This video continues a long-running project aimed at synthesizing large quantities of cubane. The focus is on two intermediate steps: the double debromination and double deprotection reactions, designated as Step 4 and 5 in the overall synthesis. The creator details the process, including refluxing material with sodium hydroxide and ethanol, and subsequent treatment with cold concentrated sulfuric acid. Challenges encountered include product impurities (resulting in unexpected orange/brown products), safety incidents involving bromine, and the inherent difficulties of scaling up chemical reactions, such as mechanical losses and managing large volumes. The video also discusses the purification process and the relatively good yields achieved despite the difficulties. A significant portion is dedicated to strategizing the next crucial step, photolysis (Step 6), weighing the pros and cons of scalable flow reactors versus simpler batch methods, and inviting community input. The overall goal remains to produce 100 grams of cubane, necessitating further production of earlier intermediates due to mass loss in the debromination step.
Synthesizing Cubane: Navigating Intermediate Steps and Scaling Challenges
0:00 Project Overview: The video details the ongoing effort to synthesize a significant quantity of cubane, focusing on Steps 4 (double debromination) and 5 (double deprotection), aiming to progress to the more challenging Step 6.
0:55 Step 4 (Double Debromination): This step involves refluxing tribromo ketow with sodium hydroxide in ethanol to remove bromine and was previously successful on a small scale. The goal is to scale up this process.
2:33 Reaction Setup: The creator sets up a reflux reaction using 100g of starting material and 1 liter of denatured ethanol, emphasizing the need for slow refluxing to prevent overheating.
4:42 Tribromo Ketow Yield & Safety: Initial yields of tribromo ketow (Step 3) were "okay" but improved to 66% after re-crystallization. A safety incident involving bromine penetrating cheap latex gloves and causing skin stains highlights the importance of proper PPE.
7:12 Product Appearance Issues (Attempt 1): After the initial reaction and workup, the product was an unexpected bright orange powder (should be off-white), suggesting an incomplete reaction or impurities. The creator decides to re-run the reaction with the same material for a longer duration.
11:46 Product Appearance Issues (Attempt 2): The second attempt yields a product that is still off-color (less orange, more brown/tar-like), but the creator proceeds, noting that the harshness of the next sulfuric acid step might tolerate some impurities.
13:58 Step 4 Yield: Weeks later, the dried product from Step 4 shows a 78% yield, which is considered good for a large-scale reaction despite impurities and mechanical losses.
15:08 Mass Loss and Production Needs: A significant challenge is the inherent mass loss (40%) in the debromination step, meaning much of the starting material's mass is discarded. More intermediate material is needed to reach the 100g cubane target.
16:13 Producing More Intermediates: The creator decides to produce more cyclopentanone, dioxane, and tribromo ketow off-camera, recalling a past flashboil incident during a Dean Stark setup as a cautionary tale.
20:15 Second Batch Yield: A subsequent, smaller-scale batch of tribromo ketow (from the re-run bromination) yields 54.4g, translating to a 28% overall yield from the ketow, still good enough to proceed.
21:37 Step 5 (Double Deprotection) Setup: Preparation for the sulfuric acid step involves dissolving the product in cold concentrated sulfuric acid, noting the large volumes and density involved. Safety measures, like ice baths, are crucial to control the exothermic reaction.
27:10 Reaction Process: The product is slowly added to the cold sulfuric acid, requiring careful monitoring and sustained cooling.
29:16 Post-Reaction Product: The deprotected product is obtained as a solid, varying in color from brownish-gray to brownish-orange across different batches, and still requires thorough drying.
30:17 Future Plans: Photolysis (Step 6): The creator discusses two methods for the final photolysis step: a scalable flow reactor (tubes around a UV lamp) with advantages in consistency but challenges in monitoring conversion, or a simpler batch ("jug") method that is less scalable but easier to observe. Audience input is solicited for this decision.
34:50 Overall Yield & Reflection: The video concludes with the overall series yield being around 66%. The creator acknowledges self-assessed slowness and messiness but remains focused on the ultimate goal of producing cubane.