Symmetry Plane and Molecular Chirality

 

 

The topic of asymmetry (chirality) in molecules , resulting in their optical activity (rotation of the plane of polarized light passing through them) , is discussed in this web page . Asymmetric (chiral) molecules have pairs of optical isomers , or enantiomers . Most biologically-derived molecules found in Nature are asymmetric , and are usually in the form of one specific enantiomer with a well-defined optical rotation . For example , common table sugar (sucrose , from sugar cane and sugar beets) has an optical rotation of aD20 = + 66.3– 66.8 (c = 26 , water) . In most chiral molecules the asymmetry is derived from one or more carbon atoms – “asymmetric centers” – having a tetrahedral sp3 coordination by four other different atoms or groups of atoms :

Certain types of molecules lacking any such tetrahedral asymmetric centers can also have non-superimposable mirror image pairs ; their pure enantiomers should similarly exhibit optical activity . The key concept demonstrated by such compounds is that their chirality is derived not from any particular asymmetric atoms in them , or even groups of atoms , but in the overall molecule itself . More specifically , a molecule will be asymmetric (chiral) if a symmetry plane fails to exactly bisect it , i.e. produce two mirror image “halves” on bisection ; conversely , if a molecule is bisected by a symmetry plane and two mirror image halves are produced , it will be symmetric (achiral) and won't have any optical isomers , nor will it demonstrate any optical activity . This is illustrated for the simple molecule above as follows :

The carbon atom in the center of the molecule is its asymmetric center and its “symmetry point” . This sort of chirality – based on a single asymmetric tetrahedral atom – is called “point chirality” . Asymmetric allenes are discussed in a section below ; they illustrate another type of chirality , “axial chirality” , which is based on a line of atoms in the molecule .

As can be seen in the above sketches , a molecule can be tested for chirality by employing either a mirror plane (external) or a symmetry plane (internal) . I consider the latter more fundamental in nature , because by comparing the two halves of the molecule bisected by the symmetry plane we can immediately see the “lop-sidedness” which is responsible for its asymmetry .

The electromagnetic fields in the photons of polarized light are all oriented in the same direction , so such photons are , in a sense , chiral . The photons of the polarized light diffract [bend] , with a rotation of their electromagnetic fields , as they pass through molecules . In asymmetric molecules they will diffract more in one half , as defined by the symmetry plane – not mirror plane – than in the other half , leading to a net diffraction , i.e. optical rotation . In symmetrical , achiral molecules the diffractions are identical in the two mirror image halves , but in opposite directions , leading to a net zero rotation of the polarized light beam and optical inactivity in the molecules :

Molecular chirality can be measured by the instrumental method of polarimetry [the references are presented at the end of the text , below] , whose principle is sketched above . A simple but illuminating classroom demonstration of polarimetry is provided in a YouTube video [FLV , 3:34 , 16,083 KB ; underlined blue hyperlinks can be clicked when online to download the referenced document , which will open in a new window] from the University of Nottingham , UK , in which small bottles of the l-(–)- and d-(+)-carvone enantiomers are placed between two squares of polarized plastic on a Viewgraph projector . The upper plastic square is slowly rotated to show the blocking of the diffracted photons exiting the carvone . A similar demonstration could likely be made using a small glass container of a concentrated solution of common sugar , whose molecules , as noted above , are chiral .

The topic of chirality in chemical compounds is discussed clearly in the Wikipedia web page , “Chirality (chemistry)”, and in another web page , “Fun with Chirality”, by Dr. Rod Beavon . These two sources are recommended as good overviews of chirality and optical activity in asymmetric molecules . In particular , the latter web page provides examples of various types of organic molecules that have no asymmetric tetrahedral carbon atoms , yet possess a global asymmetry and are chiral .

In this essay I'll discuss similar types of molecules whose chirality is derived from their overall asymmetry ; a bisecting symmetry plane fails to produce two mirror image halves in them . Such compounds will clearly demonstrate the important role of the symmetry plane with respect to optical activity in organic molecules . Their synthesis and study would make interesting research projects for inquisitive and energetic undergraduate organic chemistry students .

 

Diaryl Norbornene bis-Carboxylic Acids

 

In an undergraduate organic chemistry experiment I prepared 6,6-diphenylfulvene (first done by Thiele in 1900) from the condensation of cyclopentadiene with benzophenone , using sodium ethoxide as the strong base to form the cyclopentadienide anion . The fulvene was subsequently combined with maleic anhydride to synthesize a norbornene derivative (first done by Diels and Alder in 1928) :

In the above sketch , maleic acid , rather than the anhydride , is shown as the dienophile in the Diels-Alder reaction . The reason for this will be explained shortly .

If benzophenone is used as the diaryl ketone in the reaction sequence , the resulting norbornene will be optically inactive , despite having four asymmetric centers . A symmetry plane precisely bisecting the molecule will divide it into two identical halves . Molecules with one or more asymmetric carbon atoms yet having no optical isomers are called meso forms . Two examples of such compounds are meso-tartaric acid and meso-hydrobenzoin :

Thus , a norbornene derived from 6,6-diphenylfulvene and maleic acid will be meso , which can be visualized by examining the Norbornene-Fulvenes sketch above . However , a norbornene from an asymmetrical 6,6-diarylfulvene will be a racemate with 50% of each optical isomer , as shown in the sketch . A symmetry plane bisecting the molecule will produce two non-identical halves which will generate two corresponding enantiomers . It might be possible to separate those enantiomers using a suitable resolving agent .

A variety of unsymmetrical benzophenones can be prepared by the Friedel-Crafts acylation reaction (1877) , from the condensation of an aromatic compound with an aromatic acid chloride catalysed with a suitable Lewis acid , most commonly anhydrous AlCl3 . The following are two examples of Friedel-Crafts acylations for the preparation of unsymmetrical benzophenones :

The above images were scanned from the excellent collection of classic organic syntheses compiled by Shirley . My thanks to the copyright owner .

In another variation of the Friedel-Crafts acylation oxalyl chloride chlorocarbonylates an aromatic substrate in the presence of a catalytic quantity of anhydrous aluminum chloride . A second aromatic compound is added to the intermediate acid chloride/AlCl3 mixture in an inert solvent , such as methylene chloride , to form the unsymmetrical benzophenone . An undergraduate organic chemistry experiment from the University of Delaware (Professor D.F. Taber) illustrates this latter procedure :

Oxalyl chloride provides the ketone group linking the two dissimilar aryl groups . When combined with aluminum chloride in methylene chloride solvent at room temperature oxalyl chloride decomposes into phosgene , COCl2 , and carbon monoxide . It's thus a convenient (b.p. 63 C) source of the very unpleasant phosgene gas (b.p. 8 C ; phosgene was used as a chemical warfare agent in World War I) in Friedel-Crafts acylations . Oxalyl chloride , while being a convenient acylation reagent , is inefficient and uneconomical for this purpose , since three-quarters of the (COCl)2 molecule are wasted as the CO and HCl by-products .

