The Trifluoromethylating Sandmeyer Reaction: A Method for Transforming CN into CCF<sub>3</sub>

Browne, Duncan L.

doi:10.1002/anie.201308997

Cited by 55 publications

(14 citation statements)

References 23 publications

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“…[17][18][19][20][21][22] Diazo compounds are also important 1,3-dipoles for heterocycle-forming cycloaddition reactions. [23][24][25][26][27][28] The diazonium ion moiety is an important leaving group in Sandmeyer, [29][30][31] Meerwein, [32,33] Balz-Schiemann [34,35] and palladium-catalysed cross coupling [36][37][38] chemistry; it is also an essential reagent for the preparation of azo compounds, the backbone of the synthetic dye industry. [38,39] The versatility of the diazo and diazonium moieties is matched only by their fearsome reputation.…”

Section: Introductionmentioning

confidence: 99%

“…Diazo compounds are also important 1,3‐dipoles for heterocycle‐forming cycloaddition reactions 23–28. The diazonium ion moiety is an important leaving group in Sandmeyer,29–31 Meerwein,32, 33 Balz–Schiemann34, 35 and palladium‐catalysed cross coupling36–38 chemistry; it is also an essential reagent for the preparation of azo compounds, the backbone of the synthetic dye industry 38. 39…”

Section: Introductionmentioning

confidence: 99%

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Taming Hazardous Chemistry in Flow: The Continuous Processing of Diazo and Diazonium Compounds

Deadman

Collins

Maguire

2014

Chemistry A European J

178

104

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Type of publicationArticle ( 1 This is the pre-peer reviewed version of the following article: Deadman, B. J., Benjamin J. Deadman, [a] Stuart G. Collins [a] and Anita R. Maguire* [b] 2 This is the pre-peer reviewed version of the following article: Deadman, B. J., , Taming Hazardous Chemistry in Flow: The Continuous Processing of Diazo and Diazonium Compounds. Chem. Eur. J. which has been published in final form at http://dx.doi.org/10.1002/chem.201404348 DOI: 10.1002/chem.201404348 IntroductionDiazo and diazonium compounds are extremely versatile intermediates and reagents in organic synthesis. Diazoalkanes are important alkylating reagents, [1,2] while α-diazocarbonyls are important for their role in generating carbenes and metal carbenoids, [1,[3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and also for providing access to reactive ketene and heteroanalogous intermediates via the Wolff rearrangement. [21][22][23][24][25][26] Diazo compounds are also important 1,3-dipoles for heterocycle-forming cycloaddition reactions. [27][28][29][30][31][32] The diazonium ion moiety is an important leaving group in Sandmeyer, [33][34][35] Meerwein, [36,37] Balz-Schiemann [38,39] and palladium catalysed cross coupling [40][41][42] chemistry; and is an essential reagent for the preparation of azo compounds, the backbone of the synthetic dye industry. [42,43] The versatility of the diazo and diazonium moieties is matched only by their fearsome reputation. Diazoalkanes are highly toxic due to their potent alkylation of DNA. [44] Furthermore, diazo and diazonium compounds are highly energetic by nature and explosions can be triggered by shock, heat or exposure to concentrated acids. [44,45] α-Diazocarbonyls are considerably more stable than diazoalkanes and diazoniums due to the resonance stabilisation of adjacent carbonyls but detonation is still possible under more forcing conditions. [44,46] These safety concerns necessitate caution when using diazo and diazonium intermediates in the laboratory, and have limited their use on scale in industry. The synthetic utility of these hazardous compounds has led to a recent interest in developing safer alternative methods for their preparation and use. [1,44] Continuous processing is rapidly growing in the academic, pharmaceutical and fine chemical sectors due to its favourable safety profile among other benefits such as efficient mixing, enhanced heat and mass transfer, access to extreme reaction conditions, reproducibility and scale up, in-line workups and automated operation. [47][48][49][50][51][52][53][54] The safety profile offered by continuous processing is perhaps the most compelling reason for its popularity in recent years. Sensitive and toxic reaction intermediates can be generated and consumed during a single flow process without the need for stockpiling hazardous quantities of material. Furthermore, the high surface area-tovolume ratio of tubular flow reactors also ensures rapid dissipation of heat and reduces the risk of reaction runaway.Continuou...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Taming Hazardous Chemistry in Flow: The Continuous Processing of Diazo and Diazonium Compounds

