluoride	≥97%	A representative aromatic acyl fluoride containing a trifluoromethyl group, suitable for illustrating representative structural types formed after fluorinated aromatic acids are converted into acyl fluoride intermediates in the DAST system.

Table 2 | Carboxylic Acid Substrates: Basic Model Acids, Fluorinated Carboxylic Acids, and Long-Chain Fatty Acids

Category	CAS No.	Aladdin Catalog No.	Name	Specification or Purity	Product Features and Applications
Model carboxylic acid substrate (basic aliphatic acid)	64-19-7	A116166	Acetic acid	Guaranteed reagent, ≥99.5%	One of the most basic model aliphatic acid substrates; suitable for establishing a basic understanding of DAST-mediated carboxylic acid activation and amidation, and also appropriate for condition comparison with traditional acyl chloride methods or coupling-reagent methods.
Aromatic carboxylic acid substrate	65-85-0	B433248	Benzoic acid	Suitable for synthesis	A classical model aromatic carboxylic acid substrate that can be used to examine the fundamental performance of DAST-mediated amidation of aromatic acids and also serves as a common control substrate for acyl chloride and coupling-reagent methods.
Fluorinated aromatic carboxylic acid substrate	456-22-4	F105089	4-Fluoro benzoic acid	Sublimed grade, ≥99%	A representative monofluoro-substituted aromatic acid substrate, suitable for constructing fluorinated aromatic amides and for examining the effect of electron-withdrawing fluorine substitution on the aromatic ring on reaction performance.
Fluorinated aromatic carboxylic acid substrate	455-24-3	T109781	4-(Trifluoromethyl)benzoic acid	≥98%	A representative trifluoromethyl-substituted aromatic acid substrate, suitable for constructing aromatic amides containing trifluoromethyl groups and illustrating the value of this method for the synthesis of fluorinated aromatic amides.
Fluorinated carboxylic acid substrate	76-05-1	T433655	Trifluoroacetic acid (TFA)	Anhydrous, ≥99%	A typical small-molecule fluorinated aliphatic acid substrate that can be used to construct amide frameworks featuring trifluoromethyl groups and also helps illustrate the significance of this route for fluorinated amide synthesis.
Fluorinated carboxylic acid substrate	381-73-7	D102056	Difluoroacetic Acid	≥98%	A typical small-molecule fluorinated aliphatic acid substrate that can be used to prepare difluoroacetamide products, illustrating a representative application of the DAST route in fluorinated amide synthesis.
Fluorinated carboxylic acid substrate	354-08-5	B183971	Bromodifluoroacetic acid	≥98%	A reactive fluorinated carboxylic acid substrate featuring difluoro substitution, suitable for constructing more functionally rich fluorinated amides and representing one of the characteristic fluorinated substrates discussed in this article.
Long-chain fatty acid substrate	143-07-7	L432090	Lauric acid	Moligand™, suitable for synthesis	A representative medium- to long-chain fatty acid substrate that can be used for the preparation of lauramide and related fatty acid amides, illustrating the practical utility of this method in the synthesis of fatty acid derivatives.
Long-chain fatty acid substrate	57-10-3	P753896	Palmitic acid	Stearic acid ≤0.5%	A representative long-chain fatty acid substrate that can be used in studies on the preparation of fatty acid amides, illustrating the value of the DAST route in amidation of hydrophobic fatty acids.
Long-chain fatty acid substrate	57-11-4	S432958	Stearic acid	Moligand™, suitable for synthesis	A typical saturated long-chain fatty acid substrate, suitable for constructing stearamide and related hydrophobic fatty acid amides, and applicable to studies of the DAST route in long-chain fatty acid systems.
Unsaturated long-chain fatty acid substrate	112-80-1	O491236	Oleic acid	Pharmaceutical grade, PharmPure™	A representative unsaturated fatty acid substrate that can be used to examine the compatibility of the DAST route with long-chain fatty acid systems containing double bonds and for preparing related products such as oleamide.

Table 3 | Amine Substrates, Representative Amide Products, and Drug-Related Amide Molecules