As the first step in the suggested research project a stock of unsymmetrical benzophenones could be acquired , either by purchase of small sample quantities , or by their synthesis using one or other of the Friedel-Crafts acylation procedures . In the second phase of the project their corresponding unsymmetrical diarylfulvenes would be prepared . In the third part of the program the fulvenes would be combined with maleic acid in the Diels-Alder cyclizations , as sketched above . Finally , in the fourth stage the racemic norbornene derivatives would be resolved by the separation of their diasteroisomers , which would be prepared with a suitable resolving agent .

An optically active amine , such as d-(+)-dehydroabietylamine , would be the logical choice of resolving agent for the norbornene carboxylic acid products . To avoid possible complications , eg. amide formation , maleic acid , rather than its anhydride , was used in the Diels-Alder step :

Two other naturally-occurring amines , the alkaloids l-(–)-quinine and l-(–)-brucine , might also be examined as resolving agents to separate the norbornene racemates .

In one variation of this norbornene study , a series of unsymmetrical benzophenones could be designed and synthesized , and transformed into optically active diarylnorbornene bis-carboxylic acids . It would be interesting to see if there is a correlation between the degree of optical rotation and the degree of “lopsidedness” or size-imbalance of the molecule . Fluoro- , chloro- , bromo- , and iodobenzene could be acylated with benzoyl chloride (see the example of o-chlorobenzophenone above) . The 4-halo substituent is the symmetry-breaking component of the molecule . As this halogen atom's size increases , would its corresponding molecule rotate polarized light more and more ? [eg. draw a graph of the covalent radius of the halogen atom (x axis) versus the optical rotation of the halo compound (y axis) to see if there's any correlation] .

In a second series of unsymmetrical benzophenones various alkyl (and maybe even aryl) benzenes would similarly be acylated by benzoyl chloride . As the 4-alkyl group's size increases , what effect might be observed in the optical rotation of the corresponding norbornene bis-carboxylic acid ? In a third series of compounds , various groups with an increasing polarity would be installed on the benzophenones , while trying to keep their sizes roughly equal ; for example , when 4-R = –OCH3 (anisole) , –OH (phenol) , –NH2 (using acetanilide , then saponifying with base) , –NO2 (nitrobenzene) , –CN (benzonitrile) , –COOCH3 (methyl benzoate) , and so on . Note that the groups –OCH3 , –OH , and –NH2 are ring-activating and para-directors , while the groups –NO2 , –CN , and –COOCH3 are ring-deactivating and meta-directors .

In a fourth series of experiments , it would be interesting – and possibly somewhat challenging ! – to synthesize the individual diarylnorbornene bis-carboxylic acid optical isomers directly in the Diels-Alder step . Chiral catalysts have been studied and developed for Diels-Alder cyclizations . I've discussed this topic at some length in the Chemexplore menthol web page , to which the interested reader is referred . For example , the (AlCl3)3-S-(–)-phenylalanine catalyst suggested for the menthol synthesis , when applied to the norbornene preparation , might result in the production of the corresponding l-()-norbornene optical isomer . Or , using the corresponding (AlCl3)3-R-(+)-phenylalanine catalyst , the other d-(+)-norbornene enantiomer could be synthesized . If successful , this enantioselective Diels-Alder synthesis could save the researcher considerable time and effort (and expense) trying different techniques to separate the diasteroisomers of the diarylnorbornene bis-carboxylic acid and the resolving agent [such as d-(+)-dehydroabietylamine] .

The objective of all these experiments would be to determine to what extent the various substituents rotate the polarized light passing through them , and thereby gain some insight into how the light interacts with them . Is substituent size , polarity , or some other property the critical factor in the light diffraction ?

 

Optically Active Allene Compounds

 

Allenes (1,2-propadienes) have an “axial symmetry”, compared to the “point symmetry” of molecules with asymmetric tetrahedral carbon atoms . The central carbon (C2) has a linear sp hybridization , resulting in a 90 twist in the middle of the molecule . If there are two different substituents on each of C1 and C3 , two nonsuperimposable mirror images (optical isomers) will be produced :

If a symmetry plane bisects the molecule length-wise , we immediately see that its two halves are dissimilar :

This simple example nicely illustrates the general principle of chirality : in any sort of molecule with any sort of atoms , a symmetry plane is manoevered around in an attempt to exactly bisect it into two precisely identical mirror image halves. If the symmetry plane can't produce two identical halves , the molecule will be chiral and will have a pair of optical isomers . If the symmetry plane can produce two identical halves , the molecule will be achiral and will be optically inactive .

A variety of synthetic methods for allenes have been developed , some of them being rather complex and beyond the scope of this web page . The following is a suggested multi-stage synthesis of the chiral allene , 4-phenyl-2,3-butadienoic acid , which might be resolved into its separate enantiomers with a suitable resolving agent such as d-(+)-dehydroabietylamine :

Step 1 , the Claisen condensation (1881) of acetophenone and diethyl oxalate , is a well-known reaction . What I consider the “best” of several published procedures for the preparation of ethyl 2,4-dioxo-4-phenylbutyrate is illustrated in the above sketch . In step 2 , the two ketone groups are selectively reduced by sodium borohydride in 95% ethanol ; the ester group shouldn't be affected by borohydride , which is selective for the carbonyl group in aldehydes and ketones .

In step 3 , the diol is dehydrated to the allene (hopefully ; this may be a novel syntheis of allenes) . A non-volatile , strongly acidic catalyst , p-toluenesulfonic acid , would be present in the refluxing toluene (b.p. 111 C) . The water by-product could be conveniently distilled into a Dean-Stark tube :

This illustration was copied from the American Labware Inc. online catalogue . My thanks to the copyright owner . See also the Wikipedia web page , “Dean-Stark apparatus”.

This distillation apparatus provides two useful advantages . First , the progress of the reaction can be visually monitored by checking the volume of water azeotrope in the collection arm of the tube ; and second , the reaction can be driven to completion by removal of as much of the by-product water as possible (le Chatelier's Principle) . While benzene (b.p. 80 C) is commonly used as the solvent in such azeotropic distillations , toluene offers at least three advantages over it . First , dehydration reactions are faster in the higher boiling toluene (b.p. 111 C) . Second , the toluene azeotrope removes more water (79.8% with 20.2% water , b.p. 85 C) than a comparable volume of benzene (91.1% with 8.9% water , b.p. 69 C) . Third , toluene is probably less toxic and safer to use than the carcinogenic benzene . The somewhat oily meta-xylene (b.p. 139 C) is even more effective as an azeotropic distillation solvent (60% with 40% water , b.p. 95 C) , but is more difficult to remove from the product by rotary evaporation than toluene .