Deadman

Collins

Maguire

2014

Chemistry A European J

178

104

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“… 44 Based on radical trapping experiments, 39 it is generally presumed that this type of Sandmeyer reaction proceeds through a radical pathway. 45 In this study, the diazotization of the primary aromatic amine, followed by the dissociation of the diazonium species (I), may yield a radical intermediate (II). This intermediate may undergo oxidative addition with [ 11 C]CuCF 3 to produce an unstable [ 11 C]CuCF 3 -aryl adduct (III), which is then subject to reductive elimination yielding the desired [ 11 C]trifluoromethylarene ( Scheme 4 ).…”

Section: Resultsmentioning

confidence: 94%

Rapid and Efficient Synthesis of [¹¹C]Trifluoromethylarenes from Primary Aromatic Amines and [¹¹C]CuCF₃

2020

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Prior studies have shown that trifluoromethylarenes can be labeled in high molar activities ( A m > 200 GBq/μmol) with positron-emitting carbon-11 ( t 1/2 = 20.4 min) by the reaction of the copper(I) derivative of [ 11 C]fluoroform [ 11 C]CuCF 3 , with several types of precursors, such as aryl iodides, arylboronic acids, and aryldiazonium salts. Nonetheless, these precursors can be challenging to synthesize, and in the case of diazonium salts, are unstable. Methods that reduce challenges in precursor preparation for the synthesis of [ 11 C]trifluoromethylarenes are desirable to enhance possibilities for developing biologically relevant 11 C-labeled compounds as radiotracers for biomedical imaging with positron emission tomography (PET). Here, we explored the production of no-carrier-added [ 11 C]trifluoromethylarenes from commercially available primary aromatic amines through reactions of [ 11 C]CuCF 3 with diazonium salts that were generated in situ . Moderate to high isolated decay-corrected radiochemical yields (RCY) (32–84%) were obtained rapidly (within 2 min) for many para-substituted and meta-substituted primary aromatic amines bearing a halo, methoxy, thiomethyl, hydroxy, nitro, nitrile, carboxyl, ethylcarboxy, or trifluoromethyl substituent. Null to low RCYs (0–13%) were observed only for ortho bromo-, nitro-, or nitrile-substituted precursors. This new radiosynthetic method usefully expands options for producing PET radiotracers bearing a [ 11 C]trifluoromethyl group, especially from aryl amine precursors.

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“…The advantage of the Wang and Fu protocols is that they give high yields even if the diazotization is performed in situ . D. L. Browne, who compared the three protocols in a highlight article, views Fu’s method as the most straightforward for this reason 30. However, it is based on the exceedingly expensive Umemoto reagent (47 €/mmol)31 and calls for overstoichiometric amounts of copper.…”

Section: Methodsmentioning

confidence: 99%

One‐Pot Sandmeyer Trifluoromethylation and Trifluoromethylthiolation

et al. 2014

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Practical one-pot procedures were developed for both Sandmeyer-type trifluoromethylations and trifluoromethylthiolations. Starting from broadly available (hetero)aromatic amines, various benzotrifluorides were synthesized in high yields via in situ diazotization and copper-mediated trifluoromethylation using the inexpensive Ruppert-Prakash trifluoromethylating reagent. In the presence of sodium thiocyanate as a sulfur source, aryl trifluoromethyl thioethers are exclusively formed.

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The Trifluoromethylating Sandmeyer Reaction: A Method for Transforming CN into CCF₃

Cited by 55 publications

References 23 publications

Taming Hazardous Chemistry in Flow: The Continuous Processing of Diazo and Diazonium Compounds

Taming Hazardous Chemistry in Flow: The Continuous Processing of Diazo and Diazonium Compounds

Rapid and Efficient Synthesis of [¹¹C]Trifluoromethylarenes from Primary Aromatic Amines and [¹¹C]CuCF₃

One‐Pot Sandmeyer Trifluoromethylation and Trifluoromethylthiolation

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The Trifluoromethylating Sandmeyer Reaction: A Method for Transforming CN into CCF3

Cited by 55 publications

References 23 publications

Taming Hazardous Chemistry in Flow: The Continuous Processing of Diazo and Diazonium Compounds

Taming Hazardous Chemistry in Flow: The Continuous Processing of Diazo and Diazonium Compounds

Rapid and Efficient Synthesis of [11C]Trifluoromethylarenes from Primary Aromatic Amines and [11C]CuCF3

One‐Pot Sandmeyer Trifluoromethylation and Trifluoromethylthiolation

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The Trifluoromethylating Sandmeyer Reaction: A Method for Transforming CN into CCF₃

Rapid and Efficient Synthesis of [¹¹C]Trifluoromethylarenes from Primary Aromatic Amines and [¹¹C]CuCF₃