A Real-life Real-time Problem

kilomentor | 17 June, 2007 12:23

A friend is having a problem. He can’t tell me much about it; so often the case. It is proprietary. It involves the reduction of a nitro group (presumably to an amine) with the reagent sodium sulfide. The problem is the yield. The question for you readers: How much help can one be when one doesn’t know the details of a particular situation?

Perhaps you can’t be much help at all; but the situation does provide the opportunity to be mindful of two rules of thumb, that, if they don’t work in this case, will upon repeated recollection be useful and solve problems. This reduction of a nitro functionality to an amine using sodium sulfide gives me the chance to commend both of them to you, again, at the same time.

Rule 1

More problems result from impure starting materials than from any other cause

Sodium sulfide is easy to get in an impure form. In Fieser and Fieser Vol. 1 (1967) pg. 1104 it is reported that the reagent sodium sulfide nonahydrate decomposes on contact with air; a freshly opened bottle should be used. In Organic Syntheses, Coll. Vol. IV (1963) pg.32 sodium sulfide nonahydrate is used also for the reduction of an aromatic nitro. Note 1 reads, “Merck’s reagent grade of sodium sulfide nonahydrate was used. Since sodium sulfide decomposes on contact with air, a freshly opened bottle should be employed. “Sodium sulfhydrate” (Hooker Electrochemical Company hydrated sodium hydrosulfide) is also satisfactory; the amount should be based upon the formula NaHS.2H2O and an equivalent amount of sodium hydroxide ……is require.” The same advice about instability but here an additional problem is noted. There are other reagent combinations which can be used to replace the reagent but the degree of hydration of these is sufficiently obscure that Organic Syntheses feels it needs to tell you what constitution to assume.

In Fieser & Fieser Vol. 3 (1972) pg. 269 under the heading, Sulfides, the authors list four types

(a) sodium sulfide nonahydrate crystalline, Na2S.9 H2O(

b) technical fused chip sodium sulfide, 60% Na2S (mol. wt. 78.06)

(c ) Sodium polysulfide. Sulfur (at. wt. 32.07) is dissolved by heating and stirring in aqueous or alcoholic sodium sulfide.

(d) Ammonium sulfide. aqueous or alcoholic ammonia is saturated with hydogen sulfide

My first questions are do we know exactly what we are using? Do we have a valid analysis and have we taken the required precautions to keep the reagent intact before it encounters the substrate in the reactor?

I can imagine that on a kilo-scale ,weighing out and storing the reagent in the absence of air could be a problem. I don’t know that it is a problem, but this reagent is not inert and given that problems with starting materials are frequent, it is a question worth asking.

Rule 2

Organic chemists have a bad habit of not writing balanced equations and in oxidation and reduction reactions this has an annoying habit of causing them to get the stoichiometry wrong. So do you have the stoichiometry correct?

R-NO2 + 3Na2S + 6NH4Cl gives R-NH2 + 3S +2H2O + 6NaCl + 6NH3

Note that all the sulfur from the sodium sulfide ends up as zero valent elemental sulfur which is a co-product. All the six equivalents of acid (here NH4Cl) are used to protonate the amine being generated (2 protons) and the two oxygens being converted into water (4 protons). The sulfide is just providing a supply of electrons.

What this equation may also be telling us is that if we get the amount of acid too low we may also stop the reaction. Six equivalents of acid are required to meet the stoichiometry.

The essential nature of these hydrogens are also suggested at by a paragraph in Fieser & Fieser Vol. 9 pg. 434 treating the reagent sodium sulfide-thiophenol:

‘Nitroalkenes substituted with at least one aryl group are reduced to alkenes rapidly at room temperature by reaction with sodium sulfide nonahydrate and thiophenol in DMF. Thiophenol is essential as a proton source for this reduction; it is converted into diphenyl disulfide during the reaction.” [my italics]

So again I repeat stoichiometry may well not be the problem in this particular real life case, but knowing nothing else except that it is a redox reaction- take heed check the stoichiometry. The error is so frequent it ought to be laughable but I can tell you from experience- it isn't.