Honors Cup Synthetic ProposalExpected yield: 61% , 8.6 gExpected yield: 54 %, 1.1475 gExpected yield: 60 %, .514 gHonors Cup Synthetic ProposalSection: 211Group Members: Andrew Brod, Jamie (Brian) Magnuson, Nizar TakiTitle: Synthesis of 5-Amino-1,3-dimethylurcil (Precursor to Caffeine)Introduction: (what makes your target interesting?)Although caffeine occurs naturally in at least sixty-three different plant species, it has been manufactured and used because of its unique effects on our bodies. It is found mainly in beverages, but is also used in several types of prescription medications, diuretics, and pain relievers. Caffeine is sought by many for its abilities to increase alertness and energy. As energy drinks such as Red Bull ™ and Amp ™ become more and more popular, caffeine continues to stretch its influence. 5-Amino-1,3-dimethylurcil is a precursor to caffeine and has many of the same functional groups. Here we produce it in a three-step synthesis.Overall synthetic reaction scheme: (a Chemdraw or similar drawing of all three steps)HNNHOONNOOCH3H3CNNOOCH3H3C NO2NNOOCH3H3C NH2Ura cil1,3-dimethylura cil1,3- dime thyl-5-nitrouracil5-a mino-1,3-dimethylura cilN aHDM SO ,CH3IHNO3H2SO4Fe/HCl1Step 1Synthetic transformation 1: (Chemdraw picture of first transformation)Experimental 1 (notes if this transformation is not exactly the one reported in literature (e.g. on a different scale) and how it was modified):- 6.0 g (.053 mol) of uracil were stirred for a week (changed from “overnight”) in 300 mL of DMSO at room temperature.- 5.1 g (.265 mol) of sodium hydride were added carefully to the solution of uracil.- 37.6 g (.265 mol) of methyl iodide were added slowly over a period of ten minutes.- The mixture was stirred for forty minutes and then diluted with 100 mL of water to remove excess of hydride.- Concentrated HCl was added to the solution until it reached a pH of 1-2.- The product was then extracted with methylene chloride and washed with saturated bicarbonate solution until neutral.- After removing the dichloromethane, 1,3-dimethyl-uracil should be left behind.- HNMR peaks: 3.29 (s, 3H), 3.37 (s, 3H), 5.65 (d, J = 15 Hz, 1H, HC=), 7.1 (d, J = 15 Hz,1H, HC=)Notes:- The reaction mixture was stirred for a week instead of overnight because we cannot cometo lab every day (it’s a darn shame…).Expected yield: 61% , 8.6 gSafety, disposal and green issues 1:Uracil- Minimize contactSodium Hydride (NaH)- Reacts violently with water- Incompatible with water, acids, alcohols, and strong oxidizing agents- Dispose of correctly2HNNHOONNOOCH3H3CUra cil1,3-dim ethylura cilNa HDMS O,CH3IMethyl Sulfoxide (DMSO)- Harmful in inhaledMethyl Iodide (CH3I)- Fatal if inhaled or absorbed through skin- Highly toxic- May cause cancerStep 2Synthetic transformation 2: (Chemdraw picture of second transformation)NNOOCH3H3CNNOOCH3H3C NO21,3-dim ethylura cil1,3-dim ethyl-5-nitrour acilHNO3H2SO4Experimental 2 (notes if this transformation is not exactly the one reported in literature (e.g. on a different scale) and how it was modified):- 1.6 g (.0114 mol) of 1,3-Dimethyl-5-nitrouracil were added carefully to a mixture of 1.2 mL of fuming nitric acid and 1.2 mL of concenetrated sulfuric acid and stirred carefully for thirty minutes at room temperature.- The solution was refluxed for an hour.- The solution was then added carefully to 6 mL of ice cold water.- The light yellow colored crystals were filtered and washed with ice water- M.p.: 121-122 C, IR (mull): 1720, 1675.Notes:- Reaction ingredients were scaled up by a factor of two to obtain the target .5 grams of productExpected yield: 54 %, 1.1475 gSafety, disposal and green issues 2:1,3-Dimethyluracil- Minimize contact3Nitric Acid (HNO3)- Corrosive, may cause fire- May be fatal if inhaled- Use adequate ventilationSulfuric Acid (H2SO4)- Reacts violently with water and metals- Avoid inhalation or other contact- Causes severe burns, may be carcinogenicStep 3 Synthetic transformation 3: (Chemdraw picture of third transformation)Experimental 3 (notes if this transformation is not exactly the one reported in literature (e.g. on a different scale) and how it was modified):- One gram (.0054 mol) of 1,3-Dimethyl-5-nitrouracil was dissolved in 2.7 mL THF (forming a 2M solution). Another 2.7 mL of 1 M HCl was added followed by 3.04 g of active iron powder. - The solution was refluxed for thirty minutes and then neutralized with saturated bicarbonate solution.- The reduced product was extracted into methylene chloride and purified using flash chromatography on silica gel using ethyl acetate.- The product was then characterized by IR and NMR.- IR (mull): 3400 (W), 1725, 1665. HNMR: 3.45 (s, 3H), 3.75 (s, 3H), 5.6 (s, 1H), 9 (s, 1H)Notes- Reaction ingredients were scaled up by a factor of two to obtain the target .5 grams of productExpected yield: 60 %, .514 gSafety, disposal and green issues 3:4NNOOCH3H3C NO2NNOOCH3H3C NH21,3- dimethyl-5-nitroura cil5-a mino-1,3-dim ethyluracilFe/HC l1,3-dimethyl-5-nitro-uracil- Minimize contactIron (Fe)- Dust harmful if inhaledHydrochloric acid (HCl)- Very corrosive- Inhalation of vapor dangerous- Causes severe damage to skin- Dangerous for environmentMethylene Chloride (CH2Cl2)- Harmful if swallowed or inhaled- Avoid skin contact- Possible carcinogen and mutagen Overall budget:Chemical Supplier Cost Amt. Needed TotalUracil Pfaltz & Bauer $60.90/25 g 6.0 g $14.62NaH Pfaltz & Bauer $61.95/100 g 5.1 g $3.16DMSO EMD Biosciences$23.00/100 mL 300 mL $69.00CH3I Pfaltz & Bauer $128.10/100 g 37.6 g $48.17HNO3Pfaltz & Bauer $54.85/PT 1.2 mL $0.14H2SO4Pfaltz & Bauer $50.40/500 mL >1.2 mL >$0.12Fe Pfaltz & Bauer $86.10/500 g 3.04 g $0.52Total costs per synthesis: ___$135.622___References (include at least two different sources for your experimentals):Hartley, Jack. “Caffeine and Sports Performance.” Vanderbilt University, 6 February 2004 <http://www.vanderbilt.edu/AnS/psychology/health_psychology/caffeine_sports.htm>.Kowal, M. G.; Narayan, S.; Zajac, M. A.; Zakrzewski, A. G. Synth. Comm. 2003, 33, 3291-3297.Song, Q. H.; Hei, X.; Xu, Z.; Zhang, X.; Guo, Q. Bioorg. Chem. 2003, 31, 357-366.5Itahara, T.; Ebihara, R.; Kawasaki, K. Bulletin Chem. Soc. Japan 1893, 56, 2171-2172.Pecorari, P.; Vampa, G.; Albasini, A.; Rinaldi, M.; Melegari, M.; Costi, M. P. Farmaco. Edizione Scientifica 1988, 43,
View Full Document
Unlocking...