Direct Amidation of carboxylic acids using a Borate Ester Answer ...
Direct Amidation of carboxylic acids using a Borate Ester Answer Sheet
1. Calculate the Atom Economy of the reaction 𝐴𝑡𝑜𝑚 𝐸𝑐𝑜𝑛𝑜𝑚𝑦 (𝐴𝐸 ) =
𝑀𝑊 𝑜𝑓 𝑝𝑟𝑜𝑑𝑢𝑐𝑡(𝑠) × 100% 𝑀𝑊 𝑜𝑓 𝑎𝑙𝑙 𝑟𝑒𝑎𝑐𝑡𝑎𝑛𝑡𝑠
𝐴𝑡𝑜𝑚 𝐸𝑐𝑜𝑛𝑜𝑚𝑦 (𝐴𝐸 ) =
225.29 × 100% 136.15 + 107.16
𝐴𝑡𝑜𝑚 𝐸𝑐𝑜𝑛𝑜𝑚𝑦 (𝐴𝐸 ) =
225.29 × 100% 243.31
𝐴𝑡𝑜𝑚 𝐸𝑐𝑜𝑛𝑜𝑚𝑦 (𝐴𝐸 ) = 92.6%
2. Calculate the Reaction Mass Efficiency (RME) of the reaction
𝑅𝑀𝐸 =
𝑚𝑎𝑠𝑠 𝑜𝑓 𝑖𝑠𝑜𝑙𝑎𝑡𝑒𝑑 𝑝𝑟𝑜𝑑𝑢𝑐𝑡 × 100% 𝑡𝑜𝑡𝑎𝑙 𝑚𝑎𝑠𝑠 𝑜𝑓 𝑟𝑒𝑎𝑐𝑡𝑎𝑛𝑡𝑠
𝑅𝑀𝐸 =
0.41 × 100% 0.27 + 0.21
𝑅𝑀𝐸 =
0.41 × 100% 0.48
𝑅𝑀𝐸 = 85.4%
3. Calculate the Mass Intensity (MI) of the reaction
𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 (𝑀𝐼) =
𝑡𝑜𝑡𝑎𝑙 𝑚𝑎𝑠𝑠 𝑖𝑛 𝑎 𝑝𝑟𝑜𝑐𝑒𝑠𝑠 𝑜𝑟 𝑝𝑟𝑜𝑐𝑒𝑠𝑠 𝑠𝑡𝑒𝑝 𝑚𝑎𝑠𝑠 𝑜𝑓 𝑝𝑟𝑜𝑑𝑢𝑐𝑡
𝑀𝑎𝑠𝑠 = 𝐷𝑒𝑛𝑠𝑖𝑡𝑦 × 𝑉𝑜𝑙𝑢𝑚𝑒 𝑀𝑎𝑠𝑠 (𝑀𝑒𝐶𝑁) = 0.786 × 4 = 3.14𝑔 𝑀𝑎𝑠𝑠 (𝐷𝐶𝑀) = 1.33 × 30 = 39.9𝑔 𝑀𝑎𝑠𝑠 (1𝑀 𝑁𝑎𝐻𝐶𝑂3) = 1.1 × 20 = 22𝑔 𝑀𝑎𝑠𝑠 (1𝑀 𝐻𝐶𝑙 ) = 1.017 × 20 = 20.34𝑔
𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 (𝑀𝐼) =
0.27 + 0.21 + 1.09 + 3.14 + 39.9 + 22 + 20.34 + 2 0.41
𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 (𝑀𝐼) =
88.95 0.41
𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 (𝑀𝐼) = 217
4. What conclusions can you draw about the efficiency of the reaction from these calculations? For example:
Atom Economy is high – almost all of the atoms of the reactants are incorporated into the product AE is approximately equal to RME, good efficiency, no excess of reactants used MI not as good and this is mainly due to the work-up procedure (although MI would have been a lot higher if for example chromatography had been used for purification)
NB These calculations do not show that 2 equiv of a reagent (the borate ester) are being used– swamped in MI calculation due to the work-up, not included in RME. Also these calculations do not tell us anything about other parameters – i.e. the ‘bigger picture’
5. What proportion of the Mass Intensity is attributable to the work-up procedure? 𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 𝑤𝑜𝑟𝑘 − 𝑢𝑝 (𝑀𝐼) =
𝑡𝑜𝑡𝑎𝑙 𝑚𝑎𝑠𝑠 𝑖𝑛 𝑤𝑜𝑟𝑘 − 𝑢𝑝 𝑠𝑡𝑒𝑝 𝑚𝑎𝑠𝑠 𝑜𝑓 𝑝𝑟𝑜𝑑𝑢𝑐𝑡
𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 − 𝑤𝑜𝑟𝑘 𝑢𝑝 (𝑀𝐼) =
39.9 + 22 + 20.34 + 2 0.41
𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 − 𝑤𝑜𝑟𝑘 𝑢𝑝 (𝑀𝐼) =
84.24 0.41
𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 − 𝑤𝑜𝑟𝑘 𝑢𝑝 (𝑀𝐼) = 205.5
𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 − 𝑤𝑜𝑟𝑘 𝑢𝑝 𝑎𝑠 𝑎 % 𝑜𝑓 𝑜𝑣𝑒𝑟𝑎𝑙𝑙 𝑀𝐼 =
205.5 × 100 = 94.7% 217
Data adapted from Org. Biomol. Chem., 2011, 9, 1320. (http://dx.doi.org/10.1039/C0OB01069C) Some adaptations have been made: volumes and masses for some work-up chemicals have been estimated to allow metrics calculations. This has been done using best approximations based on the scale of the reaction where data was not provided. This education and training material has been created with funding from the Innovative Medicines Initiative Joint Undertaking under grant agreement n°115360, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution The views expressed in regards to education and training materials represent the aspiration of the CHEM21 consortium, although may not always be the view of each individual organisation
1. Calculate the Atom Economy of the reaction 𝐴𝑡𝑜𝑚 𝐸𝑐𝑜𝑛𝑜𝑚𝑦 (𝐴𝐸 ) =
𝑀𝑊 𝑜𝑓 𝑝𝑟𝑜𝑑𝑢𝑐𝑡(𝑠) × 100% 𝑀𝑊 𝑜𝑓 𝑎𝑙𝑙 𝑟𝑒𝑎𝑐𝑡𝑎𝑛𝑡𝑠
𝐴𝑡𝑜𝑚 𝐸𝑐𝑜𝑛𝑜𝑚𝑦 (𝐴𝐸 ) =
225.29 × 100% 136.15 + 107.16
𝐴𝑡𝑜𝑚 𝐸𝑐𝑜𝑛𝑜𝑚𝑦 (𝐴𝐸 ) =
225.29 × 100% 243.31
𝐴𝑡𝑜𝑚 𝐸𝑐𝑜𝑛𝑜𝑚𝑦 (𝐴𝐸 ) = 92.6%
2. Calculate the Reaction Mass Efficiency (RME) of the reaction
𝑅𝑀𝐸 =
𝑚𝑎𝑠𝑠 𝑜𝑓 𝑖𝑠𝑜𝑙𝑎𝑡𝑒𝑑 𝑝𝑟𝑜𝑑𝑢𝑐𝑡 × 100% 𝑡𝑜𝑡𝑎𝑙 𝑚𝑎𝑠𝑠 𝑜𝑓 𝑟𝑒𝑎𝑐𝑡𝑎𝑛𝑡𝑠
𝑅𝑀𝐸 =
0.41 × 100% 0.27 + 0.21
𝑅𝑀𝐸 =
0.41 × 100% 0.48
𝑅𝑀𝐸 = 85.4%
3. Calculate the Mass Intensity (MI) of the reaction
𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 (𝑀𝐼) =
𝑡𝑜𝑡𝑎𝑙 𝑚𝑎𝑠𝑠 𝑖𝑛 𝑎 𝑝𝑟𝑜𝑐𝑒𝑠𝑠 𝑜𝑟 𝑝𝑟𝑜𝑐𝑒𝑠𝑠 𝑠𝑡𝑒𝑝 𝑚𝑎𝑠𝑠 𝑜𝑓 𝑝𝑟𝑜𝑑𝑢𝑐𝑡
𝑀𝑎𝑠𝑠 = 𝐷𝑒𝑛𝑠𝑖𝑡𝑦 × 𝑉𝑜𝑙𝑢𝑚𝑒 𝑀𝑎𝑠𝑠 (𝑀𝑒𝐶𝑁) = 0.786 × 4 = 3.14𝑔 𝑀𝑎𝑠𝑠 (𝐷𝐶𝑀) = 1.33 × 30 = 39.9𝑔 𝑀𝑎𝑠𝑠 (1𝑀 𝑁𝑎𝐻𝐶𝑂3) = 1.1 × 20 = 22𝑔 𝑀𝑎𝑠𝑠 (1𝑀 𝐻𝐶𝑙 ) = 1.017 × 20 = 20.34𝑔
𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 (𝑀𝐼) =
0.27 + 0.21 + 1.09 + 3.14 + 39.9 + 22 + 20.34 + 2 0.41
𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 (𝑀𝐼) =
88.95 0.41
𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 (𝑀𝐼) = 217
4. What conclusions can you draw about the efficiency of the reaction from these calculations? For example:
Atom Economy is high – almost all of the atoms of the reactants are incorporated into the product AE is approximately equal to RME, good efficiency, no excess of reactants used MI not as good and this is mainly due to the work-up procedure (although MI would have been a lot higher if for example chromatography had been used for purification)
NB These calculations do not show that 2 equiv of a reagent (the borate ester) are being used– swamped in MI calculation due to the work-up, not included in RME. Also these calculations do not tell us anything about other parameters – i.e. the ‘bigger picture’
5. What proportion of the Mass Intensity is attributable to the work-up procedure? 𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 𝑤𝑜𝑟𝑘 − 𝑢𝑝 (𝑀𝐼) =
𝑡𝑜𝑡𝑎𝑙 𝑚𝑎𝑠𝑠 𝑖𝑛 𝑤𝑜𝑟𝑘 − 𝑢𝑝 𝑠𝑡𝑒𝑝 𝑚𝑎𝑠𝑠 𝑜𝑓 𝑝𝑟𝑜𝑑𝑢𝑐𝑡
𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 − 𝑤𝑜𝑟𝑘 𝑢𝑝 (𝑀𝐼) =
39.9 + 22 + 20.34 + 2 0.41
𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 − 𝑤𝑜𝑟𝑘 𝑢𝑝 (𝑀𝐼) =
84.24 0.41
𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 − 𝑤𝑜𝑟𝑘 𝑢𝑝 (𝑀𝐼) = 205.5
𝑀𝑎𝑠𝑠 𝐼𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 − 𝑤𝑜𝑟𝑘 𝑢𝑝 𝑎𝑠 𝑎 % 𝑜𝑓 𝑜𝑣𝑒𝑟𝑎𝑙𝑙 𝑀𝐼 =
205.5 × 100 = 94.7% 217
Data adapted from Org. Biomol. Chem., 2011, 9, 1320. (http://dx.doi.org/10.1039/C0OB01069C) Some adaptations have been made: volumes and masses for some work-up chemicals have been estimated to allow metrics calculations. This has been done using best approximations based on the scale of the reaction where data was not provided. This education and training material has been created with funding from the Innovative Medicines Initiative Joint Undertaking under grant agreement n°115360, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution The views expressed in regards to education and training materials represent the aspiration of the CHEM21 consortium, although may not always be the view of each individual organisation
