Of all our senses smell is still the most enigmatic, and chemists' relationship with this sense usually begins quite early in their training, much before they learn to appreciate the wonderful complexities of odor. And complex it is; while the other senses succumbed much earlier, it took until 2004 for a Nobel Prize to be awarded for work that teased out the nature of smell and the remarkable combinatorial mechanism by which the human nose senses odor.
The main quality of a chemical compound that enables us to smell it is volatility; the molecule should have a relatively low boiling point (or technically, vapor pressure) that allows whiffs of it to escape from its container and interact with the biochemical machinery inside our body. A lot of organic compounds have this quality so most young chemists encounter some kind of smell during their freshman or sophomore chemistry lab.
Smell is a powerful sense for human beings and we have inherited it from ancient creatures for whom it was an even more important guide to the external world. For most of our evolutionary history, smell was paramount in detecting mates and predators and in avoiding and locating nutritious and poisonous food. Thus it's not surprising to find students instinctively smelling compounds during their first few days in the lab. Lab instructors have to constantly remind them to refrain from doing this since many organic compounds are toxic or at least irritating, and in due time this habit is hammered out of most future chemists by the time they enter graduate school. But the students are actually perpetuating a grand tradition of chemical research. During the early days of chemistry, when there were no techniques for determining the structure and identities of molecules, color and smell were the two main qualities on which chemists could rely on for identifying specific compounds.
This was more than just a tool for academic research; forensic investigators could often identify the presence of poisons by their smells. For instance arsenic has a garlic-like smell, and hydrogen cyanide smells mildly of bitter almonds. During the depression, New York City police recruited "Smell Kelly", the subway sniffer whose bloodhound-like nose could locate chemical and gas spills and dead rats. Bad smells could also help during wartime. During World War 1, the characteristic smells of poison gases alerted soldiers to the ominous events that were to follow. The horseradish-like smell of deadly mustard gas was often disguised by a compound named xylyl bromide which smelled, of all things, like lilac; as the historian Richard Rhodes puts it, "thus it came to pass in the wartime spring that men ran in terror from a breeze scented with blossoming lilac shrubs". Unfortunately not all poisons have a compelling odor. Carbon monoxide is a notorious example, and a lot of deaths from the gas occur because people cannot smell it while it's building up around them. Sarin gas is another example; if sarin smelled like mustard, attacks like the 1995 Tokyo subway incident would be much harder to carry out. Sometimes as in case of natural gas, a potentially dangerous odorless agent can be spiked with minute concentrations of a highly smelly additive to make it possible to detect leaks. In case of natural gas that additive is methane thiol.
Which brings us to thiols and bad smells. Write a few words in a post about bad smells and you will usually have chemists swarming the comments section offering suggestions for their own favorite bad smell. Smells can often be subjective (and culture-specific, as in case of cheese), but if you ask chemists to universally agree upon one element in the periodic table that has succeeded in snaring the title of king of bad smells, they would probably settle upon sulfur, especially in the form of thiols. Thiols - also called mercaptans - are compounds with a sulfur bonded to a hydrogen, an atomic combination denoted by SH. The notoriety of thiols in causing bad smells is somewhat unfair since they also contribute to the smell of grapefruit and coffee, but there's no doubt that thiols are part of some nasty denizens of the smell world, including skunk spray and flatulence. In addition as the natural gas example indicates, the human nose is extraordinarily sensitive to thiol concentrations as low as a few parts in a billion.
Almost everyone who has an advanced degree in chemistry has smelt a thiol. My own experience with thiols dates back to my undergraduate days spent in a woefully under-equipped and safety-flaunting lab that would make OSHA investigators quake in their sterilized boots. There was one fume hood in the entire lab, and this was for housing a quaint piece of apparatus called Kipp's apparatus that was used to generate the simplest thiol, hydrogen sulfide, denoted by H2S. H2S contributes to the classic smell of rotten eggs.
