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 Organics - Perchlorates in Organic Synthesis
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LiClO4 and Mg(ClO4)2 Show Dramatic Results
Chemists are unaccustomed to using the words "perchlorates" and "organics" in the same sentence, much less include them in the same chemical reaction or as components in a commercial product (e.g. battery electrolyte solutions). However, the risk vs. benefit equation for such technologies has undergone a significant shift in just the last few years. The development of novel chemistries promoted by anhydrous perchlorate salts in organic media has accelerated to the point that closer examination of both chemical and physical properties of these systems is imperative, (see J. R. Long, Perchlorates in Organic Media, G.l.T. Laboratory Journal, 2000, 4, 222, reprints available from GFS).
Recent chemical literature describes a growing arsenal of synthetic methodologies involving lithium and magnesium perchlorates [see Sankararaman and Nesakumar, Eur. J. Org. Chem. 2000; P. Grieco, Aldrichimica Acta 1991, 24, 59]. These reagents, especially lithium perchlorate in diethyl ether (LPDE), have been shown to dramatically affect yield, selectivity, rate and/or reaction conditions for Diels-Alder reactions, Michael additions, Friedel-Crafts acylations, and a wide range of condensations, inter- and intra-molecular rearrangements. The prospect of improving synthetic routes or developing unconventional strategies for constructing novel molecular frameworks is too appealing to ignore.
The key to much of this behavior has been attributed to the uncommon solubility of anhydrous LiClO4 in diethyl ether: 113 grams per 100 grams of solvent (well over 5M); in turn, the contrasting insolubility (less than one gram per 100) of the trihydrate salt of lithium perchlorate is not surprising. What is surprising, however, is the fact that magnesium perchlorate also promotes an impressive array of organic transformations despite its limited solubility in ether (<0.1 gram per 100 grams solvent). Despite some concerns about perchlorate safety, research in this area of chemistry has proceeded vigorously.
One area where these chemistries have yet to be exploited is in process chemistry and pilot plant scale development. This is understandable in light of concerns relating to the use of diethyl ether. However, several innovative chemistries have been explored which promise to enhance the appeal of perchlorate-promoted synthetic methodologies. Use of lithium perchlorate on an inert medium such as silica gel is one possibility. Other solvent systems or mixtures may also show promise, and the potential application to synthetic problem-solving is considerable.
Since the prospect of clarifying the behavior of perchlorate salts in larger scale organic systems is not very appealing to the research community, GFS Chemicals is committed to a program that will generate and disseminate a wide range of technical and safety data in this area. Adiabatic calorimetry has provided some interesting insights (question 27, previous section). In addition, GFS has used the 5M LPDE reagent to run multi-molar scale reactions between isoprene and maleic anhydride; the reactions ran smoothly, but additional tests remain to be run to better understand issues pertaining to the isolation and reclamation of the lithium perchlorate salt.
The advantages of these methodologies are obvious:
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Perchlorate salts promote chemistries that are not possible with other reagents
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Dramatic improvement of reaction rates and selectivities are common
-
Chemistries of interest can be developed apart from the LPDE reaction medium
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The concept of "naked ion" Li+ chemistries in organic media has broad synthetic implications
GFS publication #495 – Practical Use of Anhydrous LiClO4 and Mg(ClO4)2 in Organic Synthesis – was compiled to provide a concise summary of the most novel and dramatic synthetic uses of these reagents. Over 20 reaction categories are represented in its 44 pages, as well as a comprehensive introduction to the physical and chemical properties of perchlorates, plus insights on safety and larger scale use of perchlorates in organic media.
Each reaction type represented includes reaction schemes, a brief description of reaction features, and appropriate references; a total of over 200 references are provided. This monograph can be obtained at no charge by calling the GFS order department, and is available at the GFS booth during major ACS meetings and trade shows. In addition, technical updates will regularly be provided on the GFS web site as new research reports are published.
It is most fitting that one of the earliest topics of interest to the company founder, Prof. G. Frederick Smith, was the behavior of perchlorate salts in organic solvents. The remarkable solubility (>6M) of anhydrous lithium perchlorate in diethyl ether was an indicator of unusual chemistries to come – it just took upwards of 70 years to see the broader development of its potential.
GFS will continue to explore the commercialization of these chemistries. Please
contact us if you have a problem with a synthetic pathway, a difficult target molecule, or issues relating to reaction conditions or process scale up that might benefit from these novel perchlorate chemistries. One solution may be the possibility of having us carry out some synthetic transformation that you'd prefer not to do in your facility. We'd be happy to discuss matters such as these with you in strictest confidence. www.development@gfschemicals.com.
