ALDEHYDES AND KETONES
are organic compounds containing a fragment >C=O (carbon linked by a double bond to oxygen, it is called carbonyl).
In aldehydes, the carbonyl carbon is connected to the H atom and the organic group R (general formula RHC=O), and in ketones - to two organic groups (general formula R2C=O). Also on topic:
ORGANIC CHEMISTRY
Nomenclature of aldehydes and ketones. The –(H)C=O group is called aldehyde; it has only one free valence to bind with organic groups, this allows it to be located only at the end of the hydrocarbon chain (but not in the middle). When compiling the name of an aldehyde, the name of the corresponding hydrocarbon is indicated, to which the suffix “al” is added, for example, methanal H2C=O, ethanal H3CC(H)=O, propanal H3CH2C(H)=O. In more complex cases, the carbon chain of the R group is numbered, starting with the carbonyl carbon, then using numerical indices to indicate the position of the functional groups and various substituents.
Rice. 1. NOMENCLATURE OF ALDEHYDES
. Substituting and functional groups, as well as their corresponding digital indices, are highlighted in different colors.
For some aldehydes, trivial (simplified) names that have developed historically are often used, for example, formaldehyde H2C=O, acetaldehyde H3CC(H)=O, crotonaldehyde CH3CH=CHC(H)=O.
Unlike the aldehyde group, the ketone group >C=O can also be located in the middle of the hydrocarbon chain, therefore, in simple cases, indicate the names of organic groups (mentioning them in ascending order) and add the word “ketone”: dimethyl ketone CH3–CO–CH3, methyl ethyl ketone CH3CH2 –CO–CH3. In more complex cases, the position of the ketone group in the hydrocarbon chain is indicated by a digital index, adding the suffix “ on”
" The numbering of the hydrocarbon chain begins from the end that is closest to the ketone group (Fig. 2).
Rice. 2. NOMENCLATURE OF KETONES
. Substituting and functional groups and their corresponding digital indices are highlighted in different colors.
For the simplest ketone CH3–CO–CH3, the common name is acetone.
Chemical properties of aldehydes and ketones
are determined by the characteristics of the carbonyl group >C=O, which has polarity - the electron density between the C and O atoms is unevenly distributed, shifted to the more electronegative O atom. As a result, the carbonyl group acquires increased reactivity, which is manifested in various addition reactions at the double bond. In all cases, ketones are less reactive than aldehydes, in particular, due to the steric hindrance created by the two organic R groups, formaldehyde H2C=O most easily participates in reactions.
1. Addition via the double bond C=O.
When interacting with alcohols, aldehydes form hemiacetals - compounds containing both an alkoxy and a hydroxy group at one carbon atom: >C(OH)OR. Hemiacetals can further react with another alcohol molecule, forming full acetals - compounds where one carbon atom simultaneously contains two RO groups: >C(OR)2. The reaction is catalyzed by acids and bases (Figure 3A). In the case of ketones, the addition of alcohols to the double bond in C=O is difficult.
In a similar way, aldehydes and ketones react with hydrocyanic acid HCN, forming hydroxynitriles - compounds containing an OH and CN group at one carbon atom: >C(OH)CєN (Fig. 3B). The reaction is noteworthy in that it allows the carbon chain to increase (a new C-C bond appears).
In the same way (opening the C=O double bond), ammonia and amines react with aldehydes and ketones, the addition products are unstable and condense with the release of water and the formation of a C=N double bond. In the case of ammonia, imines are obtained (Fig. 3C), and from amines so-called Schiff bases are formed - compounds containing the fragment >C=NR (Fig. 3D). The product of the interaction of formaldehyde with ammonia is somewhat different - it is the result of the cyclization of three intermediate molecules, resulting in the framework compound hexamethylenetetramine, used in medicine as the drug urotropine (Fig. 3D).
