In
organic chemistry, quaternary ammonium cations, also known as quats, are positively-charged
polyatomic ions of the structure [NR4+, where R is an
alkyl group, an
aryl group[1] or
organyl group. Unlike the
ammonium ion (NH+4) and the primary, secondary, or tertiary ammonium
cations, the
quaternary ammonium cations are permanently charged, independent of the
pH of their solution. Quaternary ammonium salts or quaternary ammonium compounds (called quaternary amines in
oilfield parlance) are
salts of quaternary ammonium cations.
Polyquats are a variety of engineered
polymer forms which provide multiple quat molecules within a larger molecule.
Quaternary ammonium compounds are prepared by the
alkylation of
tertiary amine. Industrial production of commodity quat salts usually involves hydrogenation of
fatty nitriles, which can generate primary or secondary amines. These amines are then treated with
methyl chloride.[4]
The quaternization of alkyl amines by
alkyl halides is widely documented.[5] In older literature this is often called a
Menshutkin reaction, however modern chemists usually refer to it simply as quaternization.[6] The reaction can be used to produce a compound with unequal alkyl chain lengths; for example when making
cationic surfactants one of the alkyl groups on the amine is typically longer than the others.[7] A typical synthesis is for
benzalkonium chloride from a long-chain alkyldimethylamine and
benzyl chloride:
Because of their resilience, many unusual anions have been isolated as the quaternary ammonium salts. Examples include
tetramethylammonium pentafluoroxenate, containing the highly reactive pentafluoroxenate (XeF− 5) ion.
Permanganate can be solubilized in
organicsolvents, when deployed as its N
Bu+ 4 salt.[9][10]
Concerns have been raised about the level of understanding of safety profile of quat disinfectants on people. As of August 2020, half of disinfectants the
United States Environmental Protection Agency suggested as effective against
COVID-19 contained one of the quats, and often a quat as the sole ingredient.[15]Salmonella and
E. coli O157:H7 exposed to quats have developed cross resistance to antibiotics. A subject of concern is the potential effect of increased use of quats related to
COVID-19 pandemic on antibiotic resistance in a larger microbial community in nature and engineered environment.[16]
Quaternary ammonium compounds are lethal to a wide variety of organisms except
endospores and
non-enveloped viruses, both having no accessible membrane coat to attack. It is possible to solve the endospore problem by adding chemicals which force them to germinate.[23][24] They have reduced efficacy against
gram-negative bacteria,
mycobacteria, and bacteria in
biofilms due to them having additional layers that need to be penetrated or disrupted. Some bacteria such as MRSA have acquired resistance genes, qacA/B and qacC/D, that pump the cation out of the cell.[22]
Phase transfer catalysts
In organic chemistry, quaternary ammonium salts are employed as
phase transfer catalysts (PTCs). Such catalysts accelerate reactions between reagents dissolved in immiscible solvents. The highly reactive reagent
dichlorocarbene is generated via PTC by reaction of
chloroform and aqueous
sodium hydroxide.[citation needed]
Fabric softeners and hair conditioners
In the 1950s,
distearyldimethylammonium chloride (DHTDMAC), was introduced as a
fabric softener. This compound was discontinued because the cation biodegrades too slowly. Contemporary fabric softeners are based on salts of quaternary ammonium cations where the fatty acid is linked to the quaternary center via ester linkages; these are commonly referred to as
betaine-esters or ester-quats and are susceptible to degradation, e.g., by
hydrolysis.[26] Characteristically, the cations contain one or two long
alkyl chains derived from fatty acids linked to an
ethoxylated ammonium salt.[27] Other cationic compounds can be derived from
