X81175-Tech AL-180.qxd:AL-180.qxd 10/22/07 9:05 AM Page 1 AL-180 Diazald® and Diazomethane Generators AL-180 Diazald® and Diazomethane Generators VI. REFERENCES AND NOTES Table I A LDRICH D IAZOMETHANE G ENERATORS 1) See a precaution published in ref. 12 below, p 945: "Although this material has been kept at room temperature for years with- Technical Bulletin sigma-aldrich.com Cat. No. Description Amount of Diazomethane (mmol) out significant change, there has been reported one instance in which a sample stored for several months detonated sponta- neously. For long periods of storage, it is recommended that the material be recrystallized and placed in a dark bottle." 3050 Spruce Street, St. Louis, MO 63103 ® Z411736 Diazomethane Generator with System 45 connection <1 2) McKay, A.F. J. Am. Chem. Soc. 1948, 70, 1974. Tel.: (800) 521-8956 • (314) 771-5765 Fax: (800) 325-5052 • (314) 771-5757 Z108898 Mini Diazald® Apparatus with Clear-Seal® joints 1-50 3) Registry of Toxic Effects of Chemical Substances; NIOSH: Cincinnati, OH; MF4200000. 4) Mandell, J.D.; Greenberg, J. Biochem. Biophys. Res. Commun. 1960, 3, 575; Adelberg, E.A.; Mandel, M.; Chen, G.C.C. ibid. ® ® Z419761 Diazald Glassware Set with System 45 connections 1-100 1965, 18, 788. Diazald® and Diazomethane Generators Z108510 Macro Diazald® Kit with Clear-Seal® joints 200-300 5) Pizey, J.S. In Synthetic Reactions, Halsted: New York, 1974; Vol. II, Chapter 4. 6) Hopps, H.B. Aldrichimica Acta 1970, 3(4), 9. 7) Black, T.H. Aldrichimica 1983, 16(1), 3 (reprint available on request). WARNING! 8) Gutsche, C.D. In Organic Reactions; Adams, R., Ed.; John Wiley & Sons: New York, 1954; Vol. VIII, p 392. Because of the highly toxic and explosive nature of diazomethane, all reactions involving its preparation and use 9) Registry of Toxic Effects of Chemical Substances; NIOSH: Cincinnati, OH; PA 7000000. should be carried out in an efficient chemical fume hood and behind a safety shield. Avoid use of PVC tubing or ® 10) Lewis, C.E. Occup. Med. 1964, 6, 91. Table II CONTENTS OF DEUTERO-DIAZALD PREP SET other plastic tubings with Diazald® kits. 11) Schoental, R. Nature 1960, 188, 420. Cat. No. Reagent Quantity (g) 12) De Boer, T.J.; Backer, H.J. In Organic Synthesis, Collective Volume IV, Rabjohn, N., Ed.; John Wiley & Sons: New York, 1963; p 250. I. DIAZALD® II. DIAZOMETHANE D28000 Diazald® 30 13) Fales, H.M.; Jaouni, T.M.; Babashak, J.F. Anal. Chem. 1973, 43, 2302. Reprinted with permission . Copyright by the American Chemical Society. Diazald® (N-methyl-N-nitroso-p-toluenesulfonamide) is the 1. Properties and application 164488 Sodium deuteroxide, 30wt % solution in D O20 2 14) Hudlicky, M. J. Org. Chem. 1980, 45, 5377. This reference contains experimental procedures. reagent of choice for the preparation of diazomethane in 15) Hudlicky, M. J. Org. Prep. Proced. Int. 1982, 14, 354. 164496 2- (2-Ethoxyethoxy)ethan(ol-d), 97 atom % D 50 quantities greater than one millimole. Diazomethane (CH2N2) is a gas at room temperature, liquifies at 16) Campbell, J.R. Chem. Ind. 1972, 540. -23 °C (density 1.45), and freezes at -145 °C. It is the most common 151882 Deuterium oxide, 99.9 atom % D 25 17) Arndt, F. In Organic Syntheses, Collective Volume II, Blatt, A.H., Ed.; John Wiley & Sons: New York, 1943; p 165. 1. Properties methylating reagent for carboxylic acids and has found wide 18) De Boer, T.J.; Backer, H.J. In Organic Syntheses, Collective Volume IV, Rabjohn, N., Ed.; John Wiley & Sons: New York, 1963; application in the methylation of phenols, enols, and hetero- p 225. O Molecular formula C8H10N2O3S atoms such as nitrogen and sulfur. The preparation and reactions 19) House, H.O.; Grubbs, E.J.; Cannon, W.F. J. Am. Chem. Soc. 1960, 82, 4099. Me S NMe Formula weight 214.24 of diazomethane have been reviewed.5-7 20) Cram, D.J.; Helgersen, R.C. J. Am. Chem. Soc. 1966, 88, 3515. O NO Table III RATIOS OF REAGENTS TO DIAZOMETHANE-d2 m.p. 61-62 °C 21) Bachmann, W.E.; Struve, W.S. In Organic Reactions, Adams, R., Ed.; John Wiley & Sons: New York, 1942; p 50. Appearance yellow powder 2. Toxicity and hazards Diazald® 2(2-Ethoxyethoxy)(ethan(ol-d)) 30% NaOD CD N (mmol) Atom 22) Bradamante, S.; Maiorana, S.; Mangia, A.; Pazani, G. Tetrahedron Lett. 1969, 2871. 