2. Condensation reactions. For aldehydes and ketones, condensation is possible between two molecules of the same compound. With such condensation of aldehydes, the double bond of one of the molecules opens, forming a compound containing both an aldehyde and an OH group, called an aldol (aldehyde alcohol). The condensation that occurs is called aldol, and this reaction is catalyzed by bases (Fig. 4A). The resulting aldol can further condense to form a C=C double bond and release condensation water. The result is an unsaturated aldehyde (Fig. 4A, crotonaldehyde). This condensation is called crotonic condensation after the name of the first compound in the series of unsaturated aldehydes. Ketones are also capable of participating in aldol condensation (Fig. 4B), but the second stage, croton condensation, is difficult for them. Molecules of various aldehydes, as well as both an aldehyde and a ketone, can jointly participate in aldol condensation; in all cases, the carbon chain lengthens. The crotonaldehyde obtained at the last stage (Fig. 4A), possessing all the properties of aldehydes, can further participate in aldol and croton condensation when interacting with the next portion of acetaldehyde from which it was obtained (Fig. 4B). In this way, it is possible to lengthen the hydrocarbon chain, obtaining compounds in which single and double bonds alternate: –CH=CH–CH=CH–.
The condensation of aldehydes and ketones with phenols involves the removal of the carbonyl O atom (in the form of water), and the methylene group CH2 or a substituted methylene group (CHR or CR2) is inserted between two phenol molecules. This reaction is most widely used to produce phenol-formaldehyde resins (Fig. 5).
Rice. 5. CONDENSATION OF PHENOL WITH FORMALDEHYDE
3. Polymerization of carbonyl compounds occurs with the opening of the C=O double bond and is characteristic mainly of aldehydes. When aqueous solutions of formaldehyde are evaporated in vacuum, a mixture of cyclic compounds (mainly trioxymethylene) and linear products with a small chain length n = 8–12 (paraforms) is formed. By polymerizing the cyclic product, polyformaldehyde is obtained (Fig. 6), a polymer with high strength and good electrical insulating properties, used as a structural material in mechanical and instrument making.
Rice. 6. FORMALDEHYDE POLYMERIZATION PRODUCTS
4. Reduction and oxidation. Aldehydes and ketones are intermediate compounds between alcohols and carboxylic acids: reduction leads to alcohols, and oxidation leads to carboxylic acids. Under the action of H2 (in the presence of a Pt or Ni catalyst) or other reducing reagents, for example, LiAlH4, aldehydes are reduced, forming primary alcohols, and ketones - secondary alcohols (Fig. 7, schemes A and B).
The oxidation of aldehydes to carboxylic acids occurs quite easily in the presence of O2 or under the action of weak oxidizing agents, such as an ammonia solution of silver hydroxide (Fig. 7B). This spectacular reaction is accompanied by the formation of a silver mirror on the inner surface of the reaction device (usually an ordinary test tube); it is used for the qualitative detection of the aldehyde group. Unlike aldehydes, ketones are more resistant to oxidation; when heated in the presence of strong oxidizing agents, for example, KMnO4, mixtures of carboxylic acids are formed that have a shortened (compared to the original ketone) hydrocarbon chain.
Rice. 7. REDUCTION AND OXIDATION OF ALDEHYDES AND KETONES
Additional confirmation that aldehydes occupy an intermediate position between alcohols and acids is the reaction that results in an alcohol and a carboxylic acid from two aldehyde molecules (Fig. 8A), i.e. one aldehyde molecule is oxidized and the other is reduced. In some cases, the two resulting compounds—an alcohol and a carboxylic acid—further react with each other, forming an ester (Fig. 8B).
Rice. 8 .
SIMULTANEOUS OXIDATION AND REDUCTION OF ALDEHYDES
Ketanov 10 mg 100 pcs. film-coated tablets
pharmachologic effect
NSAID, derivative of pyrrolysine-carboxylic acid. It has a pronounced analgesic effect, and also has anti-inflammatory and moderate antipyretic effects. The mechanism of action is associated with inhibition of the activity of COX, the main enzyme in the metabolism of arachidonic acid, which is a precursor of prostaglandins, which play a major role in the pathogenesis of inflammation, pain and fever.
