(12) Patent Application Publication (10) Pub. No.: US 2007/0128680 A1 Lopes Et Al
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US 2007.0128680A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/0128680 A1 Lopes et al. (43) Pub. Date: Jun. 7, 2007 (54) HYDRAZINES AND DERVATIVES (30) Foreign Application Priority Data PRODUCTION PROCESS FROM HYDRAZINES AND DICARBOXYLIC ACID Nov. 25, 2003 (BR)...................................... PIO3O7864-7 (76) Inventors: Claudio Cerqueira Lopes, Del Publication Classification Castilho (BR); Rosangela Sabattini Capella Lopes, Rio de Janeiro (BR): (51) Int. Cl. Jari Nobrega Cardoso, Rio de Janeiro CI2O I/66 (2006.01) (BR); Jacqueline Alves da Silva, Rio C07D 237/28 (2006.01) de Janeiro (BR); Leticia Gomes Ferreira, Rio de Janeiro (BR) (52) U.S. Cl. .............................. 435/8; 544/235; 564/148; 564/149 Correspondence Address: POWELL GOLDSTEIN LLP ONE ATLANTC CENTER (57) ABSTRACT FOURTEENTH FLOOR 1201 WEST PEACHTREE STREET NW ATLANTA, GA 30309-3488 (US) The present invention describes a process to form hydrazides from the reaction of a hydrazine and a dicar (21) Appl. No.: 10/595,943 boxylic, using a Lewis acid as a main reagent of the reaction. The reaction occurs in a safe reactional environment, ulti (22) PCT Filed: Nov. 25, 2004 lizing Smooth conditions, neither involving high tempera (86) PCT No.: PCT/BRO4/OO236 tures nor high pressures, producing the desired products with high yields, between 90-95%. The invention also S 371(c)(1), describes a kit for utilization of chemiluminescent sub (2), (4) Date: May 22, 2006 stances, comprised of two solutions. US 2007/0128680 A1 Jun. 7, 2007 HYDRAZINES AND DERVATIVES PRODUCTION 0005 There are many applications for chemiluminescent PROCESS FROM HYDRAZINES AND substances besides forensics. Recently, there has been a DCARBOXYLIC ACID demand and production increase, especially for entertain ment and in accidents preventions industries. A number of FIELD OF THE INVENTION accessories, such as bracelets, necklaces, earrings, plastic 0001. The present invention describes a new process that teeth frame, cups etc., are frequently used in events, resi favors the production of hydrazides from dicarboxylic acids, dences, night clubs, theaters, stadiums, music festivals, using a Lewis acid. More specifically, the present invention rodeos and many others, drawing the attention of the public is directed to the formation of phtalazides, for example with the intense chemiluminescence reaction glow. Safety luminol, using as Lewis acid a halide donator, more spe flares are used by scuba-divers in deep waters and poor cifically chloride, for example niobium pentachloride. The visibility, especially in the maintenance of underwater process provides a global yielding well above traditional industrial petrol plants maintenance, or by the police and fire techniques yielding, as well as easy execution, without the department in case of night accidents with intense fog or in need of drastic reactional conditions. unfavorable weather conditions on roads and large avenues or by the coast guard, helping night sailing on rivers, bays BACKGROUND OF THE INVENTION and near the coast. These are some examples of the many 0002. It is extremely desirable and convenient to have applications of the chemiluminescent Substances industrially secure methods for the reliable trace detection of substances produced by the process described on the present invention, in liquids, especially body fluids, where the presence of a specially the luminol. concentration as low as 10' M of a substance may be 0006 Luminol and its derivatives synthesis process potentially pathogenic. include, among other steps, the reaction of a dicarboxylic 0003 Classical methods of detection in liquids are based acid with a hydrazine. This stage is usually difficult to on reaction mechanisms where either the appearance of a accomplish, since drastic conditions are needed and the product or the disappearance of a reagent can be measured. yield is not significantly high. Some documents propose Greater importance is given to chemiluminescent com Solutions to this stage. pounds, capable of producing light when in favorable con 0007 British patent GB 1,100,911 is the first to describe ditions. the synthesis of phtalazine derivatives. Among the proposed 0004 The chemiluminescence is a method based on processes, it uses a mixture of a dicarboxylic acid and a certain Substances characteristic of emitting light when in hydrazine, the mixture being heated under reflux for 4 hours. presence of the compound to be analyzed. It has applications The solution is cooled and water and HCl are added until pH in forensics, diagnosis and quality control fields, being 7. The solid formed is recrystallized in hot water. capable of detecting traces of compounds. One example of 0008 American patent U.S. Pat. No. 4,226,992 performs a commonly used chemiluminescent Substance in criminal the formation of the phtalazide from a dicarboxylic acid and investigations is luminol, capable of detecting blood stains a hydrazine in methanol under reflux for 3 hours. After hidden in Suspicious locations, such as crime scenes. The cooling, the mixture is evaporated until dryness in a roto mechanism of action of luminol is based on the reaction evaporator, and the crystalline residue dried overnight at 80° below, where the addition of hydrogen peroxide is capable C. under vacuum. of oxidizing the luminol in a basic medium, generating light. 