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Organics - Perchlorates in Organic Synthesis
LiClO4 and Mg(ClO4)2 Show Dramatic Results
Chemists are unaccustomed to using the words "perchlorates" and "organics" in the same sentence, much less include them in the same chemical reaction or as components in a commercial product (e.g. battery electrolyte solutions). However, the risk vs. benefit equation for such technologies has undergone a significant shift in just the last few years. The development of novel chemistries promoted by anhydrous perchlorate salts in organic media has accelerated to the point that closer examination of both chemical and physical properties of these systems is imperative, (see J. R. Long, Perchlorates in Organic Media, G.l.T. Laboratory Journal, 2000, 4, 222, reprints available from GFS).
Recent chemical literature describes a growing arsenal of synthetic methodologies involving lithium and magnesium perchlorates [see Sankararaman and Nesakumar, Eur. J. Org. Chem. 2000; P. Grieco, Aldrichimica Acta 1991, 24, 59]. These reagents, especially lithium perchlorate in diethyl ether (LPDE), have been shown to dramatically affect yield, selectivity, rate and/or reaction conditions for Diels-Alder reactions, Michael additions, Friedel-Crafts acylations, and a wide range of condensations, inter- and intra-molecular rearrangements. The prospect of improving synthetic routes or developing unconventional strategies for constructing novel molecular frameworks is too appealing to ignore.
The key to much of this behavior has been attributed to the uncommon solubility of anhydrous LiClO4 in diethyl ether: 113 grams per 100 grams of solvent (well over 5M); in turn, the contrasting insolubility (less than one gram per 100) of the trihydrate salt of lithium perchlorate is not surprising. What is surprising, however, is the fact that magnesium perchlorate also promotes an impressive array of organic transformations despite its limited solubility in ether (<0.1 gram per 100 grams solvent). Despite some concerns about perchlorate safety, research in this area of chemistry has proceeded vigorously.
One area where these chemistries have yet to be exploited is in process chemistry and pilot plant scale development. This is understandable in light of concerns relating to the use of diethyl ether. However, several innovative chemistries have been explored which promise to enhance the appeal of perchlorate-promoted synthetic methodologies. Use of lithium perchlorate on an inert medium such as silica gel is one possibility. Other solvent systems or mixtures may also show promise, and the potential application to synthetic problem-solving is considerable.
Since the prospect of clarifying the behavior of perchlorate salts in larger scale organic systems is not very appealing to the research community, GFS Chemicals is committed to a program that will generate and disseminate a wide range of technical and safety data in this area. Adiabatic calorimetry has provided some interesting insights (question 27, previous section). In addition, GFS has used the 5M LPDE reagent to run multi-molar scale reactions between isoprene and maleic anhydride; the reactions ran smoothly, but additional tests remain to be run to better understand issues pertaining to the isolation and reclamation of the lithium perchlorate salt.
The advantages of these methodologies are obvious:
·
-
Perchlorate salts promote chemistries that are not possible with other reagents
-
Dramatic improvement of reaction rates and selectivities are common
-
Chemistries of interest can be developed apart from the LPDE reaction medium
-
The concept of "naked ion" Li+ chemistries in organic media has broad synthetic implications
GFS publication #495 – Practical Use of Anhydrous LiClO4 and Mg(ClO4)2 in Organic Synthesis – was compiled to provide a concise summary of the most novel and dramatic synthetic uses of these reagents. Over 20 reaction categories are represented in its 44 pages, as well as a comprehensive introduction to the physical and chemical properties of perchlorates, plus insights on safety and larger scale use of perchlorates in organic media.
Each reaction type represented includes reaction schemes, a brief description of reaction features, and appropriate references; a total of over 200 references are provided. This monograph can be obtained at no charge by calling the GFS order department, and is available at the GFS booth during major ACS meetings and trade shows. In addition, technical updates will regularly be provided on the GFS web site as new research reports are published.
It is most fitting that one of the earliest topics of interest to the company founder, Prof. G. Frederick Smith, was the behavior of perchlorate salts in organic solvents. The remarkable solubility (>6M) of anhydrous lithium perchlorate in diethyl ether was an indicator of unusual chemistries to come – it just took upwards of 70 years to see the broader development of its potential.
GFS will continue to explore the commercialization of these chemistries. Please
contact us if you have a problem with a synthetic pathway, a difficult target molecule, or issues relating to reaction conditions or process scale up that might benefit from these novel perchlorate chemistries. One solution may be the possibility of having us carry out some synthetic transformation that you'd prefer not to do in your facility. We'd be happy to discuss matters such as these with you in strictest confidence. www.development@gfschemicals.com.
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