In the fourth step the allene ester is hydrolysed to the corresponding carboxylic acid . This might be accomplished by an alkaline saponification (aqueous NaOH) followed by acidification (aqueous HCl) and solvent extraction . The ester might also be directly hydrolysed to the acid in the suggested 5% aqueous oxalic acid solution . This is the strongly acidic medium (pH ~ 0.7) used by Royals and Horne in their synthesis of l-()-carvone from d-(+)-limonene . Their intermediate l-()-carvoxime was sensitive to mineral acids ; removal of its oxime group in HCl (aq) provided carvacrol rather than carvone . Use of 5% aqueous oxalic acid for removal of the oxime resulted in the formation of l-()-carvone in 7880% yield . Aqueous oxalic acid might be useful if the allene ester was as sensitive as carvone to mineral acids .

Finally , in the fifth and final step the racemic allene , 4-phenyl-2,3-butadienoic acid , would be resolved into its separate optical isomers via the formation of diasteromeric salts with an optically active amine such as d-(+)-dehydroabietylamine , or maybe with an alkaloid such as l-(–)-quinine or l-(–)-brucine . While dehydroabietylamine has been found to be quite effective as a resolving agent for carboxylic acids , this last step to obtain the separate enantiomers of 4-phenyl-2,3-butadienoic acid could require some experimentation to optimize the resolution .

As an alternate method to obtain the separate optical isomers of 4-phenyl-2,3-butadienoic acid directly , it might be possible to enantioselectively dehydrate the diol in step 3 using an optically active acid as the catalyst in place of p-toluenesulfonic acid . This dehydration might be accomplished with d-(+)-10-camphorsulfonic acid as the acid catalyst :

The diol could conceivably form a hydrogen-bonded intermediate complex with the camphorsulfonic acid , thereby “shaping” the newly-formed allene product , and imparting to it the specific stereochemistry of one or other of the optical isomers . Both d-(+)- and l-()-10-camphorsulfonic acid are commercially available , eg. from the Aldrich Chemical Company . Steps 3 and 4 might be combined by omitting the Dean-Stark tube and simply refluxing the diol , together with the camphorsulfonic acid catalyst , in the toluene solvent for several hours . The water azeotrope would then be distilled into the Dean-Stark tube , after which the toluene could be efficiently removed in a rotary evaporator .

A variety of ring-substituted acetophenones could be used to prepare a series of 4-phenyl-2,3-butadienoic acids for study . For example , Aldrich offers 4'-haloacetophenones at a moderate cost . They would be converted to 4-(4'-halophenyl)-2,3-butadienoic acids in the above reaction sequence . The 4'-halogen covalent radii and the optical rotations of the corresponding enantiomers would be examined for any correlation .

The Horner-Wadsworth-Emmons phosphonate modification (1961-63) of the Wittig reaction is now commonly used for the synthesis of allenes . The phosphine or phosphonate ylid will condense with a ketene to provide a respectable yield of an allene , as illustrated in the sketch below of such a reaction carried out by Fu and Ma in 2005 :

Our target molecules are the series of ethyl allene carboxylate esters , R1R2C=C=CHCOOEt , where R1 and R2 are various alkyl and aryl groups . Ethyl chloroacetate (ClCH2COOEt , b.p. 143 C) would provide the CHCOOEt part of the molecules . Triethyl phosphonoacetate can be formed in an essentially quantitative yield by heating ethyl chloroacetate with an equimolar quantity of triethyl phosphite , (EtO)3P , b.p. 156 C :

(EtO)3P + ClCH2COOEt ------ (heat , reflux) -----> (EtO)2(P=O)CH2COOEt + EtCl (g) .

Strongly basic tertiary amines such as triethylamine can also deprotonate triethyl phosphonoacetate . Rathke and Nowak simplified the Horner-Wadsworth-Emmons phosphonate reaction by using triethylamine as the deprotonating base with triethyl phosphonoacetate :

The two strongly basic tertiary amines DABCO ™ [1,4-diazabicyclo(2.2.2)octane , triethylenediamine] and DMAP (4-dimethylaminopyridine) , which are readily available at a moderate cost , are more nucleophilic at their nitrogen atoms than triethylamine ; their nucleophilic nitrogen lone pairs are more exposed and reactive than is the nitrogen lone pair in triethylamine :

Use of DABCO or DMAP as the deprotonating base with triethyl phosphonoacetate might accelerate the formation of its intermediate anionic state , the production of the intermediate ketene from the acid chloride , and the overall combination of the ketene with the anionic phosphonate . These two nucleophilic amines could provide a useful improvement to the phosphonate allene synthesis .

A convenient preparation of the acid chloride intermediates must next be devised . Many aliphatic carboxylic acids with at least one a-hydrogen atom (required for ketene formation) are commercially available at a modest cost , and can readily be converted to their corresponding acid chlorides by treatment with (for example) thionyl chloride . Aliphatic carboxylic acids can also be prepared by the familiar malonate synthesis :

(1) CH2(COOEt)2 + Na+ OEt --------> Na+ CH(COOEt)2 + EtOH

--------- (RBr) --------> RCH(COOEt)2 + NaBr (c) ;

(2) -------- (H3O+, heat) ---------> [RCH(COOH)2 ] ---------> RCH2COOH + CO2 (g) ;

(3) -------- (SOCl2) ---------> RCH2COCl + SO2 (g) + HCl (g) ;

(4) -------- (Et3N) ---------> RCH=C=O + Et3NH+ Cl .

Generally the carbonhalogen bonds in aromatic halides , eg. chlorobenzene , are too strong and inert to permit their use in the malonate synthesis . However , the carbonhalogen bonds in aromatic halides having electron-withdrawing groups ortho or para to them are more labile . Such is the case in o- and p-chloronitrobenzene ; the chlorine atom in these compounds can be displaced by strong nucleophiles . These aryl halides with labile carbonhalogen bonds might successfully be used in the malonate synthesis to provide substituted phenylacetic acids .

Chlorocarbonylation of hydrocarbons by phosgene or (more conveniently) oxalyl chloride , under light illumination or using a free radical initiator , would be a simpler and more direct method of synthesizing acid chlorides (discussed below in oxalyl chloride chlorocarbonylates ) . Peroxides such as benzoyl peroxide are well-known free radical catalysts in organic syntheses . Aromatic molecules with benzylic carbons can be selectively halogenated on those particular carbon atoms , rather than on the aromatic ring , in a free radical reaction catalysed by benzoyl peroxide . When heated to ~ 80 C , this peroxide decomposes into phenyl free radicals and carbon dioxide :

Ph(C=O)OO(O=C)Ph -------- (heat , ~ 80 C) -------> 2 Ph . + 2 CO2 (g) .