0009 American patent U.S. Pat. No. 4.226,993 describes However, the reaction below needs a catalyst, which will be the reaction of a phtalimide with a hydrazine, in ethanol for the iron (Fe) present on erythrocyte's hemoglobin of the 2 hours under reflux, followed by cooling and rest overnight. blood. Hence, when a basic luminol Solution is put in contact After evaporation in rotoevaporator under reduced pressure, with a hydrogen peroxide Solution with Fe, an intense glow the solid was dried at 110° C. for 8 hours under a pressure will be produced, confirming the presence of the compound. of 0.1 mmHg. The solid residue was stirred for 90 minutes O O Oo O H N1 N- e- N. O.". O re- | - 2 - + hv + N2 N n N n ) N O H H H+ NH O NH O NH2 O NH O US 2007/0128680 A1 Jun. 7, 2007 in HCl 10%, filtered and neutralized with KOH, and the DETAILED DESCRIPTION OF THE precipitated was filtered, dried and recrystallized in aqueous INVENTION dimethyl formamide 0020. The present invention presents innovative charac 0010. One document describing a technique similar to the teristics in an alternative process for hydrazide production, present inventions is American patent U.S. Pat. No. 6,489, based in the use of halide donors as catalysts, resulting in 326. It describes an extremely dangerous and complex reactions with better yields than the available methods. The production process of a hydrazide from the 3-nitro-phtalic present invention also provides a new process of luminol anhydride and hydrazine. In spite of presenting excellent synthesis which is cheaper and economically viable. yields, between 85 and 90%, the reaction involves a Ni 0021. The reaction described aims a production of a Raney catalyst, gas generation, such as N2 and H, and is hydrazide from the reaction of a dicarboxylic acid of a extremely exothermic, reaching temperatures of 285-90° C. general formula (I): 0011 Unlike all the processes described above, the present invention uses a halide donator, more specifically (RCH), (COOH), (I) chloride, even more specifically niobium pentachloride in wherein R1 can be hydrogen, alkyl, alkenyl, alkinyl, phenyl, dioxane, that promotes a Smooth reaction, easy controlled aromatic heterocyclic ring containing as heteroatom S. O and capable of generating 90-95% yield. and/or N. heterocyclic non-aromatic ring containing as het eroatom S. O and/or N. cycloalkyl containing from 3 to 8 0012 Niobium pentachloride is a known Lewis acid, carbon atoms, cycloalkenyl containing from 3 to 8 carbon used as a catalyst for cyclotrimetrization reactions, for atoms, cycloalkinyl containing from 3 to 8 carbon atoms; all example, reactions described in document WO 91/09066. the described groups can be further substituted and/or Regarding the synthesis of organic compounds, an important branched; document, though not relevant, is document U.S. Pat. No. 4.349,471, which describes the synthesis of sulfonic acid 0022 in varies from 1 to 2: halides and aromatic carboxylic acids halides. The referred 0023 with a hydrazine of general formula (II): reaction involves the use of a Lewis acid, for example niobium pentachloride. 0013 However, the reaction of the present invention is (II) completely different from the reactions described on the above mentioned documents, and therefore the use of a Lewis acid halide donator, more specifically chloride, for example niobium pentachloride, aiming hydrazides synthe sis from dicarboxylic acids and hydrazines have never been described before, being the present invention therefore new. wherein R2 and R3 are, independently, hydrogen, alkyl, alkenyl, alkinyl, phenyl, heterocyclic aromatics contain OBJECT OF THE INVENTION ing as heteroatom S. O and/or N. heterocyclic non 0014. It is an object of the present invention to provide an aromatics containing as heteroatom S. O and/or N. alternative process for the synthesis of hydrazides from cycloalkyl containing from 3 to 8 carbon atoms, cycloalk dicarboxylic acids and hydrazines. enyl containing from 3 to 8 carbon atoms, cycloalkinyl containing from 3 to 8 carbon atoms; 0015. It is an additional object of the present invention to provide a process for the synthesis of hydrazides in safe and 0024 in the presence of a chloride donor reagent. Smooth reactional conditions, without gas or heat liberation 0025 Additionally, the present invention aims the pro and having an excellent yield. duction of a hydrazide from the reaction of a dicarboxylic 0016. It is still an object of the invention to provide acid of general formula (III): economically more viable hydrazides synthesis. 0017. It is an object of the present invention to provide a (III) process of synthesis of hydrazides, where such process is O based on the use of a Lewis acid as a halide donator.