The question is to propose a synthesis of indane from benzene. I started by the following. The black box is what I am not sure about. I know that the stable carbocation should be the middle one, this is why I am not sure. I need help here.
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3$\begingroup$ Better to do Friedel–Crafts acylation chemistry, then get rid of the carbonyl groups later, that avoids the problem which you pointed out $\endgroup$– orthocresolCommented Mar 2, 2018 at 10:05
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$\begingroup$ Related: Double alkylation of benzene to form tetralin $\endgroup$– orthocresolCommented Mar 2, 2018 at 10:07
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1$\begingroup$ If you treat your bromo alkyl compound with AIBN/tributyltinhydride it should cyclise to your product by a radical mechanism $\endgroup$– WaylanderCommented Mar 2, 2018 at 10:09
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$\begingroup$ @Waylander I'm not seeing it - that would give you a compound with two hydrogens too many, I think $\endgroup$– orthocresolCommented Mar 2, 2018 at 10:12
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$\begingroup$ @Waylander i.sstatic.net/r8xYd.jpg $\endgroup$– orthocresolCommented Mar 2, 2018 at 10:36
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3 Answers
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To prepare indane (6) from benzene, make the procedure as simple as possible and amenable to scale-up. Propiophenone (2) is readily available by Friedel-Crafts acylation of benzene with propionyl chloride (1). Removal of the carbonyl group of propiophenone and the creation of a carboxyl moiety can be achieved via the Willgerodt reaction to produce amide 3. Vigorous acid or base cleavage of the amide is possible but nitrous acid affords a mild route to carboxylic acid 4. One can use the AlCl3 F-C route again but hot polyphosphoric acid is a clean method for the intramolecular acylation without having to form the acid chloride. Finally, Clemmensen reduction of indanone (5) gives indane (6). Wolff-Kishner reduction is also a good option for the final step.
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$\begingroup$ Nice one, this Willgerodt reaction (unknown to me till now) was the missing link to the type of synthesis i was trying to get at as well! $\endgroup$ Commented Mar 5, 2018 at 12:41
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$\begingroup$ @AMM: I should add that the initially formed product in the formation of amide 3 is the thioamide, which undergoes hydrolysis under reaction conditions. $\endgroup$ Commented Mar 5, 2018 at 15:37
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Below is a suggested route for synthesizing indane starting from benzene and allyl bromide. I appreciate that this may not be a desirable answer for a school question but it is how one could perform the synthesis in real life and is based on high yield reactions that have been previously reported (see references, also note that this may not be the most efficient way):
References: 1) Synlett, 1999, No. 8, 1245. 2) J Org. Chem. Vol.78, No 19, 9772. 3) J Org. Chem. Vol.57, No 23, 1992. 4) Molecules 2014, Vol 19, No 5, 5599. 5) Catalysis letters 2011, Vol 141, No 4. 507.
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2$\begingroup$ Be quicker to do a Heck with your bromobenzene and acrylate. $\endgroup$ Commented Mar 3, 2018 at 23:10
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$\begingroup$ Yes, i was thinking of cross coupling approaches too and specifically converting the benzene to PhB(OH)2 and then suzuki coupling but didn't want to use transition metals or 'uncommon' ligands for this one and keep it more 'organic'. The Heck is a reasonable suggestion though. I assume you would follow with hydrogenation of the double bond and hydrolysis to get the acid afterwards ? $\endgroup$ Commented Mar 3, 2018 at 23:43
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$\begingroup$ Exactly so, then polyphosphoric acid for the cyclisation $\endgroup$ Commented Mar 4, 2018 at 0:00
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I think the effeicient and better way to synthesize the given compound with greater yield from Benzene may be this,
answered Mar 2, 2018 at 14:30
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1$\begingroup$ I dont think this is a good way since you will get a mixture of all possible Friedel Crafts products such as PhCH2CH2CH2Ph etc. $\endgroup$ Commented Mar 3, 2018 at 19:28
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$\begingroup$ Not if you add benzene into the mixture or use a lanthanide Lewis acid in a flow system with a dichloropropane and benzene feed in the appropriate ratio. $\endgroup$ Commented Mar 3, 2018 at 20:41
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$\begingroup$ @Beerhunter This doesn't sound very practical and i cant find it in the literature. It does sound very interesting though. Can you provide a reference please as it might be of use to me in general (it doesn't have to be exactly the same reaction)? Thank you. $\endgroup$ Commented Mar 4, 2018 at 13:35
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$\begingroup$ The concept will have been demonstrated, but not necessarily on exactly the same compounds. The literature is just what other people have done, which doesn't always make it the best way to do something. The methodology of using something like scandium triflate has been demonstrated. Using flow chemistry to control stoichiometry has been also. $\endgroup$ Commented Mar 4, 2018 at 13:37
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2$\begingroup$ This route is problematic: 1) alkylation of benzene via F-C gives products that are more reactive than benzene; 2) polymerization here is a problem IF the primary carbocation were the reacting species; 3) n-propyl chloride gives isopropylbenzene. Rearrangement of the primary to the the secondary carbocation occurs. Expect the same problem here. $\endgroup$ Commented Mar 5, 2018 at 15:51