Claims:Finally, those skilled in the art may identify other equivalents to the particular embodiment mentioned that equivalents are intended to be encompassed by the claims attached below.
The invention claimed is:
1. A methodology of preparing amino acid diisocyanates, the methodology comprising of reacting amino acid diamines with triphosgene to form the amino acid diisocyanates, wherein the triphosgene was reacted with the ratio of 1:1.5 to the diamine in presence of a mild base at room temperature.
2. A methodology of preparing amino acid diisocyanates according to claim 1, wherein the amino acid diamines was obtained by deprotecting an amino acid diesters.
3. A methodology of preparing amino acid diisocyanates according to claim 2, wherein the N-protected amino acid diesters comprising of reacting N-protected amino acids with alkane diols.
4. A methodology of preparing amino acid diisocyanates according to claim 3, the N-protected amino acid diesters encompasses with the Formula I:

Formula I

Wherein R is –H or alkyl group; R1 is protecting group; n can be varied from 1 to 5.

5. A methodology of preparing amino acid diisocyanates according to claim 2, the amino acid diamines encompass with the Formula II:

Formula II
Wherein R is –H or alkyl group; n can be varied from 1 to 5.

6. A methodology of preparing amino acid diisocyanates according to claim 1, the amino acid diisocyanates encompass with the Formula III:

Formula III
Wherein R is –H or alkyl group; n can be varied from 1 to 5.
7. A methodology of preparing amino acid diisocyanates where the intermediary products can be reused as raw materials for PU synthesis via non-isocyanate pathway.
, Description:FIELD OF INVENTION

The current innovation narrates the development of a simple synthetic pathway to prepare a series of non-toxic diamines and diisocyanates monomers, key ingredients for producing biodegradable and biocompatible polyurethanes, from amino acids.

BACKGROUND OF THE PRESENT INVENTION

Over the years, polymer industry largely leans on raw fossil materials. The manufacturing of plastic materials totaled up to more than 360 million metric tons in 2018, unfortunately less than 1 wt% of the total production were produced from bio-based raw materials (Bio-Based Building Blocks and Polymers-Global Capacities, Production and Trends 2019–2024; Nova-Institute: Hurth, Germany, 2019). Recent times, tough environmental and legislative regulations along with economic factors are pushing the requirement for sustainable materials to a greater heights and thus bio-based materials technology has been expanding steadily. Biomass feedstocks are highly demanding resources as it is found to minimize the carbon footprint significantly and even their production process is expected to be more energy-efficient than petroleum-based plastics (J. Clean. Prod. 2012, 23, 47–56). These positive factors are the need of hour in order to reduce the global warming and climate change. In the recent years, a wide range of fully or partially bio-based plastics and resins have been documented by academics as well as industry bodies.

After discovery in 1937 by Otto Bayer, polyurethane (PU) always remains as one of the most highly demanding materials owing to their outstanding chemical, physical and mechanical properties including elasticity, durability, abrasive resistance, tensile strength. They are extensively used in variety of applications including thermal insulation for building and fridges, bed mattresses and pillows, shoe soles, scaffolds for tissue engineering, implants, automotive seats, fibers for textiles etc. Commercially, polyurethanes (PUs) are prepared in the form of rigid and flexible foams materials like thermoplastics, thermosets, elastomers, coatings, sealants or adhesives. Generally, PUs synthetic pathways are based on the polyaddition reaction of a diols / polyols with di-/poly-isocyanates. A variety of bio-based polyols are available in the market, also many are reported in various journals, but only a limited number of bio-based di/poly-isocyanates are mentioned in the literature with scarce commercial availability (J. Polym. Sci. Part. A Polym. Chem. 2010, 48, 3302–3310; Eur. J. Lipid Sci. Technol. 2010, 112, 10–30; Eur. Polym. J. 2013, 49, 823–833; U.S. Patent 3691225A, 1972). While the synthetic paths to bio-based diisocyanates is yet to be completely get rid of phosgene as a petroleum-based reagent, a handful of commercial diisocyanates with high renewable content are accessible in the market such as isocyanates based on fatty acids or amino acids. The low toxicity of the degraded products from amino acid-based products makes these diisocyanates most fascinating for the manufacturing of sustainable PUs. Although several synthetic roots exist now a days to prepare PU without employing isocyanates (non-isocyanate PUs), but slower reactivity is one of the major issues which need to be sort out by the researchers, at the same time, conventional PUs of industrial relevance are still in high demand on our daily life essence.