The phenyl radicals then catalyse the reaction of the reagent (halogenating agent) with the substrate (benzylic carbon atom) . N-Bromosuccinimide can brominate benzylic carbons with the participation of benzoyl peroxide as a free radical initiator :

The above is another image scanned from the organic syntheses compilation by Shirley . My thanks again to the copyright owner .

Suppose a similar reaction was carried out , but substituting oxalyl chloride for the N-bromosuccinimide . Would the benzylic carbon atom be chlorocarbonylated ?

R1CHR2 + ClCOCOCl -------- [benzoyl peroxide (cat.) / CCl4 , reflux , FUME HOOD !] -------> R1CH(COCl)R2 + CO (g) + HCl (g) ; R1 and R2 are aryl groups .

If successful , this would be a convenient method for preparing a series of diarylacetyl chlorides for use in the subsequent phosphonate allene synthesis with triethyl phosphonoacetate .

In another Chemexplore web page the stable radical cation salt “tris”, a type of Wurster Blue , was proposed for use as a catalyst in the addition of a variety of reagents to alkenes :

Tris is a mild one-electron oxidizer and is able to extract an electron from the p bond of olefins . It might be able to initiate free radical reactions like benzoyl peroxide , but at room temperature . Tris would be an interesting potential catalyst for the chlorocarbonylation of hydrocarbons and especially the benzylic sites of alkylated aromatic compounds by phosgene and oxalyl chloride .

Going backward to the step previous to the acid chlorides , we arrive at the series of unsymmetrical diarylmethanes ; they could likely be synthesized by the Friedel-Crafts alkylation of benzene derivatives (for example) by benzyl chloride (for example) . In the following sketch the starting materials fluoro- , chloro- , bromo- , and iodobenzene are converted in four separate steps into a series of racemic 4,4-diaryl-2,3-butadienoic acids , which might be resolved into their pairs of optical isomers , using dehydroabietylamine , in the final step :

Another interesting series of asymmetric allene acids could be similarly prepared from the 2- , 3- , and 4-halotoluenes (halo = F , Cl , Br , and I) , which are all commercially available (Aldrich Chemical Co.) in high purities and at a moderate cost . Twelve optically active allene carboxylic acids could be synthesized from these starting materials , starting at the second step in the above reaction sequence . Their optical rotations would then be compared with the unsubstituted chiral analogues , d-(+)- and l-()-4-phenyl-2,3-butadienoic acid , prepared from phenylacetyl chloride (commercially available) .

Other toluene derivatives with various polar substituents could also be examined : the nitrotoluenes , the tolunitriles , the methyl toluates (called “methyl methyl benzoates” in the Aldrich catalogue) , the methylanisoles , and so on . Hopefully , all of these substituted toluenes could be successfully converted into their corresponding acid chlorides by chlorocarbonylation with oxalyl chloride or phosgene , using a peroxide or “tris” as a catalyst .

Chiral allene esters have been synthesized using the reagent (1R)-()-10-(phenylsulfonyl)isoborneol attached to the Wittig reagent as the alcohol part of the ester . Subsequent hydrolysis removed this camphor-derived group (presumably it's recovered for re-use) to provide the chiral allene acid in a fair yield . Chiral allenes might be prepared directly in the phosphonate allene synthesis with a chiral amine as the deprotonating base . Dehydroabietylamine immediately comes to mind for this application . However , its primary amine group would react with the acid chloride in the ketene-forming step , so it must first be protected by N,N-dimethylation .

Several methods could be used for this N,N-dimethylation reaction . In the first one , formaldehyde (for N,N-dimethylolation) and formic acid (for reduction of the methylol groups to methyls) are simultaneously reacted with the NH2 group :

dehydroabietylNH2 + 2 HCHO + 2 HCOOH ----------> dehydroabietylN(CH3)2 + 2 CO2 (g)

+ 2 H2O .

In the second method , the dehydroabietylamine is “cooked” with trimethyl phosphate (b.p. 197 C) :

dehydroabietylNH2 + (CH3O)3P=O --------- (1) heat , ~ 150 C ---------->

dehydroabietylN(CH3)2 /(CH3O)(OH)2P=O ------- (2) NaOH (aq) , extract ---------->

dehydroabietylN(CH3)2 .

This latter N,N-dimethylation procedure has been successfully employed with a series of substituted anilines and with napthylamines ; presumably it would also be applicable to a high-boiling aliphatic amine such as dehydroabietylamine .

Alkylation of dehydroabietylamine's NH2 group by methyl iodide or dimethyl sulfate might also be possible , but would be less convenient than the suggested formaldehyde–formic acid and trimethyl phosphate methods of N,N-dimethylation .

The chiral alkaloid l-(–)-brucine , available at a moderate cost (Aldrich) also has a tertiary amine function and might induce some chirality into the allene ester product . Note that l-(–)-quinine , another common alkaloid resolving agent , has a secondary alcohol group that might be reactive (with the acid chloride) in the allene synthesis and so couldn't be used in this application .

 

Optically Active Carbon bis(Sulfine) , CS2O2

 

Sulfines are the S-oxides of thioaldehydes and thioketones :

Although sulfines seem to be strange and obscure organic compounds , one of them at least is familiar to most people . I'm sure the reader has been exposed to the naturally-occurring sulfine propanethial-S-oxide at one time or other . This unusual molecule is the strongly lachrymatory [tear-inducing] chemical formed when an onion is chopped up or sliced :

Chiral sulfines have been reported in the chemical literature . However , the sulfine I've been interested in for quite some time , and that should be chiral , is a most unusual one . I wondered if it might be possible to synthesize carbon bis(sulfine) , CS2O2 , by the selective S-oxidation of carbon disulfide : S=C=S + 2 [O] ------> O=S=C=S=O . Of course , carbon disulfide is well known to organic chemists as a foul-smelling , toxic , very volatile (b.p. 46 C) , and highly flammable reagent and solvent . Carbon disulfide is an excellent solvent for many organic and inorganic materials , most notably for rubber and sulfur . Similarly , dimethyl sulfoxide (DMSO , b.p. 189 C) is well known as a powerful polar organic solvent . I wondered if a compound such as CS2O2 might combine the solvent properties of both CS2 and DMSO : a super-solvent !