2 2 23) Ngan, F.; Toofan, M., J. Chrom. Sci. 1991, 29, 8. (g) (g) (g) produced % D Cat. No. D2,800-0 Although diazomethane can be handled safely as a dilute Fieser 1, 191, 2, 102 solution in an inert solvent, it presents several safety hazards. It 5.0 50 20 12 97 Aldrich is a registered trademark of Sigma-Aldrich Biotechnology LP and Sigma-Aldrich Co. Merck Index 139621 is extremely toxic8 and highly irritating,9 causing pulmonary 10.0 50 20 24 93 System 45® is a registered trademark of NDS Technologies, Inc. RTECS# XT5950000 edema when inhaled in high concentrations. Long-term, low- 15.0 50 20 36 92 Diazald® is a registered trademark of Sigma-Aldrich Co. level exposure may lead to sensitization, resulting in asthma- 2. Toxicity, storage, and stability 10 ® like symptoms. In addition, diazomethane has been cited as 20.0 50 20 48 88 Clear-Seal is a registered trademark of Wheaton 9-11 ® a carcinogen. ® Diazald is a severe skin irritant and all skin contact should be 21.4 50 20 50 87 Viton is a registered trademark of du Pont Dow Elastomers avoided. The material should be stored in a brown bottle at room Diazomethane has been known to explode unaccountably, temperature. It is stable at room temperature for at least one both as a gas and in solution. Rough surfaces are proven ini- ORDERING INFORMATION 1 year; however, we recommend that the material be kept refrig- tiators of detonations. De Boer and Backer12 reported that an Telephone: 800-558-9160 Fax: 800-962-9591 erated for prolonged storage. explosion of diazomethane had been observed at the moment International: 414-273-3850 International: 414-273-4979 of crystal formation from a supersaturated solution. Aldrich mailing address: Dioxane and other solvents that may freeze should not be Techware used as the sharp edges of crystals formed may cause an P.O. Box 2060 explosion. Milwaukee, WI 53201 USA World Headquarters Order/Customer Service (800) 325-3010 • Fax (800) 325-5052 3050 Spruce St., St. Louis, MO 63103 (314) 771-5765 Technical Service (800) 325-5832 • sigma-aldrich.com/techservice sigma-aldrich.com Development/Bulk Manufacturing Inquiries (800) 244-1173 ©2007 Sigma-Aldrich Co. All rights reserved. SIGMA, , SAFC, , SIGMA-ALDRICH, ALDRICH, , FLUKA, , and SUPELCO, are trademarks belonging to Sigma-Aldrich Co. and its affiliate Sigma-Aldrich Biotechnology, L.P. Sigma brand products are sold through Sigma-Aldrich, Inc. Sigma-Aldrich, Inc. warrants that its products conform to the information contained in this and other Sigma-Aldrich publications. Purchaser must determine the suitability of the product(s) for their particular use. Additional terms and conditions may apply. Please see reverse side of the invoice or packing slip. 03517-504500 Printed on Recycled Paper — 0107 A Worldwide Operation with a Global Commitment X81175-Tech AL-180.qxd:AL-180.qxd 10/22/07 9:05 AM Page 1 AL-180 Diazald® and Diazomethane Generators AL-180 Diazald® and Diazomethane Generators VI. REFERENCES AND NOTES Table I A LDRICH D IAZOMETHANE G ENERATORS 1) See a precaution published in ref. 12 below, p 945: "Although this material has been kept at room temperature for years with- Technical Bulletin sigma-aldrich.com Cat. No. Description Amount of Diazomethane (mmol) out significant change, there has been reported one instance in which a sample stored for several months detonated sponta- neously. For long periods of storage, it is recommended that the material be recrystallized and placed in a dark bottle." 3050 Spruce Street, St. Louis, MO 63103 ® Z411736 Diazomethane Generator with System 45 connection <1 2) McKay, A.F. J. Am. Chem. Soc. 1948, 70, 1974. Tel.: (800) 521-8956 • (314) 771-5765 Fax: (800) 325-5052 • (314) 771-5757 Z108898 Mini Diazald® Apparatus with Clear-Seal® joints 1-50 3) Registry of Toxic Effects of Chemical Substances; NIOSH: Cincinnati, OH; MF4200000. 4) Mandell, J.D.; Greenberg, J. Biochem. Biophys. Res. Commun. 1960, 3, 575; Adelberg, E.A.; Mandel, M.; Chen, G.C.C. ibid. ® ® Z419761 Diazald Glassware Set with System 45 connections 1-100 1965, 18, 788. Diazald® and Diazomethane Generators Z108510 Macro Diazald® Kit with Clear-Seal® joints 200-300 5) Pizey, J.S. In Synthetic Reactions, Halsted: New York, 1974; Vol. II, Chapter 4. 6) Hopps, H.B. Aldrichimica Acta 1970, 3(4), 9. 7) Black, T.H. Aldrichimica 1983, 16(1), 3 (reprint available on request). WARNING! 8) Gutsche, C.D. In Organic Reactions; Adams, R., Ed.; John Wiley & Sons: New York, 1954; Vol. VIII, p 392. Because of the highly toxic and explosive nature of diazomethane, all reactions involving its preparation and use 9) Registry of Toxic Effects of Chemical Substances; NIOSH: Cincinnati, OH; PA 7000000. should be carried out in an efficient chemical fume hood and behind a safety shield. Avoid use of PVC tubing or ® 10) Lewis, C.E. Occup. Med. 1964, 6, 91. Table II CONTENTS OF DEUTERO-DIAZALD PREP SET other plastic tubings with Diazald® kits. 11) Schoental, R. Nature 1960, 188, 420. Cat. No. Reagent Quantity (g) 12) De Boer, T.J.; Backer, H.J. In Organic Synthesis, Collective Volume IV, Rabjohn, N., Ed.; John Wiley & Sons: New York, 1963; p 250. I.