In the recent years, three different commercially available bio-based isocyanates are known and these are pentamethylene-diisocyanate (PDI) and its oligomers (e.g. PDI isocyanurate trimer from Covestro®), L-lysine ethyl ester diisocyanate (LDI) and Tolonate™ X FLO 100 based on HDI allophanate and palm oil from Vencorex® Chemicals (Mater. Express 2015, 5, 377–389; J. Polym. Mater. 2017, 34, 601–613). PDI isocyanurate and LDI are known to have maximal renewable carbon contents while Tolonate™ X FLO 100 is only partially bio-based. Amino acid based LDI has mainly been reported for biomedical applications such as drug delivery systems, implant materials, hydrogels, etc. (J. Biomed. Mater. Res. Part A 2011, 96A, 705–714.; J. Polym. Sci. Part A Polym. Chem. 1994, 32, 2345–2363; Polym. Chem. 2011, 2, 601–607). In a recent report, LDI was compared to petroleum-based hexamethylene diisocyanate (HDI), and isophorone diisocyanate (IPDI) in connection with reactivity and final properties of the PU and it was seen that LDI exhibited significantly higher reactivity than IPDI whereas almost similar to HDI besides few of their core PU properties were found to be enhanced considerably in case of LDI (Prog. Org. Coat. 2015, 86, 134–142). Detailed investigations on enzymatic breakdown/biodegradability of the above-mentioned bio-based PUs are carried out to demonstrate environmental friendliness of LDI based PUs (Chiang Mai J. Sci. 2018, 45, 2079–2091; Prog. Org. Coat. 2018, 123, 261–266; J. Polym. Environ. 2018, 26, 1818–1830; Mater. Sci. Eng. C Mater. Biol. Appl. 2018, 91, 426–435).

Notwithstanding, a simple, easy, efficient tools are still lacking in the literature (both in journal articles and patents) for designing new kind of bio-based polyurethanes building blocks and to pursue this there is a need for an advanced methods and compositions to make bio-based diamines and diisocyanates efficiently and safely. Herein, in this invention we are presenting a novel methodology to synthesize amino acid based diamines and diisocyanates in an effort to increase the availability of biocompatible monomers for polymer specially PUs market with the intention of diminishing the severe environmental pollution and toxicity effect associated with the non-biodegradable and non-biocompatible PUs to the end users.