Composition and release form Ketanov 10 mg 100 pcs. film-coated tablets
Tablets - 1 tablet: ketorolac tromethamine 10 mg.
10 pieces. — contour cell packaging (10) — cardboard packs.
Description of the dosage form
Film-coated tablets.
Directions for use and doses
For adults, when taken orally - 10 mg every 4-6 hours, if necessary - 20 mg 3-4 times a day.
For intramuscular administration, a single dose is 10-30 mg, the interval between injections is 4-6 hours. The maximum duration of use is 2 days.
Maximum doses: when taken orally or intramuscularly - 90 mg/day; for patients weighing up to 50 kg, with impaired renal function, as well as for persons over 65 years of age - 60 mg/day.
Pharmacodynamics
The analgesic effect occurs after approximately 30 minutes, the maximum analgesic effect develops after 1-2 hours. The duration of the analgesic effect is 4-6 hours or more, depending on the dose. Does not have a sedative or anxiolytic effect, does not affect opioid receptors. It does not have a depressant effect on the respiratory center and does not enhance respiratory depression and sedation caused by opioid analgesics. Does not cause drug dependence. No withdrawal symptoms occur after abrupt cessation of use. Suppresses platelet aggregation and may cause prolongation of bleeding time. Restoration of platelet function occurs 24-48 hours after discontinuation of the drug.
Pharmacokinetics
When taken orally, it is absorbed from the gastrointestinal tract. Cmax in blood plasma is achieved 40-50 minutes after both oral and intramuscular administration. Eating does not affect absorption. Plasma protein binding is more than 99%.
T1/2 ;- 4-6 hours both after oral administration and after intramuscular administration.
More than 90% of the dose is excreted in the urine, unchanged - 60%; the remaining amount is through the intestines.
In patients with impaired renal function and the elderly, the elimination rate decreases, T1/2 increases.
Indications for use Ketanov 10 mg 100 pcs. film-coated tablets
For short-term relief of moderate and severe pain of various origins.
Contraindications
Erosive and ulcerative lesions of the gastrointestinal tract in the acute phase, the presence or suspicion of gastrointestinal bleeding and/or cerebral hemorrhage, a history of blood coagulation disorders, conditions with a high risk of bleeding or incomplete hemostasis, hemorrhagic diathesis, moderate and severe renal dysfunction ( serum creatinine content more than 50 mg/l), the risk of developing renal failure due to hypovolemia and dehydration; “aspirin triad”, bronchial asthma, nasal polyps, history of angioedema, preventive pain relief before and during surgery, childhood and adolescence up to 16 years of age, pregnancy, childbirth, lactation, hypersensitivity to ketorolac, acetylsalicylic acid and other NSAIDs .
Application of Ketanov 10 mg 100 pcs. film-coated tablets during pregnancy and breastfeeding
Contraindicated during pregnancy, during childbirth and during lactation (breastfeeding).
Ketorolac is contraindicated for use as a premedication, maintenance of anesthesia and for pain relief in obstetric practice, since its influence may increase the duration of the first stage of labor. In addition, ketorolac may inhibit uterine contractility and fetal circulation.
Use with caution in patients with impaired renal function.
Use in children
Contraindicated in children and adolescents under 16 years of age.
special instructions
Use with caution in patients with impaired liver and kidney function, chronic heart failure, arterial hypertension, in patients with erosive and ulcerative lesions of the gastrointestinal tract and a history of bleeding from the gastrointestinal tract.