The apparatus contained a few filings of iron sulfide in hydrochloric acid. The reaction between the two chemicals generated the gas which we would bubble into test-tubes for various experiments. We never tired of chasing each other around the lab, trying to thrust the test-tubes with the repulsive odor under each other's noses. Not once did our instructor tell us that not only is hydrogen sulfide smelly but it's also quite poisonous. I had a similar experience in my own private "lab" which was set up in a spare bathroom with little ventilation when I was a teenager. I used to happily dissolve safety pins and paper clips in nitric acid and watch the brownish green nitrogen dioxide gas rise up the test-tube. Nitrogen dioxide too has a very unpleasant smell and the whole house used to sometimes smell of it. Later when I started graduate school, I was quite startled to find out that the gas can be a silent killer; causing pulmonary edema until it suddenly kills you.
But back to hydrogen sulfide and thiols which generally lend a bad reputation to sulfur. Consider this post which asks whether the smell of butyl thiol is much worse than the smell of a gigantic goat cheese fire. That's a bit like asking if death by drowning is worse or better than death by burning. The point is that whatever the other virtues or hazards of sulfur, sulfur-containing compounds which smell bad will definitely turn people into social pariahs. Here's what happened when workers at the Esso Research Station in England were trying to make thioacetone from trithioacetone. Even if you don't know anything about these chemicals, you should have probably seen the "thio" in their names and guessed that trouble was waiting around the corner. Or in this case, a quarter of a mile downwind:
"Recently we found ourselves with an odour problem beyond our worst expectations. During early experiments, a stopper jumped from a bottle of residues, and, although replaced at once, resulted in an immediate complaint of nausea and sickness from colleagues working in a building two hundred yards away. Two of our chemists who had done no more than investigate the cracking of minute amounts of trithioacetone found themselves the object of hostile stares in a restaurant and suffered the humiliation of having a waitress spray the area around them with a deodorant.
The odours defied the expected effects of dilution since workers in the laboratory did not find the odours intolerable ... and genuinely denied responsibility since they were working in closed systems. To convince them otherwise, they were dispersed with other observers around the laboratory, at distances up to a quarter of a mile, and one drop of either acetone gem-dithiol or the mother liquors from crude trithioacetone crystallisations were placed on a watch glass in a fume cupboard. The odour was detected downwind in seconds."
I have seen few better examples of how you can gain instant notoriety through the wonders of chemistry. But if you think that thiols are the worst of all, think again. I will leave you with a conversation between two great twentieth-century scientists that illustrates just how bad compounds purportedly similar to thiols can be. Sulfur is followed in the periodic table by selenium and tellurium. Hydrogen sulfide smells awful and we know that elements in the same column in the table behave similarly. How might hydrogen selenium and hydrogen telluride smell? Linus Pauling (LP), widely acknowledged as the greatest chemist of the century, offered some helpful perspective to Matt Meselson (MP), inventor of the most beautiful experiment in biology.
LP: Well, Matt, you know about tellurium, the group VI element below selenium in the periodic chart of the elements?
MM: Uh, yes. Sulfur, selenium, tellurium ...
LP: I know that you know how bad hydrogen sulfide smells. Have you ever smelled hydrogen selenide?
MM: No, I never have.
LP: Well, it smells much worse than hydrogen sulfide.
MM: I see.
LP: Now, Matt, Hydrogen telluride smells as much worse than hydrogen selenide as hydrogen selenide does compared to hydrogen sulfide.
MM: Ahh ...
LP: In fact, Matt, some chemists were not careful when working with tellurium compounds, and they acquired a condition known as "tellurium breath." As a result, they have become isolated from society. Some have even committed suicide.
LM: But Matt, I'm sure that you would be careful. Why don't you think it over and let me know if you would like to work on the structure of some tellurium compounds?
I suspect that most graduate students would not embark on this project, even if it meant they got to work for Linus Pauling.
Added: Carbon-based Curiosities holds forth on some other nose-pinching entities.