DRAWBACKS OF KNOWN PRIOR ART:
Nowick et al. reported an improved method for the synthesis of enantiomerically pure amino acid ester isocyanate (J. Org. Chem. 1992,57, 7364-7366). In E.P. Pat. No. 1538143A1, Yamasaki et al. disclosed the synthesis of lysine ester triisocyanates which are useful in applications such as paint and processes for producing the same. In U.S. Pat. No. 9266824B2, Harrington et al. provided a method of making an amino acid triisocyanate - the method is comprising of reaction of an amino acid trihydrochloride salt with phosgene to form the amino acid triisocyanate. These are some of the known prior arts illustrating the synthesis of amino acid-based isocyanates that deals with certain drawbacks mentioned below:
1. Phosgene, a valued industrial reagent and building block in synthesis of pharmaceuticals and other organic compounds, is highly toxic in nature, this colorless gas gained infamy as a chemical weapon during World War I. In the known prior art, amino acid ester isocyanate involves continuous addition of a stream of gaseous phosgene into a refluxing suspension of amino acid ester hydrochloride over a period of several hours.
2. Described prior art required very high temperature to drive-off the hydrogen chloride byproduct and the harsh acidic reaction condition which limits the effectiveness as an established methodology.
3. As an alternate, described prior art proposed the addition of a commercially available solution of phosgene in toluene into the amino acid ester hydrochloride in presence of a base like pyridine to avoid the elevated temperatures and continuous addition of gaseous phosgene. Nevertheless, the use of phosgene solution in toluene, pyridine etc. are highly hazardous to handle.
4. Described prior art used phosgene in an amount of 5 to 15 equivalents to one amino group of the triamine or the salt thereof. This led to the excess of phosgene in the reaction medium which is again highly hazardous to handle.
5. Harrington et al. proposed a methods and compositions that can efficiently and safely generate phosgene. The described prior art used diphosegene and triphosgene as a phosgene substitute. The phosgene used was prepared by thermal and catalytic decomposition of di-/ tri-phosgene into phosgene so as to provide a phosgene source and then recovered in chlorobenzene or dichlorobenzene in liquid form. Despite the fact that in the said method phosgene can be recovered but these process deals with high risk of exposing of phosgene which is again highly hazardous.
6. Described prior art proposed by Harrington et al. delivered an alternate method of making di-/tri-hydrochloride salt from mono amino acid-based hydrochloride amine salt after treating with alkylalkanolamine and the related mono-/di-/-tri-isocyanate thereof. But the whole process requires vigorous work up procedure like extraction, separation, volatilization, and recrystallization and many more.
Considering the above drawback, there is a need of an improved and convenient synthetic process for the preparation of amino acid polyisocyanate.
In view of this, herein we have developed a simple and efficient synthetic process for the synthesis of diamines and diisocyanates from amino acid sources.

ADVANTAGES OF PRESENT INVENTION:
1. The current invention illustrates a convenient and cost-effective pathway to synthesize a series of amino acid-based diamines and diisocyanates.
2. According to known prior art mentioned earlier, amino acids having functionalized side chain can be easily converted to diisocyanates in contrary to those having no functionality at the side chain. The present invention proposed a novel methodology for the synthesis of diamines and diisocyanates from the amino acids having –H/ alkyl side chains. In fact, our suggested pathway can readily yield diamine and diisocyanate irrespective of amino acids structure and available functionality, it may need to go for an additional step to protect the functionality if required.
3. According to the embodiment of the present disclosure which will be discussed in the later section, the proposed methodology comprises of two intermediary step to obtain the desired diisocyanates and each of those intermediary products (diesters and diamines) can be utilized as a raw materials for synthesizing PU via non-isocyanate pathway.
4. The methodology used in the present disclosure can be easily scalable up to industrial scale.
5. All the organic reagents, solvents employed for the synthesis are easily available in the market at low cost.
6. Phosgene which is the core reagent to prepare diisocyanate used in the known prior art and requires extreme precautions during handling is not used here. Instead, the present invention employs triphosgene which is a safer substitute compared to phosgene. Triphosgene is a solid crystal with the decomposition temperature above 200 °C as opposed to phosgene which is gaseous in nature. Besides, the molar ratio of triphosgene to diamine was kept 1:1.5 so that in-situ generated phosgene can be completely used up to form diisocyanate.
7. The proposed methodology is associated with very easy work up and handling procedure. It consists of only three steps among which only once chromatographic separation is required. The resulting products were achieved with high purity having great yield via much easier purification process compared to existing methods.

OBJECTS OF THE PRESENT INVENTION

It is the object of the current invention to enclose a novel synthetic pathway for forming amino acid-based diamines and diisocyanates intending to increase the renewable content of biodegradable PUs.

It is another object of the current invention to outline a simple, cost effective, industrially scalable process for the synthesis of a series of amino acid based diamines and diisocyanates specially those amino acids having no additional functionality in the side chain such as Glycine, Alanine, Valine, Isoleucine.

It is an object of the current invention to provide a process for the synthesis of amino acid diisocyanate from amino acid diamine by employing triphosgene with a molar ratio of 1:1.5 to diamine at room temperature following very easy work up process.

It is another object of the current invention is the utility of each intermediary products as reagents for synthesizing PUs via non-isocyanate pathway.