Ketorolac should be used with caution in the postoperative period in cases where particularly careful hemostasis is required (including after resection of the prostate gland, tonsillectomy, in cosmetic surgery), as well as in elderly patients, because The half-life of ketorolac is prolonged and plasma clearance may be reduced. In this category of patients, it is recommended to use ketorolac in doses close to the lower limit of the therapeutic range. If symptoms of liver damage, skin rash, or eosinophilia appear, ketorolac should be discontinued. Ketorolac is not indicated for use in chronic pain syndrome.
Impact on the ability to drive vehicles and operate machinery
If drowsiness, dizziness, insomnia or depression appear during treatment with ketorolac, special care must be taken when engaging in potentially hazardous activities that require increased attention and speed of psychomotor reactions.
Overdose
Symptoms: (with a single dose) abdominal pain, nausea, vomiting, peptic ulcers, impaired renal function (these symptoms disappeared after discontinuation of the drug). Treatment: symptomatic therapy. Dialysis does not significantly remove ketorolac from the blood.
Side effects of Ketanov 10 mg 100 pcs. film-coated tablets
From the cardiovascular system: rarely - bradycardia, changes in blood pressure, palpitations, fainting.
From the digestive system: nausea, abdominal pain, diarrhea are possible; rarely - constipation, flatulence, feeling of gastrointestinal fullness, vomiting, dry mouth, thirst, stomatitis, gastritis, erosive and ulcerative lesions of the gastrointestinal tract, liver dysfunction.
From the central nervous system and peripheral nervous system: anxiety, headache, drowsiness are possible; rarely - paresthesia, depression, euphoria, sleep disturbances, dizziness, changes in taste, visual disturbances, motor disorders.
From the respiratory system: rarely - respiratory failure, attacks of suffocation.
From the urinary system: rarely - increased frequency of urination, oliguria, polyuria, proteinuria, hematuria, azotemia, acute renal failure.
From the blood coagulation system: rarely - nosebleeds, anemia, eosinophilia, thrombocytopenia, bleeding from postoperative wounds.
From the metabolic side: ;possible increased sweating, swelling; rarely - oliguria, increased levels of creatinine and/or urea in the blood plasma, hypokalemia, hyponatremia.
Allergic reactions: possible skin itching, hemorrhagic rash; in isolated cases - exfoliative dermatitis, urticaria, Lyell's syndrome, Stevens-Johnson syndrome, anaphylactic shock, bronchospasm, Quincke's edema, myalgia.
Other: ;possible fever.
Local reactions: pain at the injection site.
Drug interactions
When ketorolac is used concomitantly with other NSAIDs, additive side effects may develop; with pentoxifylline, anticoagulants (including heparin in low doses) - the risk of bleeding may increase; with ACE inhibitors - there may be an increased risk of developing renal dysfunction; with probenecid - the plasma concentration of ketorolac and its half-life increase; with lithium preparations - a decrease in the renal clearance of lithium and an increase in its concentration in plasma is possible; with furosemide - reducing its diuretic effect.
When using ketorolac, the need for the use of opioid analgesics for pain relief is reduced.
Preparation of aldehydes and ketones.
The most universal method is the oxidation of alcohols, in which aldehydes are formed from primary alcohols, and ketones from secondary alcohols (Fig. 9A and B). These are the opposite reactions to those in Fig. 7A and B. The reaction is reversed if the active reagent (oxidizing agent instead of the reducing agent) and the catalyst are changed; a copper catalyst is effective in the oxidation of alcohols.
In industry, acetaldehyde is obtained by the oxidation of ethylene (Fig. 9B); at the intermediate stage, an alcohol is formed in which the OH group is “adjacent” to the double bond (vinyl alcohol); such alcohols are unstable and immediately isomerize into carbonyl compounds. Another method is the catalytic hydration of acetylene (Fig. 9D), the intermediate compound being vinyl alcohol. If you take methyl acetylene instead of acetylene, you get acetone (Fig. 9E). The industrial method for producing acetone is the oxidation of cumene. Aromatic ketones, such as acetophenone, are produced by the catalytic addition of an acetyl group to an aromatic ring (Figure 9E).