Category	CAS No.	Aladdin Catalog No.	Name	Specification or Purity	Product Features and Applications
Aromatic primary amine substrate	62-53-3	A112119	Aniline	Standard for GC, ≥99.9%(GC)	One of the most common aromatic primary amine substrates, suitable for establishing the basic substrate scope of DAST-mediated amidation involving aromatic amines.
Electron-withdrawing-substituted aromatic primary amine substrate	455-14-1	T100951	4-(Trifluoromethyl)aniline	≥98%	An aromatic primary amine substrate bearing a strongly electron-withdrawing trifluoromethyl group, suitable for examining the applicability of the DAST route to amidation involving electron-deficient aromatic amines.
Aliphatic primary amine substrate	100-46-9	B108477	Benzylamine	AR, ≥99%	A common primary amine substrate, suitable for evaluating the ability of aliphatic primary amines to capture acyl intermediates and undergo amidation efficiently in DAST-mediated in situ acyl fluoride formation systems.
Secondary amine substrate	110-91-8	M109058	Morpholine	Distilled grade, ≥99.5%	A representative cyclic secondary amine substrate, suitable for evaluating the applicability of DAST-mediated systems to amide formation via nucleophilic attack of secondary amines on acyl fluoride intermediates.
Secondary amine substrate	110-89-4	P1506301	Piperidine	AR, ≥99.5%	A classical cyclic secondary amine substrate, suitable for assessing the compatibility of DAST-mediated systems with aliphatic secondary amines in amidation reactions.
Representative fatty acid amide product	1120-16-7	L157748	Lauramide	≥96%(GC)	A representative fatty acid amide product that can correspond to the amidation outcome of fatty acid substrates such as lauric acid, illustrating the direct product value of this route in fatty acid amide preparation.
Representative fatty acid amide product	124-26-5	S161124	Fatty acid amide (Contains C16, C18 amides)	≥90%, Contains C16, C18 amides	A representative mixed long-chain fatty acid amide product that can correspond to the amidation outcomes of long-chain fatty acid substrates such as palmitic acid and stearic acid, illustrating the application of this route in fatty acid amide preparation.
Representative fatty acid amide product	301-02-0	O105240	Oleamide	≥70%	A representative unsaturated long-chain fatty acid amide product that can correspond to the amidation outcome of oleic acid, illustrating a representative application of the DAST route in the preparation of unsaturated fatty acid amides.
Drug-related amide molecule / representative late-stage amidation product	71320-77-9	M118359	Moclobemide (Ro 111163)	Moligand™, ≥98%	A representative amide-containing drug molecule, suitable for illustrating the value of DAST-mediated amidation routes in the construction of drug-related amide scaffolds and in late-stage molecular modification.
Drug-related amide molecule / representative late-stage amidation product	75706-12-6	L129518	Leflunomide	Moligand™, ≥98%	A representative fluorinated drug-like amide molecule, suitable for illustrating the significance of the DAST route in the construction of fluorinated amide scaffolds and in the synthesis of drug-related molecules.
Drug-related amide molecule / representative late-stage amidation product	73-31-4	M118674	Melatonin	Moligand™, ≥98%	A representative bioactive molecule containing an amide bond, suitable for illustrating representative applications of this route in the construction of amide scaffolds relevant to drugs or bioactive molecules.

Table 4 | Traditional Amidation Activation and Acyl Chloride Route Comparison Systems

Category	CAS No.	Aladdin Catalog No.	Name	Specification or Purity	Product Features and Applications
Acyl chloride route comparison activation reagent	79-37-8	O434200	Oxalyl chloride	Reagent grade, high purity, ≥99%	A commonly used reagent for converting carboxylic acids into acyl chlorides; it can serve as a traditional acyl chloride route comparison for the DAST-mediated in situ acyl fluoride formation–amidation route, allowing comparison of activation mode, operational steps, and workup differences.
Acyl chloride route comparison activation reagent	7719-09-7	T433841	Thionyl chloride	High purity, reagent grade, ≥99.5%, low iron	A classical reagent for converting carboxylic acids into acyl chlorides; it can serve as an important comparison activation system for the DAST route, allowing comparison of operational and selectivity differences between in situ acyl fluoride and acyl chloride intermediate routes.
Traditional coupling reagent comparison	530-62-1	C109315	N,N'-Carbonyldiimidazole (CDI)	≥99%	A commonly used carboxylic acid activation reagent that can serve as a non-acyl-chloride comparison system for the DAST route, allowing comparison of room-temperature activation and workup convenience.
Traditional coupling reagent comparison	538-75-0	D106074	N,N′-Dicyclohexylcarbodiimide	≥99%	A classical carboxylic acid coupling reagent that can serve as an important comparison system for the DAST-mediated room-temperature amidation route, allowing comparison of activation mode, byproduct burden, and purification difficulty.
Traditional coupling reagent comparison	693-13-0	N420184	N,N'-Diisopropylcarbodiimide	≥98.5%	A commonly used carbodiimide coupling reagent that can be used to compare the DAST route in terms of operational simplicity and differences in byproduct handling during amidation reactions.
Traditional coupling reagent comparison	25952-53-8	E106172	N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride	≥98%	A water-soluble carbodiimide coupling reagent and one of the commonly used amidation activation systems; it can serve as a practical comparison between the DAST route and traditional coupling-reagent routes.
Traditional coupling reagent comparison	148893-10-1	H109327	HATU	≥99%	A highly efficient coupling reagent commonly used in amidation systems requiring high reactivity; it can serve as a comparison between the DAST route and high-activity coupling-reagent routes.
Traditional coupling reagent comparison	125700-67-6	T109338	TBTU	≥98%	A commonly used uronium-type coupling reagent that can serve as a comparison coupling system for the DAST route, allowing comparison between the classical coupling-reagent method and the in situ acyl fluoride formation method.

Note: The above are representative Aladdin products. For more product specifications, please refer to the product list at the end of the article, or search the Aladdin website using the “product name/CAS/catalog number.”

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