SUMMARY OF THE PRESENT INVENTION

In short, the present invention demonstrates a simple, cost effective, efficient industrially scalable process for forming a series of amino acid-based diamines and diisocyanates comprising the steps of:

(a) preparing an amino acid diester treating commercially available N-protected amino acid with commercially available alkane diol at room temperature with the Formula I;

Formula I

Wherein R is –H or alkyl group; R1 is protecting group; n can be varied from 1 to 5.

(b) forming amino acid diamine comprises with diesters linkages encompasses with the Formula II;

Formula II
Wherein R is –H or alkyl group; n can be varied from 1 to 5.

(c) synthesizing amino acid diisocyanate by reacting amino acid diamine (Formula II) with triphosgene as a source of carbonylating agent at room temperature bearing Formula III;

Formula III
Wherein R is –H or alkyl group; n can be varied from 1 to 5.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1: Represents the 1H NMR spectra of decane diol-N-BOC-L-Isoleucine diester [DD-(N-BOC-L-IL)2] (I A).
Figure 2: Represents the 13C NMR spectra of decane diol N-BOC-L-Isoleucine diester [DD-(N-BOC-L-IL)2] (I A).
Figure 3: Represents the 1H NMR of decane diol isoleucine diamine [DD-(IL)2] (II A).
Figure 4: Represents the 13C NMR of decane diol isoleucine diamine [DD-(IL)2] (II A).
Figure 5: Represents the 1H NMR of decane diol isoleucine diisocyanate (DD-ILDI) (III A).
Figure 6: Represents the 13C NMR of decane diol isoleucine diisocyanate (DD-ILDI) (III A).
Figure 7: Represents a comparison of FT-IR spectra of DD-(N-BOC-L-IL)2, DD-(IL)2 and DD-ILDI.

DETAILED DESCRIPTION OF THE PRESENT INVENTION

The current invention outlines a simple and cost effective industrially viable process for the synthesis of a series of amino acid diamines and diisocyanates in order to make greener PUs. More precisely, the present invention allies with the preparation of alkyl side chain containing amino acid diisocyanate. This particular invention refers to the advancements in synthesizing amino acid diisocyanate compared to the existing methods; new compositions and methods are presented to make diisocyanates safely and efficiently.
In one embodiment, there is an approach for preparing amino acid based diesters, the methodology comprising reacting N-protected amino acid with alkane diol to produce amino acid containing diester.
In another embodiment, there is a method of making amino acid-based diamines, the step encompassing a deprotection of amino acid functionality.
In other embodiment, there is a pathway of forming amino acid based diisocyanates by treating the diamines with triphosgene at room temperature.
Amino acid based diester preparation
The composition and method of making amino acid based diester include selecting a commercially available N-protected amino acid and treating with commercially available alkane diol in presence of a suitable coupling agent. Protected amino acids useful to make the related diesters include glycine (Gly), alanine (Ala), valine (Val) and isoleucine (IL). Suitable alkane diols include 1, 10-decane diol (DD), hexane diol (HD) and ethylene glycol (EG).
In one embodiment of the present invention, providing the compound with Formula I:

Formula I

Wherein R is –H or alkyl group; R1 is protecting group; n can be varied from 1 to 5.
Some of the protected forms of amino acid that can be used in the present disclosure comprises of those that do not substantially increase the toxicity of the compound, for example, suitable amine protecting groups of an amino acid like tert-butyloxycarbonyl (Boc), 9-fluorenylmethoxycarbonyl (Fmoc), benzyloxycarbonyl (Cbz/z), allyloxycarbonyl (Alloc).
The N protected amino acid is reacted with alkane diol in presence of a coupling agent to form amino acid diesters. Well suited coupling agent include carbodiimide based dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC) or ethyl-(N', N'-dimethylamino)propylcarbodiimide hydrochloride (EDC. HCl) in addition with additives like 4-(N,N-dimethylamino)pyridine (DMAP) or 1-hydroxybenzotriazole (HOBt) to minimize the undesirable levels of racemization.