When I made a model of carbon bis(sulfine) I noticed that its molecular structure was similar to that of allene , and that it was chiral and so should have a pair of optical isomers :

To the best of my knowledge , carbon bis(sulfine) would be the simplest chiral molecule ever devised or discovered ; it has only five atoms , three of which are of different elements . The compound CHFClBr also has five atoms , but all five are different . As with the optically active allenes , CS2O2 has an axial chirality ; if a symmetry plane is placed along its S=C=S axis , the resulting left and right halves are dissimilar :

How might such a peculiar compound be prepared ? Several synthesis methods for sulfines have been developed over the past half century :

The second method , that of S-oxidation to form a sulfoxide analogue , seems most suitable for carbon disulfide . The “combo reagent” H2O2 + CH3ReO3 (cat.) provided excellent (> 90%) yields of sulfines from the corresponding substituted thiobenzophenones . The methyl rhenium(VII) trioxide was doing the actual S-oxidation via the CH3ReO2(O–O) intermediate , which was continuously regenerated by its H2O2 co-reagent . The selective S-oxidation of CS2 to CS2O2 using H2O2 + CH3ReO3 might thus be worthwhile investigating .

Another interesting possibility is suggested by an efficient industrial process for converting dimethyl sulfide (recovered in substantial volumes in the Kraft pulp and paper process) into dimethyl sulfoxide . U.S. patent 3,045,051 describes the remarkably selective S-oxidation of (CH3)2S to DMSO by oxygen in the presence of a catalytic quantity of nitrogen dioxide . As with CH3ReO3 , it's the NO2 that's actually doing the S-oxidation , with the oxygen continuously regenerating it from the nitric oxide effluent . This reaction is remarkably selective for sulfoxides ; apparently none of the corresponding sulfones were detected in the products (the O2 + NO2 oxidation can be successfully carried out with a variety of alkyl sulfides) :

Like carbon disulfide , dimethyl sulfide is foul-smelling , toxic , very volatile (b.p. 38 C) , and highly flammable . The analogous S-oxidation of CS2 by O2 + NO2 (cat.) seems reasonable . However , the Merck Index (8th edition , 1968) has this warning about CS2 : acute fire and explosion hazard , can be ignited by hot steam pipes (p. 208) ; flash point , 30 C ; explosive range , 1-50% (v/v) in air . I personally had a flash fire with CS2 one time ; fortunately , it was contained in our laboratory fume hood , and was messy to clean up but not serious . So the prospect of mixing carbon disulfide with oxygen and NO2 gives one pause for concern : certainly not an experiment for the timid or faint of heart ! [interesting YouTube video of the combustion of CS2 and nitrous oxide , N2O : FLV , 1:57 , 8261 KB] .

In a variation of this method , the oxygen reagent could be omitted and pure NO2 could be tried as the oxidizer , possibly in the presence of a catalyst such as Pt or Pd/carbon (palladized charcoal) :

CS2 + NO2 (g) ------- (catalyst , inert solvent , eg. CH2Cl2) --------> CS2O2 + N2 (g) ,

or possibly , CS2 + 2 NO2 (g) ------- (catalyst , etc.) --------> CS2O2 + 2 NO (g) .

While probably not as hazardous as the proposed reaction with oxygen , this latter experiment could also pose a significant explosion risk to the researcher , and so would require the observance of strict safety precautions should it ever be attempted .

Racemic carbon bis(sulfine) might be resolved into its separate optical isomers by an enantioselective chromatography method . Assuming that CS2O2 can actually be prepared , is reasonably stable , and isn't too reactive , it would be dissolved in a suitable inert solvent and passed through a column containing a solid chiral absorbent . Cellulose is a polymer comprised of chiral glucose units ; it , or a suitable derivative such as cellulose acetate or methylcellulose might be satisfactory as the chiral chromatography support .

 

References and Notes

 

polarimetry : J. Sodja-Bozic and T. Ogrin , “Polarimetry” [PDF , 91 KB] ; “Polarimetry” [web page , University of Adelaide , Australia] ; “Polarimeter” [web page , UCLA] ; an old-style polarimeter : Bellingham & Stanley technical bulletin P001 [PDF , 218 KB] ; a modern electronic polarimeter from Vernier Software & Technology : web page .

organic chemistry experiment : E.C. Wagner and W.C. Hunt , “Experiments with Cyclopentadiene”, J. Chem. Educ. 28 (6) , pp. 309-311(1951) ; fulvene and norbornene synthesis : J. Baldwin , Experimental Organic Chemistry , 2nd edition , McGraw-Hill , New York , 1970 ; 6,6-diphenylfulvene , pp. 56-57 ; norbornene compound , pp. 72-74 .

See also : J.H. Day , “The Fulvenes”, Chem. Rev. 53 (2) , pp. 167-189 (1953) ; E.D. Bergmann , “Fulvenes and Substituted Fulvenes”, Chem. Rev. 68 (1) , pp. 41-84 (1968) ; D.B. Knight et al. , “Synthesis of New Fulvene Derivatives”, J. Chem. Eng. Data 25 (2) , pp. 184-186 (1980) ; J.W. Hill , J.A. Jenson , and J.G. Yaritz, “Synthesis of Fulvenes Using Phase-Transfer Catalysis”, J. Chem. Educ. 63 (10) , p. 916 (1986) ; M.G. Thorn et al. , “Synthesis of 6-Aryl-6-Alkyl Fulvenes, 6-Aryl-6-Alkenyl Fulvenes , and Related Compounds”, U.S. Patent 7,420,097 B2 , to Chevron Phillips Chemical Co. , Sept. 2 , 2008 [PDF , 130 KB . Note : this file can be opened only with Adobe Acrobat Reader v. 6 or later . If desired , this application can be downloaded for free from Oldversion.com] ; Diels-Alder reaction of cyclopentadiene and maleic anhydride , experiment for organic chemistry students [PDF , 133 KB] ; K.J. Stone and R.D. Little , “An Exceptionally Simple and Efficient Method for the Preparation of a Wide Variety of Fulvenes”, J. Org Chem. 49 (11) , pp. 1849-1853 (1984) . These researchers condensed cyclopentadiene with a variety of aldehydes and ketones , using pyrrolidine as the base (to form the transient cyclopentadienide anion) ; they found that methanol was the best solvent for the reaction . “Acceptable to excellent yields” of fulvenes were claimed .

An organic salt (such as the acetate or propionate) of pyrrolidine has been used as the catalyst for the condensation of compounds having relatively acidic hydrogens a to a carbonyl group , with aldehyde and ketone carbonyls (the Knoevenagel-Doebner reaction , 1898-1900) . Ammonia and other amines such as pyridine and piperidine are also effective catalysts . For example , formaldehyde has been condensed with aldehydes to form a-substituted acroleins in good yields , using pyrrolidine propionate as the basic catalyst :

Ph–CH2–CH2–CHO + HCHO (37% aq)-------- (pyrrolidine propionate / isopropanol , 1 hr) ---------> Ph–CH2–(C=CH2)–CHO + H2O (99% yield) ; A. Erkkil and P.M. Pihko , J. Org Chem. 71(6) , pp. 2538-2541 (2006) .