imidazolium,
guanidinium, substituted amine salts, or quaternary
alkoxy ammonium salts.[28]
Cycocel (chlormequat chloride) reduces plant height by inhibiting the production of
gibberellins, the primary plant hormones responsible for cell elongation. Therefore, their effects are primarily on stem, petiole, and flower stalk tissues. Lesser effects are seen in reductions of leaf expansion, resulting in thicker leaves with darker green color.[32]
Quaternary ammonium compounds can display a range of health effects, amongst which are mild skin and respiratory irritation [37] up to severe caustic burns on skin and the
gastrointestinal wall (depending on concentration), gastrointestinal symptoms (e.g., nausea and vomiting), coma, convulsions, hypotension and death.[38]
Possible reproductive effects in laboratory animals
Quaternary ammonium-based disinfectants (Virex and Quatricide) were tentatively identified as the most probable cause of jumps in birth defects and fertility problems in caged lab mice. The quat ingredients in the disinfectants include
alkyl dimethyl benzyl ammonium chloride (ADBAC) and
didecyl dimethyl ammonium chloride (DDAC).[41][42] A similar link was tentatively identified in nurses.[43] The studies contradict earlier toxicology data reviewed by the U.S. Environmental Protection Agency (U.S. EPA) and the EU Commission.[44]
Quantification
The
quantification of quaternary ammonium compounds can be challenging. Some methods include precipitation of solid salts with
tetraphenylborate. Another method, an Epton titration, involves partitioning between water-
chloroform in the presence of an anionic dye. Individual cations are detectable by
ESI-MS and NMR spectroscopy.[4]
^
abKern A, Näther C, Studt F, Tuczek F (August 2004). "Application of a universal force field to mixed Fe/Mo-S/Se cubane and heterocubane clusters. 1. Substitution of sulfur by selenium in the series [Fe4X4(YCH3)4]2-; X = S/Se and Y = S/Se". Inorganic Chemistry. 43 (16): 5003–5010.
doi:
10.1021/ic030347d.
PMID15285677.
^Smith MB,
March J (2001). Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (5th ed.). New York, NY: Wiley-Interscience.
ISBN0-471-58589-0.
^Cocco AR, Rosa WL, Silva AF, Lund RG, Piva E (November 2015). "A systematic review about antibacterial monomers used in dental adhesive systems: Current status and further prospects". Dental Materials. 31 (11): 1345–1362.
doi:
10.1016/j.dental.2015.08.155.
PMID26345999.
^
abTischer, Maximilian; Pradel, Gabriele; Ohlsen, Knut; Holzgrabe, Ulrike (2 January 2012). "Quaternary Ammonium Salts and Their Antimicrobial Potential: Targets or Nonspecific Interactions?". ChemMedChem. 7 (1): 22–31.
doi:
10.1002/cmdc.201100404.
PMID22113995.
S2CID26326417.
^"Growth Retardants". Archived from
the original on September 25, 2011. Retrieved July 19, 2012. Wageningen Agricultural University, The Netherlands
^Anthoni, U.; Christophersen, C.; Hougaard, L.; Nielsen, P.H. (1991). "Quaternary ammonium compounds in the biosphere—An Example of a Versatile Adaptive Strategy". Comparative Biochemistry and Physiology Part B: Comparative Biochemistry. 99: 1–18.
doi:
10.1016/0305-0491(91)90002-U.
^Warshaw EM, Ahmed RL, Belsito DV, DeLeo VA, Fowler JF, Maibach HI, et al. (August 2007). "Contact dermatitis of the hands: cross-sectional analyses of North American Contact Dermatitis Group Data, 1994-2004". Journal of the American Academy of Dermatology. 57 (2): 301–314.
doi:
10.1016/j.jaad.2007.04.016.
PMID17553593.
^Office of Prevention, Pesticides and Toxic Substances, US EPA (August 2006). "Reregistration Eligibility Decision for Aliphatic Alkyl Quaternaries (DDAC)". Epa739-R-06-008.
Further reading
Zhang C, Cui F, Zeng GM, Jiang M, Yang ZZ, Yu ZG, et al. (June 2015). "Quaternary ammonium compounds (QACs): a review on occurrence, fate and toxicity in the environment". The Science of the Total Environment. 518–519: 352–362.
Bibcode:
2015ScTEn.518..352Z.
doi:
10.1016/j.scitotenv.2015.03.007.
PMID25770948.