According to the embodiment of the current invention, the reactants including N protected amino acid and alkane diol are reacted together in a single reaction vessel with the molar ratio of 2.2:1. The N protected amino acid can be added to the alkane diol or the alkane diol can be added to N protected amino acid, any either of these can take place in a medium of an appropriate organic solvent in addition with a coupling agent. In some embodiment, the alkane diol can be in solid or in liquid form and can be added to the solid form of N protected amino acid at room temperature.
According to the embodiment, an organic base can be added include triethyl amine, diethyl amine or pyridine in an ice-cold condition. Presence of an organic base can help to neutralize the reaction medium. According to the embodiment, the reaction can be stirred up to 12 h to 24 h after addition of the organic bases at room temperature.
According to the embodiment, the amino acid diesters can be purified with the separation of in situ formed insoluble byproduct via filtration followed by acid base work up which makes the purification steps further easier. The amino acid diesters can be isolated and purified by filtration, extraction, solvent evaporation and chromatography process that separates non-volatile solutes, impurities as well as side products with the yield of 80% to 85%.
In some embodiments, the diester can be appeared as a colorless or light green or light yellowish viscous liquid; in some embodiments it can be appeared as a viscous liquid that slowly converting to amorphous solid.
According to the embodiment, some useful amino acid diesters encompass decane diol-glycine-diester, decane diol-alanine-diester, decane diol-valine-diester, decane diol-isoleucine-diester, hexane diol-valine-diester, hexane diol-isoleucine-diester, ethylene glycol-valine-diester and ethylene glycol-isoleucine-diester.

Amino acid based diamine preparation
In another embodiment, the present disclosure provides a one step process for the formation of amino acid diamine, an intermediary for the production of amino acid diisocyanate. According to the embodiment, the amino acid diamine comprises of the Formula II:

Formula II
Wherein R is –H or alkyl group; n can be varied from 1 to 5.
The method of preparation of the diamine are performed in a single pot reaction vessel by reacting protected amino acid diester with readily available reagent like a suitable deprotecting agent. Some of the well-known deprotecting agent which can be useful for the current invention include trifluoroacetic acid (TFA), trimethylsilyl chloride (TMS-Cl)-phenol, methanesulfonic acid (MeSO3H), piperidine, Pd/ C catalyst, tetrakis(triphenylphosphine)palladium [Pd(PPh3)4].
The optimized condition was developed for this embodiment of the invention comprising the use of previously prepared protected amino acid diester for example decane diol-protected-isoleucine-diester and a deprotecting agent for example TFA with a molar ratio of 1:20 in a medium of a chlorinated solvent. The addition of the reagents was chosen to add in an ice-cold condition to suppress the possibility of increment in temperature in an exothermic reaction and stirred for 2 h at room temperature.
According to the embodiment, the desired amino acid diamines can be purified and isolated very easily simply via solvent extraction and evaporation with the yield of 95% to 98%.
In most of the embodiment the desired diamines appear as a light yellowish oil but in some of the embodiment it can be light greenish oil or can be light greenish free flowing solid powder or else can be light yellow oil which slowly converting to solid.
According to the embodiment, the synthesized diamines include decane diol-glycine-diamine, decane diol-alanine-diamine, decane diol-valine-diamine, decane diol-isoleucine-diamine, hexane diol-valine-diamine, hexane diol-isoleucine-diamine, ethylene glycol-valine-diamine and ethylene glycol-isoleucine-diamine.

Method of making amino acid based diisocyanate
According to this embodiment of the present disclosure, the compositions and methodology of preparing amino acid based diisocyanates include making an amino acid diamine first and then using these diamines to synthesize corresponding diisocyanates. In the previous embodiments, the method of making amino acid diamines is depicted and, in this embodiment, here is a pathway of making amino acid diisocyanates, the method comprising reacting amino acid based diamine with triphosgene a "phosgene equivalents" as carbonylating agent. According to the embodiment, the amino acid diisocyanate comprises of the Formula III.