The same sort of conditions could be examined in the reaction of cyclopentadiene with the various benzophenones . It would be interesting to try as a catalyst the strongly basic amine DABCO , with and without the organic acid (acetic or propionic) . To help drive the reaction to completion the water by-product could be removed azeotropically . Isopropanol (b.p. 82 C) forms an azeotrope with water (b.p. 80 C , 87.8% isopropanol , 12.2% water) ; additionally , some of the cyclopentadiene (b.p. 42 C) would undoubtedly carry over with the distilling azeotrope . As water and isopropanol are infinitely miscible , no separation of the water component would occur . A Soxhlet extraction apparatus could be used to remove the water from the azeotrope by continuously circulating it over 3A molecular sieves contained in its thimble :

This sketch – a cute animated GIF – of a Soxhlet extraction apparatus was copied from the Wikipedia web page , “Soxhlet extractor”. I thank the author of this sketch , and Wikipedia , for implied permission to reproduce it on this web page .

The above picture of 3A molecular sieves (bead form) is from the web page “Molecular Sieve 3A EDG (Ethanol Grade)”. My thanks to the copyright holder .

The 3A type of synthetic zeolite (with 3 pores) is specific for water molecules (2.8 diameter) . The water content of the azeotrope would be selectively absorbed by the sieves ; the larger diameter isopropanol and cyclopentadiene molecules would be excluded from them . Continuous recycling of the volatile components over the 3A molecular sieves would remove the by-product water and force the reaction to completion , leaving the non-volatile fulvene in solution in the reaction flask .

Shirley : D.A. Shirley , Preparation of Organic Intermediates , John Wiley , New York , 1951 . Phenyl-p-tolyl ketone was from pp. 260-261 ; o-chlorobenzophenone was from p. 73 ; 1-bromo-2-bromomethylnaphthalene was from p. 42 . If your Science Library doesn't have this book , you might be able to buy a second-hand copy from ABE , the Advanced Book Exchange .

oxalyl chloride chlorocarbonylates : Oxalyl chloride can acylate various substrates in several different ways . It can acylate aromatic rings in a Friedel-Crafts reaction to form an aroyl chloride . The reactive intermediate could be an acylium cation , [ClC=O]+ [AlCl4 ] :

ArH + ClCOCOCl ---- [AlCl3 / CS2] -----> ArCOCl + CO (g) + HCl (g) .

For example : M.E. Neubert and D.L. Fishel , “Preparation of 4-Alkyl-and 4-Halobenzoyl Chlorides : 4-Pentylbenzoyl Chloride”, Org. Syn. Coll. Vol. 7 , pp. 420-424 (1990) [PDF , 153 KB] ; P.E. Sokol , “Mesitoic Acid”, Org. Syn. Coll. Vol. 5 , pp. 706-708 (1973) [PDF , 147 KB] .

Sometimes the oxalyl nucleus remains intact , without any loss of carbon monoxide :

2 ArH + ClCOCOCl ---- [AlCl3 / CS2] -----> ArCOCOAr + 2 HCl (g) .

For example : C. Tzn , M. Ogliaruso , and E.I. Becker , “4,4'-Bis(dimethylamino)benzil”, Org. Syn. Coll. Vol. 5 , pp. 111-114 (1973) [PDF , 148 KB] .

Oxalyl chloride can also chlorocarbonylate alkanes under free radical catalysis . The acyl free radicals are usually generated by light (UV , visible) illumination and by decomposing organic peroxides , most often benzoyl peroxide . As mentioned in the text above , the stable free radical aminium compound “tris” might also be an effective catalyst in this application .

The yield of alkyl–CO–Cl product critically depends on the alkane substrate structure and conditions used . Unfortunately , to date only very low yields of benzylic–CO–Cl products have been obtained with oxalyl chloride ; apparently the intermediate benzylic free radicals are quite stable and are relatively unreactive , causing the chain of free radical reactions either to terminate or be diverted into the formation of alternate products . The following are several useful references from this area of research :

M.S. Kharasch and H.C. Brown , “The Photochemical Reactions of Oxalyl Chloride and Phosgene with Cyclohexane”, J. Amer. Chem. Soc. 62 (2) , p. 454 (1940) [DOI ; a JPEG image of the entire article is contained in this online abstract] ; idem. , “Carboxylation. I. The Photochemical and Peroxide-catalyzed Reactions of Oxalyl Chloride with Paraffin Hydrocarbons”, J. Amer. Chem. Soc. 64 (2) , pp. 329-333 (1942) ; M.S. Kharasch , S.S. Kane , and H.C. Brown , “Carboxylation. III. The Peroxide-catalyzed Reaction of Oxalyl Chloride with the Side-chains of Aralkyl Hydrocarbons . A Preliminary Study of the Relative Reactivity of Free Radicals”, J. Amer. Chem. Soc. 64 (7) , pp. 1621-1624 (1942) ; E. Hedaya and L.M. Kyle , “Bridge Chemistry of Paracyclophanes . The Mono- and Dichloroformylation of [2.2]Paracyclophane (Di-p-xylylene) with Oxalyl Chloride”, J. Org Chem. 32 (1) , pp. 197-199 (1967) :

I. Tabushi , J. Hamuro , and R. Oda , “Chlorocarbonylation of Adamantane”, J. Org Chem. 33 (5) , pp. 2108-2109 (1968) :

The chlorocarbonylation of cubane derivatives is described in a review by A. Bashir-Hashimi and G. Doyle , “Oxalyl Chloride in Photochemical Chlorocarbonylation of Cage Compounds”, Aldrichimica Acta 29 (2) , pp. 43-49 (1996) [PDF , 4357 KB ; the entire issue 2 must be downloaded to obtain the article] .

The chlorocarbonylation of hydrocarbons with oxalyl chloride creates a new carbon–carbon bond with the addition of another carbon atom to the substrate , and the acid chloride group is a very reactive , synthetically versatile “handle” on the molecule . Chlorocarbonylation should be a valuable synthetic method , but it still hasn't been optimized as such . I hope that some day the careful , systematic study of the chlorocarbonylation of hydrocarbons can be resumed , this time with the objective of optimizing the procedure into a well defined , trusted , standard synthesis method .