Formula III
Wherein R is –H or alkyl group; n can be varied from 1 to 5.
Once the reagents like diamine and base were combined in a medium of suitable organic solvent, in this embodiment, triphosgene was added with the molar ratio of 1:1.5 to diamine in single portion at ice cold condition. After reaction mixture was brought to the room temperature it was continuously stirring upto 12 hours.
According to the embodiment, the reaction were performed in presence of a mild base that can help to drive off hydrogen chloride by product of the reaction. Some of the useful mild base that can be considered herein include aqueous saturated sodium bicarbonate (NaHCO3) solution, very dilute aqueous solution of sodium hydroxide/ potassium hydroxide/ ammonium hydroxide.
According to the embodiment, the current disclosure uses triphosgene and a mild base to minimize the toxicity and hazard of the reagents handling and waste products. This mild reaction condition is superior as compared to alternate methods for preparing amino acid polyisocyanates that encompasses with refluxing amino acid precursor in toluene with continuous purging of gaseous phosgene for several hours (Ann. Chem. 1952, 575, 217-231) or treating amino acid precursor with di-tert-butyl-dicarbonate and 4-dimethylaminopyridine (DMAP) (Synlett 1997, 925-928) or else treating triphosgene/ phosgene as mentioned in the known prior art in earlier section of this invention (J. Org. Chem. 1992,57, 7364-7366; E.P. Pat. No. 1538143A1; U.S. Pat. No. 9266824B2). Moreover, triphosgene was added in low quantity in the feed stock with respect to diamine considering the fact of total consumption of triphosgene as a carbonylating agent to form diisocyanate.
The optimized condition was developed in this embodiment encompassing reacting amino acid diamine for example decane diol-isoleucine-diamine and a mild base like aqueous saturated solution of sodium bicarbonate with triphosgene with a molar ratio of 1: 1.5 (triphosgene to diamine) in a medium of a chlorinated solvent.
According to this embodiment, amino acid diisocyanates were produced very easily without having any exhaustive purification step, this method involves with simple work up process like extraction and concentration of the reaction mixture. The products were purified to analytical purity simply via Kugelrohr distillation with the yield of 65% to 70%. All the purified products appeared as a colorless liquid.

According to the embodiment, the amino acid diisocyanates include decane diol-glycine-diisocyanate, decane diol-alanine-diisocyanate, decane diol-valine-diisocyanate, decane diol-isoleucine-diisocyanate, hexane diol-valine-diisocyante, hexane diol-isoleucine-diisocyanate, ethylene glycol-valine-diisocyanate and ethylene glycol-isoleucine-diisocyanate.
Thus the proposed methodology herein for the synthesis of amino acid diisocyanates is simpler in terms of cost and operation which can be easily scaled up at industrial scale.

Even though the present invention has been embodied as many different compositions as described above, all the compositions demonstrated are an exemplification of the fundamentals of the inventions and is not intended to limit the scopes of the invention.
The basic aspects of the invention are described in the examples below:

EXAMPLES

EXAMPLE 1: Synthesis of 1, 10-decane diol-N-BOC-L-Isoleucine diester [DD-(N-BOC-L-IL)2] (I A):

A mixture of 1,10-decanediol (10.0 g, 57.40 mmol), N-BOC-L-Isoleucine (29.18 g, 126.280 mmol), EDC.HCL (26.4 g, 137.76 mmol) and HOBt (18.6 g, 137.76 mmol) in THF (200 mL) was stirred at room temperature for about 10 min under nitrogen atmosphere. Triethylamine (40 mL, 287.00 mmol) was added drop wise to the reaction mixture in an ice-cold condition. After the addition, the mixture was allowed to stir further for 24 hours at room temperature to complete the reaction and monitored by TLC. The separated solid urea was then filtered. The filtrate was dried under reduced pressure. The crude viscous liquid was dissolved in ethyl acetate (150 mL) and washed with 0.2M citric acid solution (2 x 150 mL) followed by saturated NaHCO3 solution, brine solution and finally with Millipore water (2 x 150 mL). Anhydrous Na2SO4 was added of to this liquid as a drying agent and the solution was concentrated. The crude mixture was purified by column chromatography. Yield: 85%
1H NMR (400 MHz, CDCl3, d ppm): 5.0 (2H, d, NH) 4.24 (2H, d, CH-NH), 4.12 (4H, t, O-CH2) 1.83 (2H, m, HC(CH3)-CH2-CH3) 1.55 (4H, m, CH2), 1.39 (18H, s, C(CH3)2), 1.25 (12H,m,(CH2)6), 1.1 (2H, m, (CH2), 0.85(12H, d&t CH3,CH2CH3); 13C NMR (100 MHz, CDCl3, d ppm): 172.4, 155.5, 79.5, 64.8, 57.9, 38.1, 30.1, 29.7, 29.3, 28.6, 26.3, 25.1, 15.5, 12.; HRMS: calculated for C32H61N2O8: 601.4428 [M+H]+, found: 601.4426 [M+H]+.; FT-IR (cm-1): 3382, 1714, 1744, 2854, 2933, 2981.