It would be especially desireable , in connection with a general synthesis of allenes , to develop a high yield chlorocarbonylation of benzylic compounds , which so far has remained elusive . The use of phosgene instead of oxalyl chloride as a chlorocarbonylating agent would also be desirable . As pointed out above , oxalyl chloride is an inefficient reagent for this purpose ; three-quarters of it is wasted as carbon monoxide and hydrogen chloride by-products . Phosgene , despite its unpleasant nature , is a cheap industrial chemical , and is more “atom-efficient” and “atom-economical” than oxalyl chloride . The pioneering research in chlorocarbonylation by Kharasch and Brown in the early 1940s showed that phosgene underwent the same sort of free radical reactions as oxalyl chloride , and was equally effective (or ineffective , as the case may be) as it .

unsymmetrical benzophenone : D.F. Taber and M.R. Sethuraman , “Unsymmetrical Diaryl Ketones from Arenes”, J. Org. Chem. 65 (1) , pp. 254-255 (2000) .

decomposes into phosgene : see the Neubert and Fishel , and Sokol Org. Syn. Coll. Vol. references immediately above .

dehydroabietylamine : W.J. Gottstein and L.C. Cheney , “Dehydroabietylamine . A New Resolving Agent”, J. Org Chem. 30 (6) , pp. 2072-2073 (1965) ; H. Komada , M. Okada , and H. Sumitomo , “Polymerization of Bicyclic Acetals . 6. Synthesis and Polymerization of (+)-(1R,5S)-6,8-Dioxabicyclo[3.2.1]octane”, Macromolecules 12 (1) , pp. 5-9 (1979) ; the purification of commercial dehydroabietylamine is described on p. 5 .

resolving agent : E. Nam , “Isolating the Enantiomers of 1-Phenylethylamine by Fractional Crystallization”, Vernier Polarimetry student experiment no. 4 , Microsoft Word document [DOC format , 191 KB] ; download from the Vernier polarimeter web page . The R-(+)- and S-(–)-1-phenylethylamine optical isomers are resolved using “natural” L-(+)-tartaric acid (see the next reference about a-methylbenzylamine ) .

brucine : B.S. Furniss et al. , “Resolution of () Octan-2-ol” [using brucine] , Vogel’s Textbook of Practical Organic Chemistry , 4th edition , Longman , London (UK) , 1978 ; pp. 578-580 . Two other resolutions of racemic compounds in this volume : a-methylbenzylamine by L-(+)-tartaric acid , pp. 577-578 , and DL-alanine in the selective enzymatic consumption of an enantiomer , pp. 580-581 . The technique of diastereomeric salt formation , such as with a carboxylic acid and an amine , is often referred to as the Pasteur method of resolution , named in honour of the great French organic chemist Louis Pasteur (1822-1895) , who was a pioneer investigator (1848) of chirality in organic molecules ; he resolved the optical isomers of tartaric acid by a manual separation of their different-shaped crystals , observed under a microscope .

synthetic methods for allenes : S. Ma , “Recent Advances in the Chemistry of Allenes”, Aldrichimica Acta 40 (4) , pp. 91-102 (2007) [PDF , 4050 KB ; the entire issue 4 must be downloaded to obtain the article] ; idem. , “Some Typical Advances in the Synthetic Applications of Allenes”, Chem. Rev. 105 (7) , pp. 2829-2872 (2005) . Earlier methods of preparing allenes are mentioned by R.B. Wagner and H.D. Zook , Synthetic Organic Chemistry , John Wiley , New York , 1953 ; pp. 40 , 56 , and 81 .

several published procedures : N.W. Fadnavis and K.R. Radhika , “Enantio- and Regiospecific Reduction of Ethyl 4-Phenyl-2,4-Dioxobutyrate with Baker's Yeast : Preparation of (R)-HPB Ester”, Tetrahedron : Asymmetry 15 (21) , pp. 3443-3447 (2004) [PDF , 286 KB] – see esp. p. 3445 ; X.P. Dai , X.Z. Li , Z.B. Zheng , and S. Li , “Synthesis and Biological Evaluation of Novel 1,5-Diarylpyrazole-3-Carboxamide Compounds as Inhibitors of ALK5” , Chinese Chem. Lett. , 17 (5) , pp. 609-612 (2006) [PDF , 151 KB] – see esp. p. 610 ; B.F. Abdel-Wahab , R.E. Khidre , and A.A. Farahat , “Pyrazole-3(4)-Carbaldehyde : Synthesis, Reactions and Biological Activity”, Arkivoc 2011 (i) , pp. 196-245 [PDF , 1149 KB] – see esp. pp. 205-206 ; C.E. Mounier et al. , “Pyruvate-extended Amino Acid Derivatives as Highly Potent Inhibitors of Carboxyl-Terminal Peptide Amidation”, J. Biol. Chem. 272 (8) , pp. 5016-5023 (1997) [PDF , 285 KB] – see esp. p. 5017 ; P. Herold et al. , “New Technical Synthesis of Ethyl (R)-2-Hydroxy-4-Phenylbutyrate of High Enantiomeric Purity”, Tetrahedron 56 (35) , pp. 6497-6499 (2000) .

The Claisen condensation of diethyl oxalate with methyl ethyl ketone and cyclohexanone is described in the following two Organic Syntheses procedures :

With methyl ethyl ketone : J.P. John , S. Swaminathan , and P.S. Venkataramani , “2-Methylcyclopentane-1,3-dione”, Org. Syn. Coll. Vol. 5 , pp. 747-750 (1973) [PDF , 157 KB] ; with cyclohexanone : H.R. Snyder , L.A. Brooks , and S.H. Shapiro , “Pimelic Acid”, Org. Syn. Coll. Vol. 2 , pp. 531-537 (1943) [PDF , 177 KB] .

sodium borohydride : L.F. Fieser and K.L. Williamson , Organic Experiments , 6th edition , D.C. Heath , Lexington (MA) , 1987 ; the sodium borohydride reduction of benzil to meso-hydrobenzoin is described on pp. 367-369 , and in earlier editions of Fieser's popular laboratory textbook .

Royals and Horne : E.E. Royals and S.E. Horne Jr. , “Conversion of d-Limonene to l-Carvone”, J. Amer. Chem. Soc. 73 (12) , pp. 5856-5857 (1951) .

carvacrol : R.A. Kjonaas and S.P. Mattingly , “Acid-Catalyzed Isomerization of Carvone to Carvacrol”, J. Chem. Educ. 82 (12) , pp. 1813-1814 (2005) .

Fu and Ma : C. Fu and S. Ma , “Efficient Preparation of 4-Iodofuran-2(5H)-ones by Iodolactonisation of 2,3-Allenoates with I2”, Eur. J. Org. Chem. 2005 (18) , pp. 3942-3945 .

Horner-Wadsworth-Emmons phosphonate modification : W.S. Wadsworth Jr. and W.D. Emmons , The Utility of Phosphonate Carbanions in Organic Synthesis, J. Amer. Chem. Soc. 83 (7) , pp. 1733-1738 (1961) ; web page . A facile synthesis of allenes from the combination of a phosphonate ylid with a ketene is experimentally described by : R.W. Lang and H.-J. Hansen , a-Allenic Esters from a-Phosphoranylidene Esters and Acid Chlorides : Ethyl 2,3-Pentadienoate”, Org. Synth. Coll. Vol. 7 , pp. 232-236 (1990) [PDF , 190 KB] .