EXAMPLE 2: Synthesis of 1, 10-decane diol isoleucine diamine [DD-(IL)2] (II A):
Diester, IA (5.8 g, 9.66 mmol) was dissolved in 100 mL of dichloromethane and then added of trifluoroacetic acid (14.7 mL, 193.4 mmol) drop wise using pressure equalized funnel under cold condition. After the addition, stirring was continued for another 2 h at room temperature. Then, the reaction mixture was neutralized with ice-cold saturated aqueous sodium bicarbonate solution followed by separation of the organic layer. The aqueous layer was again extracted using dichloromethane (1x100 mL). The combined organic phases were washed with brine and Millipore water (2 x 150 mL). Anhydrous Na2SO4 was added as a drying agent and the solvent was removed under reduced pressure. The product was used without further purification. Yield: 98%
1H NMR (400 MHz, CDCl3, d ppm): 4.09 (4H, t, O-CH2) 3.33 (2H, d, CH-CO) 1.73 ( 2H, m, HC-(CH3)-CH2-CH3) 1.65 (4H, m, CH2-CH2-O) 1.53 (4H, s, NH2-CH) 1.38 (4H, m, CH2-CH3) 1.20 (4H, m, CH2-(CH2) 2) 0.83-0.96 (12H, d of d, (CH3) 2-CH); 13C NMR (100 MHz, CDCl3, d ppm): 175.2, 64.2, 58.5, 36.8, 29.4, 29.1, 28.8, 25.6, 25.1, 15.3, 12.3. HRMS: calculated for C22H45N2O4 [M+H]+· 401.3379, found: 401.3378. FT-IR (cm-1): 1602, 1730, 2854, 2933, 2975, 3319, 3390.
EXAMPLE 3: Synthesis of 1, 10-decane diol isoleucine diisocyanate (DD-ILDI) (III A):
Diamine [DD(IL)2], IIA (4.39 g, 10.97 mmol) was taken into a round bottom flask and dissolved in 100 mL of chloroform. To this, 100 mL of saturated aqueous sodium bicarbonate solution was added. After 10 minutes of stirring, triphosgene (2.19 g, 7.3 mmol) dissolved in 30 mL of chloroform was added under ice cold conditions. Slowly the reaction mixture was brought to room temperature and continued stirring at this temperature for 12 hours. Then the reaction mixture was extracted with chloroform and washed with brine solution followed by Millipore water, dried using anhydrous sodium sulfate and concentrated to remove solvents under reduced pressure. The crude diisocyanate was distilled using Kugelrohr apparatus to obtain a pure diisocyanate as colorless liquid. Yield: 70%
1H NMR (400 MHz, CDCl3, d ppm): 4.23 (4H, m, O-CH2), 3.92 (2H, d, H-C-N), 1.98 (2H, m, H-C(CH3)(CH2CH3)), 1.70 (4H, m, H2C-CH2-CH3), 1.23-1.41 (16H, m, CH2), 0.83-1.05 (12H, d,t, CH3). 13C NMR (100 MHz, CDCl3, d ppm): 171.1, 126.9, 66.4, 62.9, 38.6, 29.4, 29.1, 28.5, 25.7, 24.3, 16.4, 11.5. HRMS: calculated for C24H44N3O6 [M+NH4]+· 470.3230, found: 470.3246. FT-IR (cm-1): 1730, 2254, 2854, 2933, 2975.