Michaelis-Arbuzov reaction : A.K. Bhattacharya and G. Thyagarajan , “The Michaelis-Arbuzov Rearrangement”, Chem. Rev. 81 (4) , pp. 415-430 (1981) ; web page .

Rathke and Nowak : M.W. Rathke and M. Nowak , The Horner-Wadsworth-Emmons Modification of the Wittig Reaction Using Triethylamine and Lithium or Magnesium Salts, J. Org. Chem. 50 (15) , pp. 2624-2626 (1985) .

DABCO : B. Baghernejad , “1,4-Diazabicyclo[2.2.2]octane (DABCO) as a Useful Catalyst in Organic Synthesis”, Eur. J. Chem. 1 (1) , pp. 54-60 (2010) [PDF , 413 KB ; opens with Acrobat Reader v. 6 or later] ; web page . Note : “DABCO” is a registered trademark of Air Products & Chemicals Inc. .

DMAP : R. Murugan and E.F.V. Scriven , “Applications of Dialkylaminopyridine (DMAP) Catalysts in Organic Synthesis”, Aldrichimica Acta 36 (1) , pp. 21-27 (2003) [PDF , 9484 KB ; the entire issue 1 must be downloaded to obtain the article] ; D.J. Berry et al. , “Catalysis by 4-Dialkylaminopyridines ”, Arkivoc 2001 (i) , pp. 201-226 [PDF , 645 KB] ; Aldrich Chemical Co. Technical Bulletin AL-114 , “4-DMAP” [PDF , 239 KB] .

aromatic halides having electron-withdrawing groups : J.D. Roberts and M. Caserio , Basic Principles of Organic Chemistry , W.A. Benjamin , New York , 1965 , p. 844 ; J. March , Advanced Organic Chemistry , Reactions , Mechanisms , and Structure , 4th edition , John Wiley , New York , 1992 , pp. 649-651 .

Tris(4-bromophenyl)aminium : F.A. Bell , A. Ledwith , and D.C. Sherrington , “Cation-radicals : Tris-(p-bromophenyl)amminium Perchlorate and Hexachloroantimonate” , J. Chem. Soc. C 1969 (19) , pp. 2719-2720 ; G.W. Cowell , A. Ledwith , A.C. White , and H.J. Woods , “Electron-Transfer Oxidation of Organic Compounds with Hexachloroantimonate [SbCl2] Ion” , J. Chem. Soc. B 1970 (2) , pp. 227-231 .

extract an electron from the p bond : D.J. Bellville , D.D. Wirth , and N.L. Bauld , “The Cation-Radical Catalyzed Diels-Alder Reaction”, J. Amer. Chem. Soc. 103 (3) , pp. 718-720 (1981) ; D.J. Bellville and N.L. Bauld , “Selectivity Profile of the Cation Radical Diels-Alder Reaction”, J. Amer. Chem. Soc. 104 (9) , pp. 2665-2667 (1982) ; N. L. Bauld , J. T. Aplin , W. Yueh , and A. Loinaz , “A Non-Outer Sphere Mechanism for the Ionization of Aryl Vinyl Sulfides by Triarylaminium Salts”, J. Amer. Chem. Soc. 119 (47) , pp. 11381-11389 (1997) .

Chiral allene esters : T.M.V.D. Pinho e Melo et al. , “Novel Asymmetric Wittig Reaction : Synthesis of Chiral Allenic Esters”, Eur. J. Org. Chem. 2004 (23) , pp. 4830-4839 .

formaldehyde : R.N. Icke , B.B. Wisegarver , and G.A. Alles , b-Phenylethyldimethylamine”, Org. Syn. Coll. Vol. 3 , pp. 723-725 (1955) [PDF , 157 KB] .

trimethyl phosphate : W.A. Sheppard , “m-Trifluoromethyl-N,N-Dimethylaniline”, Org. Syn. Coll. Vol. 5 , pp. 1085-1087 (1973) [PDF , 167 KB] .

Sulfines : G. Opitz , “Sulfines and Sulfenes – the S-Oxides and S,S-Dioxides of Thioaldehydes and Thioketones”, Angew. Chem. Internat. Ed. Engl. 6 (2) , pp. 107-123 (1967) ; B. Zwanenburg , “The Chemistry of Sulfines”, Rec. Trav. Chim. Pays-Bas 101 (1) , pp. 1-27 (1982) ; W.A. Sheppard and J. Diekmann , “Sulfines”, J. Amer. Chem. Soc. 86 (9) , pp. 1891-1892 (1964) ; J. Strating , L. Thijs , and B. Zwanenburg , “A Thioaldehyde-S-Oxide”, Rec. Trav. Chim. Pays-Bas 83 (6) , pp. 631-636 (1964) ; B. Zwanenburg et al. , “Preparation of Sulfines by a Wittig Alkylidenation of Sulfur Dioxide”, Tet. Lett. 19 (9) , pp. 807-810 (1978) ; S. Krishnan , “Selected Reactions of Thiocarbonyl Compounds”, Caltech organic chemistry seminar , June 12th , 2006 [PDF , 2895 KB] ; PDF p. 8 .

propanethial-S-oxide : P.M. Burnham , “Propanethial-S-Oxide , The Lachrymatory Factor in Onions”, web page ; E. Block et al. , “Allium Chemistry : Microwave Spectroscopic Identification , Mechanism of Formation , Synthesis , and Reactions of (E,Z)-Propanethial S-Oxide , the Lachrymatory Factor of the Onion (Allium cepa)”, J. Amer. Chem. Soc. 118 (32) , pp. 7492-7501 (1996) .

Chiral sulfines : B. Zwanenburg , “Sulfine Chemistry”, Phosphorus, Sulfur, and Silicon and the Related Elements , 43 (1-2) , pp. 1-24 (1989) . Mention of chiral sulfines , and of their preparation by the condensation of carbanions with sulfur dioxide , is made in the online abstract of this review (I haven't been able to access the full text) .

thiobenzophenones : R. Huang and J.H. Espenson , “A Convenient Preparation of Sulfines (R2C=S=O) from Thioketones”, J. Org Chem. 64 (18) , pp. 6935-6936 (1999) .

U.S. patent 3,045,051 : J.G. Coma and V.G. Gerttula , “Production of Dialkyl Sulfoxides”, U.S. Patent 3,045,051 (to Crown Zellerbach Corp. , July 17th , 1962) [PDF , 221 KB . Note : this file can be opened only with Acrobat Reader v. 6 or later] .

enantioselective chromatography : G.B. Cox and N.M. Maier , “Fast Enantioselective Chromatography with 3-mm Particles” [PDF , 130 KB] ; “Chiral Columns”, web page .

 

 

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